pharm. practice exam questions- exam 2

Question 1

what is a disperse system?

what does a dispersed system have

Answer 1

a liquid preparation with undissolved (or immiscible) drug substance distributed throughout the vehicle (medium in which the drug is administered)

a dispersed system both has a dispersed phase and a continuous phase

Question 2

what is a dispersed phase?

what is a continuous phase?

Answer 2

dispersed phase: the distributed substance (the drug)

continuous phase: the vehicle (medium) medium that supports the dispersed phase

Question 3

what is the range of sizes and categories that a dispersed system comes in

Answer 3

colloidal dimensions: 1.0nm to 0.5 um

fine dispersions: 0.5um to 10um

coarse particles: 10um to 50um

Question 4

compared to fine dispersions, what do coarse particles do

Answer 4

they have a tendency to separate from the dispersion medium

Question 5

solids generally do what in a dispersed system, what is the reason for this

what do emulsified liquids do in dispersed systems, why is that

Answer 5

solids generally settle to the bottom of the container because they are denser than the dispersed medium

emulsified liquids (like oil) tend to float to the top because they have a lower density and thus are lighter

Question 6

why is light agitation of the preparations necessary for dispersed systems

Answer 6

to ensure that the dispersed phase is uniformly spread through the continuous phase. Need to move homogenously regardless if solid or liquid

Question 7

what is a suspension?

Answer 7

a powdered mixture of drugs with sufficient suspending and dispersing agents to be diluted (and agitated) with a vehicle

Question 8

how does a pharmacist prepare an antibiotic and why

Answer 8

because antibiotics are unstable in aqueous solutions for a long period of time, a pharmacist should reconstitute them before giving them to the patient

antibiotics usually come as powders and are mixed with water before being given to patient

Question 9

what does reconstitute mean

Answer 9

add solvent or diluent to a medication in powdered form to form a solution

Question 10

when do you reconstitute

Answer 10

when designated in USP by the title “for oral suspension”

prepared suspension not requiring reconstitution at the time of dispensing is designated as “oral suspension”

Question 11

why are pharmaceutical suspensions made?

how is the third option done?

what is erythromycin estolate

Answer 11

• when drugs are chemically unstable in solution but stable in suspension
• when a patient has an issue swallowing and prefers liquid dosage forms
• to mask the disagreeable or unpleasant taste that comes from the drug. Can do so by adding flavorants to the continuous phase (has to be soluble in water/vehicle because the continuous phase comes into contact with the taste buds

Erythromycin estolate
- Less water-soluble ester form of erythromycin
- Used to prepare a palatable (pleasant taste) liquid dosage form of erythromycin.
- Erythromycin Estolate Oral Suspension, USP.

Question 12

what are general things to consider for preparing drugs?

Answer 12

• therapeutic efficacy
• chemical stability of the components of the formulation
• esthetic appeal

Question 13

what are the Specific things to consider for pharmaceutical suspensions keep in mind

Answer 13

• rate of settling - should be slow and readily dispersed upon gentle shaking, particles redistribute and do not settle too fast
• particle size - remains constant through long periods of undisturbed standing
• the suspension should pour evenly from the container, happens if you do not get aggregation

Question 14

in Specific things to consider for pharmaceutical suspensions, what should we consider for rate of settling

Answer 14

• rate of settling - should be slow and readily dispersed upon gentle shaking, particles redistribute and do not settle too fast

Question 15

in Specific things to consider for pharmaceutical suspensions, what should we consider for particle size -

Answer 15

particle size - remains constant through long periods of undisturbed standing

Question 16

in Specific things to consider for pharmaceutical suspensions, what should we consider for the suspension

Answer 16

the suspension should pour evenly from the container, happens if you do not get aggregation

Question 17

what does the Stokes equation represent

what are the variables and what do they mean

Answer 17

represents the Sedimentation Rate of the Particles of a Suspension

V = Rate of particle settling

d = Diameter of particle

Pi = Density of particle

Pe = Density of medium

g = Gravitational constant

n = Viscosity of medium

V = (dx/dt) = ((d^2 (pi - pe)g)/18 n

Question 18

what can result in the greatest change in the rate of particles settling in the Influence of dispersion medium on particle settling

Answer 18

Changing the dispersion medium can result in the greatest change in the rate of particle settling.

Question 19

what can contribute to suspension stability in Influence of dispersion medium on particle settling

Answer 19

Particle size reduction also can contribute significantly to suspension stability.

Question 20

to increase the rate of settling
would you Increase or Decrease the diameter or size of the particle

Answer 20

increase
larger particles sink faster

Question 21

to increase the rate of settling
would you Increase or Decrease the the density of the particle

Answer 21

increase
denser/heavier particles sink faster

Question 22

to increase the rate of settling
would you Increase or Decrease the density of the medium

Answer 22

decrease
particles move slower in denser mediums

Question 23

to increase the rate of settling
would you Increase or Decrease the viscosity of the medium

Answer 23

decrease
particles move slower in more viscose mediums

Question 24

what was Stokes’ law derived for

describe this_____

Answer 24

an ideal situation:
particles are
- uniform
- perfectly spherical
- without turbulence
- without physical contact between the particles or particle affinity for the vehicle (medium)

Question 25

Is Stokes’ ideal situation realistic?

why or why not

what does Stokes’ law allow for

Answer 25

no, it is not!

Because particles are
- not necessarily uniform
- are irregularly shaped
- particle settling results in turbulence and collisions.

Stokes law does allow
- formulation experts to determine the formulation features that can be changed to achieve an elegant and desired finished product.

Question 26

what is generally the size of particles in dispersed phase

Answer 26

1 to 50 μm

Question 27

what does the reduction in particle size cause particles in the dispersed phase to do settling

what happens if the particle size is too small

what does it result in

Answer 27

Reduction in particle size produces slow and more uniform settling, but not too small.

If too small, a compact cake could form.

Compact cakes are difficult to break up with shaking

Question 28

what can affect the stability of a dispersed phase?

what are the two things

Answer 28

The particle shape of the suspensoid can affect the stability

Needle shape versus barrel-shaped particles

Question 29

what do needle-shaped particles do in the dispersed phase?

Answer 29

: form strong sediment cake on standing that can’t be disturbed upon gentle shaking

Question 30

what do barrel-shaped particles do in the dispersed phase

Answer 30

do not cake on standing at all

Question 31

what can you use a floc or floccule for

Answer 31

Consider preventing particle agglomeration into crystals or some larger particulate mass of the dispersed phase by using a floc (or floccule)

Question 32

what is agglomeration

Answer 32

a mass or collection of things

Question 33

what do flocculated particles form

what do floc and non-flocculated particles form

what can be said about the agitation of flocculated particles?

Answer 33

form a type of lattice that do not completely settle.

The ‘flocs’ settle to form a higher sediment volume than non-flocculated particles.

The flocculated particles break up easily with a gentle amount of shaking.

Question 34

what about settling is not ideal

what can be used to prevent this and what is an example of this

once the sus. agent has been determined, what must be done to ensure what

Answer 34

• Rapid settling is not ideal,
• Suspending agents (i.e., carboxymethyl cellulose- CMC, methylcellulose, bentonite) are used to thicken the medium to suspend the suspensoid.

Once suspending agent has been determined, tests must be performed to be certain that agent does not interfere with drug availability.

Question 35

what is a suspensoid

Answer 35

a system consisting of a suspension of solid particles in a liquid.

Question 36

how much of the suspending agent be used

Answer 36

enough and should not make suspension too viscous
- because these are too difficult to pour.

Question 37

Whether or not to use a suspending agent depends on what factors,

Answer 37

Density of the suspensoid

Amount of material requiring support

Whether it is flocculated

Question 38

when preparing suspensions what should pharmacists be aware of

Answer 38

relationship between the dispersed phase and continuous phase

Question 39

what may the dispersed phase have an affinity for

Answer 39

dispersed medium (vehicle) and is therefore wetted by it.

Question 40

when does the dispersed phase clump and what is done in this situation?

Answer 40

when dispersed materials lack any affinity for the medium they clump together or float on the vehicle– In this case, wetting agents like hydroscopic agent are employed like
- Alcohol Glycerin,
- Propylene glycol

Question 41

how do hydroscopic agents work

what can also be added to the continuous phase of the suspension?

Answer 41

Displace air in crevices of the particles, permitting dispersed medium to penetrate the particle

Preservatives should also be added when possible to safeguard against microbial and mold growth.

Question 42

what are examples of oral suspensions?

Answer 42

Antacid oral suspensions

Antibacterial oral suspensions

Rectal suspensions

Dry powders for suspensions

Question 43

what are antacid oral suspensions intended for

how are antacds avaible to patients

Answer 43

Intended to combat the effects of gastric hyperactivity (i.e., peptic ulcers of the stomach).

Many OTC medications are available for the treatment of patients with gastric indigestions, or to counter acid reflux to the esophagus and throat

Question 44

what are most antacid preparations composed on

where does it act

what is the result

Answer 44

water-insoluble material acting within gastrointestinal tract, soothing the irritated or inflamed linings of GI tract.

Question 45

for antacids what does the Ability to neutralize acid effect depend on

Answer 45

Ability to neutralize acid effects vary according to the chemical reagents employed

Question 46

what are the 4 problems with antacid oral suspensions

Answer 46

Sodium bicarbonate (SB):

Magnesium preparations (MP):

Calcium carbonate:

Aluminum hydroxide:

Question 47

for antacids what is the problem with SB and what does it do well

Answer 47

Neutralizes acid effectively.
However, can produce sodium overload and systemic alkalosis.

Question 48

for antacids what is the problem with MP

Answer 48

Neutralizes acid effectively.
However, can cause diarrhea and cause problems for patients with renal impaired function.

Question 49

for antacids what is the problem with Calcium carbonate

Answer 49

Neutralizes acid effectively.
However, can also cause hypercalcemia and stimulation of acid secretion (acid rebound).

Question 50

for antacids what is the problem with Aluminum hydroxide:

Answer 50

Neutralizes effects slowly, and not as well as SB or MP.
However, excessive use may lead to constipation and phosphate depletion, resulting in muscle weakness, bone resorption and hypercalciuria

Question 51

Why do liquid suspensions provide more immediate action than solids?

Answer 51

absorb faster

Question 52

how must antacids act

Answer 52

Must be reasonably fast acting since gastric emptying is rapid (~1 hr in fasting stomach following administration).

Question 53

how long does the FDA. require liquid antacids to disintegrate

Answer 53

within 10 minutes of simulation gastric conditions.

Question 54

Since antacids such as calcium-containing products interfere with the absorption of other drugs ((i.e., fluoroquinolone, tetracycline antibiotics, iron salts)
what must pharmacists consider

Answer 54

Pharmacists must caution patients against taking such drugs concomitantly (together)

so caution against taking calcium-containing drug with antacid

Question 55

what is barium sulfate, USP

Answer 55

a suspension that can be administered rectally or orally for diagnostic visualization of GI tract. Do not confuse with sulfite

Question 56

What do antibiotics represent

Answer 56

for oral suspensions, Antibiotics represent the majority of drugs prepared as a dry mix.

Question 57

what do antibiotic preparations contain

Answer 57

The antibiotic drug,

colorants

flavorants

Sweeteners, (e.g.,sucrose, dextrose)

Stabilizing agents (e.g., citric acid)

Suspending agents (e.g., methylcellulose)

Preserving agents (e.g., methylparaben, sodium benzoate)
where the water is where contamination could happen

All of these excipients must be soluble in the continuous phase—which come into contact with sweeteners

Question 58

when should purified water be used and what does it prevent?

Answer 58

During reconstitution of dry powder or granules, the use of purified water (rather than tap water) will prevent the possibility of any impurities from affecting stability of the preparation.

Question 59

what sized containers should pharmacists use during reconstitution

should the amount of water be estimated

Answer 59

Pharmacists must realize that oversized containers are to be used to allow for adequate shaking after purified water has been added.– do not want to fill up so much but leave room to be able to shake

Note: The amount of water to be added should not be estimated, but should be carefully measured for accuracy. Too much or too little must be avoided.

Question 60

what other official drugs are intended for use as an oral suspension

Answer 60

Cholestyramine (Questran, Par)- for treatment of hyperlipidemia,

Barium Sulfate (Barospere, Mallinckrodt)- for visualization of the gastrointestinal tract, used orally or rectally.

Question 61

what is an emulsion

Answer 61

“A dispersion in which the dispersed phase is Composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible”– going to globules, oils, vary in size range

Question 62

what is the external phase of an emulsion

how may an o/w emulsion be diluted

Answer 62

Since the external phase of an emulsion is continuous

an o/w emulsion may be diluted (or extended) with water or some other aqueous preparation. Similarly, in w/o emulsion it may be diluted with oil-miscible liquid.

Question 63

Many _____ preparations that are really _____ are not classified as such, because they fit another _____ more appropriately. For e.g., Certain ____, creams, ____, commercial vitamin drops

Answer 63

Many pharmaceutical preparations that are really emulsions are not classified as such, because they fit another category more appropriately. For e.g., Certain ointments, creams, lotions, commercial vitamin drops

Question 64

why make an emulsion

what does it mask

are they easier to digest and absorb why or why not

what do they do for drugs that are irritating to what

what does it do for healthy skin?

how fast does it absorb onto skin

Answer 64

To mask the unpleasant taste of many solid powders

The reduced particle size of globules make them more digestible, and more easily absorbed

Drugs that are irritating to the skin are less irritating in the internal phase of an emulsified topical preparation when compared to external phase.

To healthy skin, a w/o emulsion is preferred because it goes on evenly and is softening to the skin

Absorption through the skin is faster with diminished size of internal phase

Question 65

What should a pharmacist consider when selecting an emulsifying agent?

Answer 65

Should not interfere with the action of the other dosage form ingredients

Should be stable and not deteriorate in preparation

Should be non-toxic with respect to intended use and amount consumed by patient

Should possess little odor, taste or color.

Should maintain stability of emulsion for shelf life of product

Question 66

what is an HLB system assigned to

what does it do

Answer 66

assigned to emulsifying agents

rank the level of hydrophilicity or lipophilicity of an emulsifying agent

Question 67

for each activity, what is is assigned HLB

Emulsifiers (w/o)

Emulsifiers (o/w)

Answer 67

Emulsifiers (w/o) 3-6
mostly lipophilic, water is in oil!

Emulsifiers (o/w) 8-18
mostly hydrophilic, oil is in water!

Question 68

what is interfacial tension.

Answer 68

a function of emulsifying agents

When the liquid is in contact with a second liquid in which it is insoluble
(and immiscible), the force causes each liquid to resist breakup into smaller particles. This is called interfacial tension.

Question 69

what is a surfactant (or wetting agent).

Answer 69

A substance that can reduce this tension causing the smaller particles to break up Into smaller drops (or particles) is called a surfactant (or wetting agent). These agents work on the surface of the droplets.

Question 70

what are the 3 theories of how
Emulsification works

Answer 70

Surface tension theory-

Oriented-wedge theory-

Interfacial film theory-

Question 71

what is Surface tension theory-

Answer 71

Reduces the repellent force between the two liquids, diminishing attraction for its own molecules. Do not want them fusing

Question 72

what is Oriented-wedge theory-

where is the perference

how does an O/W or W/O emulsion form

Answer 72

Preference for one phase over another depending on the surfactant agent

an O/W or W/O emulsion forms depending on the character of the emulsifying agent.

Question 73

what is Interfacial film theory-

Answer 73

Each drop of the internal phase of the emulsion is covered by an emulsifying agent, preventing contact of the dispersed phase. The tougher the film the more stable the emulsion.

Question 74

when is an emulsion unstable

Answer 74

The internal phase forms aggregates of globules

Large globules or aggregates of globules rise to the top or fall to bottom of emulsion to form concentrated layers of internal phase—want uniform distribution

If all parts of the liquid of the internal phase separates and forms a distinct layer (on top or bottom of the emulsion)

Microbial contamination and growth and other chemical and physical alterations

Question 75

what is an example of Emulsions

Answer 75

Castor Oil Emulsion:

Question 76

what is Castor Oil Emulsion used for

Answer 76

Used as a laxative for constipation

For radiography and endoscopic examination, working directly on small intestines promoting bowel movements. Too much may cause excessive water loss

Question 77

how much castor oil is used in commercial emulsions

when should you take castor oil emulsions

Answer 77

Amount of castor oil in commercial emulsions varies from 35% to 67%. Amount of oil influences dose required.

Better taken on empty stomach followed by one full glass of water

Question 78

Generally for an emulsion containing 2/3rds oil, what are the doses according to age

Answer 78

Adult dose is 45 ml (three tablespoonsfuls)
Children between 2 and 6 yrs old, 15 ml is sufficient
Children less than 2 years of age, 5 ml is sufficient

Question 79

what are Mineral Oil Emulsion

how do they compare with unemulsified mineral oil?

when are mineral oil emulsions and unemulsified doses taken

Answer 79

An O/W emulsion

Much more palatable than unemulsified mineral oil

Usual dose is 30 mL (unemulsified dose is 15 mL)

Both taken 1 hr before bedtime.

• Want to make sure that water can support it

Question 80

Mineral Oil Emulsion components

Answer 80

Formula: O/W emulsion, lots of water!

Mineral Oil 500 mL
Syrup 100 mL
Vanillin 40 mg
Alcohol 60 mL
Purified water, to make 1000 mL

Question 81

what are gels and magmas

semisolid and semirigid systems

Answer 81

Semisolid particles enclosed by, and interpenetrated by, a liquid.

Semirigid system, where the movement of the dispersing medium is limited by a network of particles of the dispersed phase

Aggregations are controlled
Lattice organization makes them thicker

Question 82

what is needed to form gels

how much gelling agent is used

Answer 82

To form Gels, gelling agents are necessary.

Amount of Gelling agents used is typically <10% (usually in 0.5% to 2.0% range).

Question 83

what are Single phase gels

Answer 83

are homogeneous preparations, there is only one phase, cannot be heterogenous

Question 84

what is the difference between a one and two-phase gel system?

what is magma

Answer 84

If the gel does not appear to have discrete particles, it is called as a one-phase system.

If the gel contains small discrete particles, the gel is called a two-phase system.

a two phase gel system with floccules dispersed in gel

Question 85

how do you make Bentonite Magma, NF

Answer 85

5% bentonite + purified water

Question 86

Patient Counseling PointsFor Suspensions and Emulsions

Describe and demonstrate,

How to shake the emulsion and suspension

How to measure required doses
How to administer a dose

How to recap and store bottles containing product

How to determine if products are physically unstable and thus not recommended for use

Answer 86

Describe and demonstrate,

How to shake the emulsion and suspension

How to measure required doses
How to administer a dose

How to recap and store bottles containing product

How to determine if products are physically unstable and thus not recommended for use

Question 87

what are ointments, creams and gels

Answer 87

“Ointments, creams and gels are semisolid dosage forms intended for topical application”

Question 88

what do unmedicated ointments do

Answer 88

Protectants (covers layer of skin, P), emollients (flexible & pliable, E), lubricants (where there is a lot friction, E)

Question 89

what do Ointments, Creams, and Gels allow for

Answer 89

Local or systemic absorption:
Dermatologic applications treat the skin

Question 90

what are the different application sites of Dermatologic applications Ointments, Creams, and Gels?

Answer 90

Skin, nose, surface of eye, vagina or rectum

Question 91

what are the different types of ointment bases as classified by USP

Answer 91

Oleaginous bases

Absorption bases

Water-removable bases-

Water-soluble bases

Question 92

What is the application site for oleaginous bases

Answer 92

skin

Question 93

what do oleaginous bases provide the skin

what effect does it have

what does it protect from

what is it effective for

what does one application provide

Answer 93

Have an emollient effect, protecting against moisture escape

Effective occlusive dressings

One application for an extended period without drying out

Question 94

do oleaginous bases wash off easily and what are examples of them

Answer 94

Does not wash off easily

Petrolatum, USP

White Petrolatum, USP

Yellow Ointment, USP

White Ointment, USP (see textbook)

Question 95

what is Petrolatum, USP

what is its color

what is it used with

what is it also known as

at what temp does it melt

Answer 95

A purified mixture of semisolid hydrocarbons obtained from petrolatum.

Color ranges from yellowish to amber

Used alone or in combination with other agents as an ointment base

Known as yellow petrolatum and petroleum jelly
- Vaseline (Chesbrough-Ponds).

Question 96

what is White Petrolatum, USP

what is it color

which healthcare provider likes it and why

how is it known commercially?

Answer 96

A decolorized purified mixture of semisolid hydrocarbons from petroleum

Lighter color compared to yellow petrolatum-

Pharmacists prefer this variety in compounding

Commercial product
—White vaseline (Chesebrough-Ponds)

Question 97

when filling white petrolatum, what do you have to be careful with

Answer 97

The product is all the way to the top so the cover is very close

This product implies: it looks like this and is solid from top to bottom, but there could be less in there. But you could have more because we can get rid of air pockets. All depends on the drug product

Question 98

how do you make Yellow Ointment, USP

what is it and where is it from

Answer 98

Yellow wax 50g
Petrolatum 950g

Purified wax derived from honeycomb of bee Apis mellifera.

Question 99

how do you prepare yellow ointment?

what is the viscosity of yellow ointment greater than

Answer 99

Melt yellow wax in a water bath (adding petrolatum until uniform mixture)

Cool and stir

The viscosity of yellow ointment is greater than plain petrolatum- viscosity is the reason why we have variety and why we want it to be apart of the product

Question 100

what are the two types of absorption bases

what do the two types do and what is an example of each

what are absorption bases good for and how is it done

Why are absorption bases not easily washed from the skin’s surface

what are the components of hydrophilic petrolatum, USP

Answer 100

type I

type II

Type I: permit the incorporation of aqueous solutions, producing water-in-oil (w/o) emulsions (e.g., hydrophilic petrolatum*)

Type II: water-in-oil (w/o) that permits additional aqueous solutions (e.g., lanolin).

absorption bases are good for incorporating small amounts of aqueous solutions into hydrocarbon bases.

the aqueous solutions are incorporated into the absorption base, and then incorporating the mixture into the hydrocarbon base.

absorption bases do not wash off well because Because the oil absorbs onto the skin

*Hydrophilic Petrolatum, USP
Cholesterol 30g
Stearyl alcohol 30g
White wax 80g
White petrolatum. 860g

Question 101

what is an example of an absorption base

where Is it from

how is it prepared

how much water do it have

how can more water be added

Answer 101

Lanolin, USP

Obtained from sheep wool

Cleaned, deodorized (otherwise it would smell) and decolorized

No more than 0.25% water– do not need too much water

Additional water may be added by mixing

Question 102

what are Water-Removal Bases

and do they closely resemble

what may it be diluted with

what may it absorb

what is the external phase thus what would you use to dilute with

If external phase is water, would you want to dilute with oil?

what is the internal phase

Answer 102

These are oil-in-water (O/W) emulsions

closely resemble creams

May be diluted with water (aqueous external phase)

May absorb serous discharges

External phase is water

Internal phase is oil

If external phase is water, would you want to dilute with oil? No cause they don’t mix but do with water instead

Question 103

what is an example of a Water-Removable Base

is it oleaginous

how do you make it

Answer 103

Hydrophilic Ointment, USP (NOT OLEAGINOUS)

 Ingredient			Amount (grams) Methylparaben			  0.25 Propylparaben			  0.15 Sodium lauryl sulfate		10.00 Propylene glycol		       120.00 Stearyl alcohol		       250.00 White petrolatum	       250.00 Purified water		       370.00

Question 103

what do Water-Soluble Bases not contain

how do you soften this base

do you need to add more water

large amounts of what is not incorporated into the base

how is it normally used

what is PEG <600

what is >600, <1000

what is PEG 1000

Answer 103

Water-soluble bases do not contain oleaginous components (aka~ greaseless)

Soften with the addition of water, will compromise dosage form, no need to add more water

Large amounts of aqueous solutions are not effectively incorporated in these bases

Normally used for the incorporation of solid substances

PEG <600: Clear, colorless

> 600, <1000: Semisolid

PEG 1000: Wax-like

Question 104

What should a Pharmacist consider for selecting a base

what base should be used

what are cream applied to

what are lotions applied to

what are ointments applied to

Answer 104

Desired release rate of drug from the ointment base?

Desirability of topical or percutaneous drug absorption
Stability of drug in the ointment base

Effect (if any) the drug might have on characteristics of ointment base

Desire for a base to be easily removed with water

Characteristics of the surface to which the base is applied

The base providing the best combination of most desired attributes should be used

Creams, applied to weeping or oozing surfaces

Lotions, usually applied to where friction may occur (under arm pits, thighs)

Ointments, applied to dry and scaly skin surfaces

Question 105

when incorporating a solid into an ointment, what do you do and how long do you mix it

Answer 105

Mix component until uniform mixture:
- use Mortar and pestle
- use Spatula and ointment slab or parchment paper

Question 106

when incorporating a solid into ointments

when do you use stainless steel spatula to incorporate solids into ointments

how do you use the spatula

Answer 106

Use stainless steel spatula except when ingredients react with the stainless steel material (i.e., iodine). A Rubber spatula can replace stainless steel in this case – 2 options:

Thorough rubbing and working of the components together on solid surface until smooth and make preparation uniform.

Question 107

when incorporating a solid into ointments

what is levigation

what kind of levigating agent is used when the

external phase is oil

what if the external phase is water

Answer 107

Levigation is often used to reduce powder particle size to reduce grittiness prior to incorporation of the solid material into the base.

Mineral oil is used for when oil is the external phase

Glycerin is used when water is the external phase.

Question 108

when. incorporating a solid into ointments

How to incorporate liquids into hydrophobic base?

Answer 108

Add solution to minimum amount of hydrophilic base, and then

Add this freshly prepared mixture to the hydrophobic base.

Question 109

small volumes of what can be added to oleaginous bases with ease

Answer 109

alcoholic solutions

Question 110

for prepping ointments
what happens during the fusion method

Answer 110

By this method, “all or some of the components of an ointment are combined by being melted together and cooled with constant stirring until congealed”

Question 111

for prepping ointments

what are the main methods of fusion

Answer 111

Heat-sensitive or volatile components are added when the temperature of mixture is low enough not to cause decomposition or volatilization.

In general, components having the highest melting points are heated to the lowest required temperature to produce a melt. Think of temp.

Question 112

for prepping ointments

what are the two Alternative methods to fusion

Answer 112

Melt the component with the lowest melting point first, followed by the addition of the remaining components in order of their melting points.

2) Melt all components simultaneously, increasing the temperature only as needed

Question 113

Topical applications are not required to be sterile, but antimicrobial action is a must. why

Answer 113

Water content is an issue.

Staphylococcus aureus often found in dermatologic preparations

Question 114

USP states certain products should be tested routinely, these are what kind of products and why

Answer 114

Rectal,

Urethral,

Vaginal

Due to the presence of Yeast and Molds at the site of application

Question 115

how are Topical dermatologic preparations prepared

Answer 115

packaged in either jars, tubes or syringes

Question 116

how are Ophthalmic, nasal, vaginal and rectal preparations-

Answer 116

packaged in tubes or syringes

Question 117

what kinds of packages are used

where must t stored and wiith what onn top

what must be used when necessary

labels for what includes what

Answer 117

Large mouth containers or metal or plastic tubes

Store in cool place in sealed containers

Opaque or light sensitive containers used when necessary

Labels (for ointments, creams) include type of base (water soluble, water insoluble)

Question 118

what are creams

where is it used

Answer 118

“Semisolid preparations containing one or more drug agents dissolved or dispersed in W/O or O/W emulsion or another water-washable base.”

Used topically, rectally and vaginally

Question 119

what is left behind when a cream evaporates

do patents like them and if so why

Answer 119

Generally when creams evaporate a thin residue film consisting of stearic acid (or other oleaginous components) is left behind.

Preferred over ointments by patients and pharmacists since they are easily removed, Still, both options are generally made available.

Question 120

what are gels

what is an example of a gelling agent

where can gels be used

Answer 120

“Semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid, rendered jellylike by the addition of a gelling agent.”

Gelling agent- Carbomers (high MW, water-soluble polymers)

Can be prepared to be used with various routes, including skin, eye, nose, vagina and rectum

Question 121

what determine the viscosity of carbomers

how many carbomers are there and what are they

what are they used for

which has the highest viscosity

Answer 121

The polymeric composition of Carbomers determines their viscosity.

NF contains monographs of 6, they are 910, 934, 934P, 940*, 941 and 1342.

Used as gelling agents at 0.5% to 2.0% in water

• 940 has the highest viscosity
  Gels = Jellies

Question 122

what are pastes

what are they used for

when adding a base what portion is softened

Answer 122

“Semisolid preparations intended for application to skin. They contain more solid material compared to ointments (~25%).This makes them a little stiffer.”

Used to absorb serous secretions, remaining in place after application.

A portion of base is softened prior to incorporating the solids, A portion of the base is used rather than a liquid because the liquid will soften the base.

Question 123

what are plasters

what must be added when putting on

what does it provide for the site

what kinds of variety does it offer

what are examples of plasters

Answer 123

“Solid or semisolid adhesive masses spread on the backing of paper, fabric, moleskin or plastic.”

Adhesive tape- Adhesive plaster are used

Provide prolonged contact at the site.

Unmedicated variety: provide protection or mechanical support at the application site

Medicated variety: Concentration of salicylic acid used in commercial plasters (range from 10-40%) for the treatment of corns of feet.

examples: hansaplast, corn removal plaster

Question 124

what do glycerogelatins contain

to what level is it cooled

what is finne brush used for

how lonng is it applied to the skin for

what is used to treat varicose ulcers

Answer 124

Plastic masses consisting of the following,
gelatin 15%
glycerin 40%
water 35%
medicinal substance 10%
(i.e., zinc oxide)

Melted and cooled to just above body temperature

Fine brush is used to apply the material, and is generally covered with bandage after hardening

Applied to skin for long-term.
Currently, zinc gelatin is used to treat varicose ulcers (aka~ Zing gelatin boot

Question 125

for Ophthalmic Ointments
where is the Major route of drug transport

if the major route is not sufficient, what si the sceodnary route

what are the 3 layers of the cornea

do lipophilic or hydrophilic pass through the 3 layers better

Answer 125

Major route of drug transport in the eye is by simple diffusion via the cornea

If not efficient, secondary routes are conjunctiva and sclera.

Three layered structure of cornea:
-Lipophilic epithelial layer

• Hydrophilic stromal layer
• Less Lipophilic endothelial layer
  on inside (inner layer)

All things considered, lipophilic drugs penetrate these layers better than hydrophilic compounds

Question 126

for ophalmic ointment, what kind of sterilization is required

is dry heat better than the other steriilization

what are the Approved antimicrobial preservatives for othalmic ointments and what concentration,

Answer 126

Special considerations required- steam sterilization is ineffective because cannot penetrate the ointment base.

Dry heat can sterilize but too harsh. So end stage sterilization is not commonly practiced.
- Instead, aseptic techniques are used when each component is added, including weighing of the ingredients.

Methylparaben, (0.05%)
Propylparaben, (0.01%)
Benzalkonium chloride, (0.008%)
All very small

Question 127

for nasal drug delivery, what dosage form is used

what is the nasal passage lined with

what assisted muscus movement

what is the primary treatment approach?

what enables general circulation

what can it deliver?

Answer 127

For nasal delivery ointments and gels are used.

Nasal passage is lined with thin layer of mucus produced by epithelial mucus glands.

Ciliated epithelium assists with mucus movement

Local effects is the primary treatment approach (i.e., nasal decongestants).

The nasal passage’s vascular region enables general circulation, so systemic absorption does occur.

Can be used to deliver insulin, vaccines, polypeptides & proteins.

Question 128

for Dermatologic preparations
what must the drug do

what Factors affect drug penetration ,

what does the skin act as

what makes Dermatologic preparations differenet than TDDS

Answer 128

Drug should both penetrate and be retained in the skin for a specified period

Physicochemical properties of the drug
Characteristics of the vehicle
Concentration of drug in the vehicle
Oil-water partition coefficient (PC)
And general condition of the skin

The skin (like in transdermal delivery systems- TDDS) acts as a natural barrier controlling the rate and extent to which drugs can penetrate it.

However, unlike with TDDS, the therapeutic drug concentration delivered by a dermatologic preparation is not known. So, more qualitative measures are used.

Question 129

for general use of Dermatologic Preparations, what should a patient do

how should the area of application nbe treated

Answer 129

Patient must thoroughly clean the affected area with soap and water

Dry the area with clean soft cloth

Thin layer of medication is applied to skin area, and spread evenly. – Typically 1 to 3 mg of ointment or cream is applied per square centimeter of skin – thin layer

Area of application should remain uncovered unless otherwise stated

Clean hands immediately following use

Question 130

What should a Pharmacist say to a patient?
for the admin

frewuency and use

warning

results

reaction s

D/C

Answer 130

Instruct patient of proper method of administration

Explain frequency and duration of use

Any special warnings,
For e.g., how should it be used during pregnancy?

Therapeutic goals and outcomes

Signs of an adverse response, and what to do if something goes wrong

When should treatment be
discontinued?

Question 131

Patient Counseling PointsFor all Ointments, Creams, Gels

Answer 131

Only a thin film should be applied

Unless otherwise instructed, remove a sufficient quantity from container, apply it, and gently rub into the affected area

Use a protective pad to protect area from being removed from the clothing

Use of lotions and creams should be avoided

Do not rub eyes or touch mouth during handling of application

If patient exhibits sensitivity or intolerance contact pharmacist or physician

Question 132

what is the skin?

how much of it is our body weight

what are the primary functions of the skin

Answer 132

Largest organ, 1.7 m2, 10% body weight.

Primary function (Barrier)
1. UV radiation
2. Chemicals
3. Allergens
4. Microorganisms
5. Loss of moisture, nutrients.

Question 133

what are the 3 main parts of the skin

what is a scopolamine

where can it be placed

what is the thickness behind the ear and what is the penetration rate of steady state

what is the thickness of the thigh and what is the penetration rate of steady state

which one has a faster rate of penetration and why

Answer 133

epidermis

dermis

subcutaneous layer

medication for nausea or motion sickness

can be placed behind the ear or the thigh

thickness behind the ear: 0.084
penetration: 10.0

thickness of thigh: 0.106
penetration: 4.7

behind the ear has a faster rate of penetration because it has a smaller thickness

Question 134

what are the 3 absorption pathways through the SC?

Answer 134

transcellular route

follicular route

intercellular route

Question 135

for Permeation via Appendages
how much skin surface area does it take up

what can it be

what is it used for in TDD

Answer 135

0.1% of the skin surface area.

• May be target site for drug delivery.
• Mostly not significant for transdermal pathway.

Question 136

what is the nature of the intracellular matrix of the trans-cellular toute

what is the phillicity of intercellular lipids?

what does permeation require

Answer 136

• intracellular matrix is relative polar in nature.
• Intercellular lipid are lipophilic.

Permeation requires repeated partitioning (divide into parts) between polar environment and lipophilic domain.

Question 137

what does the intercellular route provide

what is the polar pathway?

what permeates less through the lipid pathways

Answer 137

Provide the only continuous route through the stratum corneum.

• Diffusion of rate limiting region of very polar permeant is the polar pathway.
• Less polar permeant through the lipid pathway

Question 138

describe simple diffusion across SC

what is it driven by

Answer 138

driven by the concentration gradient

the vehicle has to pass through SC, which has to pass through epidermis then dermis

Question 139

what s flux and what is the symbol

what does the symbol equal

what is the partition coefficient of the drug between SC and the vehicle is what

what can flux equal also in terms of dffusion and partition coefficient and what are the symbols

Answer 139

flux (J) - the quantity of material (M) flowing through a cross-section of a barrier (A) in unit time (dt)

J = (dM)/(Adt)

partition coefficient = Ksc

Ksc = Csc/Cv

J = (D(Co - Ci)/h) = (DKscCv)/h

D = diffusion coefficient (area/time)

h = thickness of the barrier (cm)

C = concentration of drugs

Question 140

what is fick’s law

what does input equal

what does output rate equal

what does Cls equal

When input rate = output rate
what is the equation

Answer 140

fick’s law is at steady state,
input rate = output rate

input = dM/dt = A x J

output rate = eliminatiion rate =
Cls x Cpss

Cls = systemic clearance (V/time)
Cpss = Steady state plasma concentration
A * J = Cls * Cpss
Cpss = A * J /Cls

Question 141

Example: Drug Q has a effective plasma concentration of 5 ng/ml. Based on its IV infusion pharmacokinetics study, the systemic clearance of the drug is 10 L/hr. What would be the minimal delivery rate for a transdermal patch for this drug if a effective plasma concentration need to reach?

what is the output and input rate

Answer 141

Output rate = Cls x Cpss = 5 ng/ml x 10 L/hr
=5 μg/L x 10 L/hr = 50 μg/hr

Input rate = A J
For a patch size usually < 50 cm2, target flux should be > 1 μg/cm2/hr.

Question 142

what are the advantages of TDDs

Answer 142

Bypass hepatic “first pass”

• Bypass gastrointestinal
  incompatibility
• Reduce side effects
• Provide predictable and extended duration of activity
• Greater patient compliance
• Reversibility of drug delivery for removal
• Minimize inter- and intrapatient variation

Self administration

• Can use drugs with short half-life
• Administration of drugs with narrow therapeutic window
• Zero order release
• Controlled release for accurate dosing
• Control of plasma levels of potent drugs

Question 143

what are some drugs for half life of TDDs

what is the half life of an important one

how can the activity of the drug be extended

Answer 143

Clonidine
* Fentanyl
* Nicotine
* Nitroglycerin. 2.3 ± 0.6 min
* Scopolamine * Estradiol

The activity of these drugs can be extended through the reservoir of the drugs present in the transdermal delivery devices.

Question 144

disadvantages of TDDs

how does it permeate through the human skin and why

what kinds of drugs are suitable for delivery

how can it affect the skin

are TDDs a good adhesive

Answer 144

Permeation of drugs through human skin is limited
- Stratum corneum is the rate-limiting factor
- Only potent drugs that do not require high plasma levels are suitable for delivery

Skin irritation from adhesives, API, excipients and enhancers
– Contact allergic dermatitis (involves host immunological activity)
– Contact irritant dermatitis (direct toxic injury to cell membranes, cytoplasm or nuclei)

• Poor adhesive of transdermal devices

Question 145

basic components of TDDs

Answer 145

Polymeric matrix or matrices

• Drug (Pharmaceutically Active Ingredient)
• Permeation enhancers and other excipients
• Adhesives

Question 146

what is a polymer matrix

what can it be composed of

Answer 146

it supports matrix structure and regulate the release of the drug from the Patch

Polymer (polypropylene, polyester)

• Cross-linked polymer
• Co-polymer
  Ethylene-vinyl acetate copolymer (EVA) Poly (Vinyl alcohol)-co-(vinyl pyrrolidone)
• Polymer blend (PVA-PVP)

Question 147

Drugs for Transdermal Delivery

how potent must the drug be

what must the half life be

how must K be used

what must the MW be

how must the first pass effect be

how must it affect the skin

what must it be necessayr for

Answer 147

Be potent (10 mg to mg per day)

• Short half-life
• Lipophilicity/Hydrophilicity (predicted by Partition coefficient, K) (logP = 1 - 3.5)
• MW and size of molecules (<500)
• Extent of skin binding
• 1st pass effect is high
• Non-irritating to the skin
• Clinical necessity for steady state delivery

Question 148

what must an enhancers and other excipeitns be

Answer 148

Pharmacologically inert

• Non-toxic, non-irritating, non-allergenic
• Reliable and predictable
• Immediate recovery of the skin
  (reversible disruption of the skin)
• Compatible with the API

Question 149

what are examples of enhancers and other excipients

Answer 149

Lipophilic solvents
- Dimethylsulfoxide (DMSO)
- Dimethylformamide (DMF) 2-Pyrrvolidinone

• Surface active agents
• Sodium lauryl sulfate (SDS)
• Dodecyl methyl sulfoxide
• Two component system
• Propylene glycol-oleic acid
• 1,4 butane diol-linoleic acid

Question 150

how is water an enhancers

what do chemical enhancers do for the drug

what does it do to intercellular lipids

what does it interact with

Answer 150

Hydration causes corneocyte swelling and keratin bundle dissociation

disrupt the highly ordered structure of the intercellular lipids.

• interact with intracellular proteins embedded in the corneocytes to increase the transcellular permeation.

Question 151

what are examples of Pressure sensitive adhesive

what factors must you consider with adhesives
- how must they affect the skin
- skin when dosing?
- how must it be removed
- how must it be inn contact with the skin

Answer 151

Peripheral adhesive
Face adhesive

Factors to consider with adhesives
- Non-irritating/non-toxic
- Adhere to skin aggressively during dosing
- Easily removable
- Excellent contact with skin

Question 152

what are the components of Peripheral Adhesion

Answer 152

backing film

drug reservoir

microporous membrane

adhesive

disc

release liner

Question 153

what are the components of face adhesives

Answer 153

Polyacrylic copolymer

Deponit Glyceryl Trinitrate

Polypropylene

Question 154

what are Pressure-sensitive adhesives

how are they in dry form and at what temperature

Answer 154

“a distinct category of adhesive tapes that in dry form are aggressive and permanently tacky at room temperature.

Question 155

what must the measured surface energy of the adhesive equal

what is the kinetic requirement of adhesion

how must it be removed

what must adhesives not leave behind

what are examples of Adhesives for skin contact

Answer 155

The measured surface energy of the adhesive must be equal to less than that of the human skin.

Kinetic requirement: the material must possess sufficient mobility at room temperature.
Under the condition of application, the adhesive must be able to flow sufficiently.

• Easily removable

Must not leave any residue behind on the skin.

examples:

PIB-based adhesives (polyisobutylene)

• Acylic adhesives (dominates the medical PSA market) A mixture of hard and soft polymers
• Silicone-based PSAs
  long chain polydimethylsiloxane (PDMS) (Tg = -140oC) + benzene- soluble silicate resin.

Question 156

what are some types of TDDs

what are the components of membrane-moderated TDD, what is also another name for it

what are the parts of a monolithic device

what are the parts of adhesives

Answer 156

adhesive device

monolithic device

reservoir device

Membrane-Moderated (Reservoir)
- backing
- drug reservoir
- semipermeable membrane
- adhesive
- protective peel strip

parts of a monolithic device
- backing
- rate-controlling matrix containing drug
- adhesive

parts of adhesive
- backing
- drug - containing adhesive

Question 157

describe skin controlled drug input
- what is the rate for both placements
- what is controlling the rate
- what is an example

describe system controlled drug input
- what is the rate for both placements
- what is controlling the rate
- what is an example

Answer 157

Skin-controlled drug input system
in forearm: rate is 5ug/hr
in the chest: rate is 10ug/hr
- there is no rate-controlling membrane
- example: nitro-disc

system-controlled drug input system
in forearm: rate is 3ug/hr
in the chest: rate is 3ug/hr
- system controls the rate
- example: transderm-scopolamine

Question 158

what is estradiol

what does the oral does undergo

what is the half life

how is it metabolized by the skin

what is it convenient for

what do estrogen increase the risk for

Answer 158

A natural hormone used for the relief of post- menopausal syndromes and osteoporosis.

• Oral dosed undergoes significant 1st pass
• Short half-life = 1 hr
• Not substantially metabolized by skin
• Convenient once to twice a week dosing on the trunk (abdomen, buttock)

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER

Question 159

what does vivelle dot contain

what is it desiigned for

what does it look like

what is it

what kind of liner does it have

Answer 159

Vivelle-Dot® contains estradiol in a multipolymeric adhesive.

The system is designed to release estradiol continuously upon application to intact skin.

1. A translucent polyolefin film
2. An adhesive formulation containing estradiol, acrylic adhesive, silicone adhesive, oleyl alcohol, povidone, and dipropylene glycol
3. A polyester release liner.

Question 160

what kind of drug is Transdermal Scopolamine and where is it found

what is it a cool drug about it

how does it affect the skin

is it potent? and what is the rate

what kind of half-life does it have

what happens when given orally

Answer 160

Antimuscarinic drug, natural ingredient found in belladonna plant used for motion sickness

1st transdermal drug device approved by FDA

Non-irritating

Potent drug: 1 mg/72 hr

Short-half life (2.9 ± 1.2 h)

anticholinergic side- effects when given orally

Question 161

for Scopolamine

describe the Backing layer– what color is it and what does it have

describe the Drug reservoir- what does it have

what is the rate-controlling part

what is the adhesive formulation?

what covers the adhesive layer

Answer 161

(1) Backing layer of tan-colored, aluminized, polyester film

(2) Drug reservoir: light mineral oil, and polyisobutylene

(3) Rate-controlling microporous polypropylene membrane

(4) Adhesive formulation of mineral oil, polyisobutylene, and scopolamine.

(5) A protective peel strip of siliconized polyester, which covers the adhesive layer

Question 162

Clonidine (Catapres-TTS)

what is the primary indication

what does the oral drug undergo

is it water or lipid soluble

does it have a high or low therapeutic concentration

what is the frequency that it is administered

what are its 4 layers

Answer 162

An antihypertensive agent

Oral drug undergoes significant 1st pass

Highly lipid soluble

Low therapeutic concentration (0.2-2 ng/mL)

Once a week

4-layers: backing, reservoir, micro-porous membrane, adhesive formulation

Question 163

Nitroglycerin

what kind of drug is it and what is it for

what is its half life

what is its first pass

what is is the dose

what is the tolerance

what are the side effctes

Answer 163

Antianginal drug used for prevention of angina pectoris due to coronary artery disease

A Vasodilator

Very short-half life (min)

Extensive 1st pass

Low dose (Cpss 1.2 – 10 ng/mL)

Tolerance is common for long term use

Side-effects include headache, dizziness, and hypotension, and skin irritation

Transderm-Nitro (Novartis)
Nitro-Dur (Key)
Deponit (Schwarz Pharma)

Question 164

Nicotine Patches

what does it provide

Answer 164

To provide nicotine replacement therapy to obtain plasma levels of nicotine that would prevent or lessen the severity of the withdrawal symptoms

Question 165

what is Fentanyl (Duragesic®)

what is the amount of fent. released proportional to

what are its 4 parts

Answer 165

DURAGESIC® (fentanyl transdermal system) is a transdermal system providing continuous systemic delivery of fentanyl, a potent opioid analgesic, for 72 hours.

The amount of fentanyl released from each system per hour is proportional to the surface area (25 μg/h per 10 cm2)

1) a backing layer of polyester film

2) a drug reservoir of fentanyl and alcohol USP gelled with hydroxyethyl cellulose

3) an ethylene-vinyl acetate copolymer membrane that controls the rate of fentanyl delivery to the skin surface

4) a fentanyl containing silicone adhesive. Before use, a protectiv

Question 166

for Fentanyl Patches (mylan)

where Is the drug

where is the rate controlled membrane

Answer 166

1. Drug in adhesive Matrix Patch. 2. No rate-controlling membrane.

Question 166

Oxytrol (Oxybutynin) for Overactive Bladder

what is it for

what are the 3 layers

Answer 166

Layer 1 (Backing Film) is a thin flexible polyester/ethylene-vinyl acetate film that provides the matrix system with occlusivity and physical integrity and protects the adhesive/drug layer.

Layer 2 (Adhesive/Drug Layer) is a cast film of acrylic adhesive containing oxybutynin and triacetin.

Layer 3 (Release Liner) is two overlapped siliconized polyester strips that are peeled off and discarded by the patient prior to applying the matrix system.
49

Question 167

what is OXYTROLTM Oxybutynin Transdermal System designed for

what kind of drug is it

Answer 167

OXYTROL is designed to deliver oxybutynin continuously and consistently over a 3- to 4-day interval after application to intact skin

Oxybutynin is an antispasmodic, anticholinergic agent

Question 168

Lidoderm (Endo Pharm)

what are its components

how must lidocaine is in each adhesive patch

what is it the only top. analgesic for

how often is it released

Answer 168

Lidoderm (lidocaine patch 5%) is comprised of an adhesive material containing 5% lidocaine, which is applied to a non-woven polyester felt backing and covered with a polyethylene terephthalate (PET) film release liner. The release liner is removed prior to application to the skin.The size of the patch is 10 cm x 14 cm.

Each adhesive patch contains 700 mg of lidocaine in an aqueous base.

The Lidoderm® patch is the only topical analgesic indicated to treat the pain of postherpetic neuralgia (PHN)

Question 169

Lidoderm for Postherpetic Neurogalia (PHN)

what is PHN

what are shig=gnles cauase by

how long does the cream last

what kind of cream

how many times do you apply it

Answer 169

PHN is the pain after the rash from shingles is gone

 Shingles are caused by chicken- pox infection of nerves

 Pain can last for 6 months

 Zostrix cream

 five-six times a day. It will take two to three weeks of use before the cream will start to work

Question 170

Ortho-Evra (Ortho-McNeil Pharm)

what is it

what hormones does it have

where can it be worn

Answer 170

The ORTHO EVRA birth control patch is a highly effective, weekly hormonal birth control patch that is worn on the skin to prevent pregnancy.

ORTHO EVRA contains two types of hormones: estrogen (ethinyl estradiol) and progestin (norelgestromin).

ORTHO EVRA can be worn in several discreet locations: buttock, abdomen, upper torso, or upper outer arm.

Question 171

what patch is used for Testosterone

Answer 171

androderm

Question 172

what are patient instructions for TDDs

Answer 172

Wash your hands with soap and water before applying the patch. Dry hands completely.

• Clean the area chosen with soap and water. Rinse and wipe the area completely dry with a clean tissue.
• Apply the patch at the same time of day.
• Apply to a non-hairy area of the body.
• Do not apply the patch on skin folds or wear under tight clothing.
• Do not use the same spot all the time but rotate to different areas.
• Do not apply a patch directly after showering, bathing, or swimming.
• Open the package and remove and throw away the protective backing. Do not touch the sticky side.
• Do not cut the patches.
• Attach the patch to the skin and press firmly in place for 10-15 sec. Run your finger along the outside edge of the patch to seal it.
• Remove the throwaway patch after the specified time or before applying the next patch.
• Repeat the above procedure.

Question 173

what are Physical Approaches to Enhance Permeability

Answer 173

Iontophoresis

• Sonophoresis
• Microneedle

Question 174

sonophoresis

what does ultrasonic refer to

what is sonophoresis

what is the power supply attached to

what sends the sound waves through the skin

Answer 174

• Ultrasonic refers to sound waves whose frequency is >20 KHz
• the movement of drugs through living skin and into soft tissue under the influence of an ultrasonic perturbation
• you have a power supply attached to an ultrasonic transducer attached to the skin and the applied formulation sends sound waves through the skin to allow chemicals to pass through the skin

Question 175

ionotophoresis

what are some examples

Answer 175

• a method used to enhance permeability
• mechanisms: electrophoresis, electro-osmosis, increased permeability

how it works:
- put a patch on, this patch is a battery with a + and - end
- an electric current is passed from the positive side to the negative side of the patch battery
- the ionized drug comes from the positive side and follows the current but gets dropped off into the bloodstream.
- the counter ion (which is negative) moves to the negative side

E-Trans Fentanyl Patch (Alza, 2004).
Indication: post operation pain or cancer chronic pain.
Patient self-controllable.

Question 176

microneedles

what is it used for

how can the drug diffuse

where is the drrug absorbed

what are MN made with

what are hollow MN used for

Answer 176

• used for drug deleivery enhancement
  drug can diffuse through residual holes in skin from a topical formulation (solid MN)

drug is absrobed into aqueous layer of the skin (coated MN)

microneedles are made of water soluble or biodegradable materials and released into the skin (dissolving MN)

hollow microneedles are used to inject liquid formulations into the skin (hollow MN)

Question 177

WHAT are capsules

what do you use when a patient cannot swallow

Answer 177

What is a capsule? “ A solid dosage form in which medicinal agents and/or inert substances are enclosed within a small shell of gelatin”

• When a patient is unable to swallow an intact solid dosage form, chewable tablet, instant dissolving tablets, oral liquids, or suppositories are made available

Question 178

hard gelatin capsules

what is it made of

what does it consist of

how is it intended to be used?

what part of hard capsules is soluble in water

what part of hard capsules can be digested and absorbed

what happens when Gelatin is dissolved

how are most gelatins colored?

how is gelatin obtained?

what is the difference between gelatin in air vs when moist?

how much moisture do hard capsules contain?

how is the size of hard capsules determined

sizes of capsules

how many pharmacists compound capsules?

how do pharmacists fill hard capsules?

Answer 178

used to make most capsules

the capsule is made of:
gelatin, sugar & water
they are clear, colorless and tasteless
what it consists of
- has a long base or body with a small diameter
- cap to slide over the base

intended to be
- swallowed whole
- contents should be opened and administered in food or liquid with the acceptance of a pharmacist

the gelatin is soluble in hot water & in warm gastric fluids

gelatin is digested by proteolytic enzymes and absorbed

When gelatin dissolves it exposes its medicinal contents to the gastric (or intestinal) bodily fluids

Most are colored with FD&C and D&C dyes and made opaque by adding titanium dioxide.

Gelatin is obtained by the partial hydrolysis of collagen obtained from
- skin,
- white connective tissue, and
- bones of animals

While stable in air, gelatin is subject to microbial decomposition when moist
Hard capsules: contain between 13-16% moisture, but poor storage conditions can increase this level. Not good!

size is determined by how much material will go inside
sizes: 000 (largest) to 5 (smallest), 8 actual sizes [000,00,0,1,2,3,4 and 5]

A pharmacist may compound capsules of a single medicinal agent, or combination of agents at the precise dosage prescribed for the patient
pharmacists use the punch method to fill capsules:
- Start with the exact number of capsules to be filled
- Powder to be encapsulated and placed on a sheet of paper, clean glass, or porcelain plate
- Using a spatula powder is formed into a cake
- Empty capsule body is held between the thumb and forefinger and “punched” vertically into the powder cake repeatedly until filled

Question 179

soft gelatin capsules

how do they look/are they elegant?

what are they prepared to contain? what kind of liquids cannot be in soft capsules?

when should soft capsules not be used?

what preservatives are used to retard microbial growth

Answer 179

they are pharmaceutically elegant and easily swallowed

Prepared to contain liquid, paste & dry fills
– Liquids that can easily migrate through the capsule shell cannot be encapsulated into soft gelatin capsules– so if the liquid can easily move through the shell, then it cannot be used

When not to be used?:
– When water content is > 5%
– When low molecular weight water-soluble and organic compounds are employed such as
* alcohols, ketones, amines, and esters.

Preservatives such as methylparaben and/or
propylparaben is used to retard microbial growth – these are antifungal

Question 180

capsule size

how is the size determine

what are the size ranges for humans

how many sizes are there for capsules

how can pharmacists utilize the sizes?

Answer 180

the size is always determined by the amount of material to be incorporated

For human use: 000 (the largest) to 5 (the smallest) are commercially available.

There are 8 actual sizes [000,00,0,1,2,3,4 and 5]

• Numerical designations are arbitrary, and do not indicate the capsule’s capacity

A pharmacist may compound capsules of a single medicinal agent, or combination of agents at the precise dosage prescribed for the patient

Question 181

preparation & filling

if things are to be added to preparations to facilitate manufacturing, what must be be

what are the two types of ways to fill capsules?

what must you keep in mind when cleaning and polishing capsules?

Answer 181

they must be:
– Harmless (in the quantities used)
– Do not exceed the minimum amounts required to provide their intended effect
– Do not impair the bioavailability of the product
– Do not interfere with assays to evaluate dosage form

method 1 to fill capsule: torbial torsion scale
- Formulation must be weighed directly to the capsule. It wouldn’t be accurate otherwise.
- To compensate for the weight of the empty capsule being filled, the same capsule must be placed on the other side of the balance with a weight equal to the amount to be filled

method 2: punch method
Pharmacists use the “punch” method
– Start with the exact number of capsules to be
filled
– Powder to be encapsulated and placed on a sheet of paper, clean glass, or porcelain plate
– Using a spatula powder is formed into a cake
An empty capsule body is held between the thumb and forefinger and “punched” vertically into the powder cake repeatedly until filled.

when cleaning and polishing capsules:
- Small amounts of powder may adhere to the outside of capsules after filling

Question 182

cleaning & polishing

what may adhere on the outside of the capsule
what must you do before packaging and dispensing and how do you do it

for large-scale cleaning, what can remove extraneous materials?

Answer 182

Small amounts of powder may adhere to the outside of capsules after filling

Must remove before packaging and dispensing, wipe with clean gauze or cloth
On large-scale cleaning, a vacuum can remove extraneous materials

Question 183

compendial requirements

Things added to preparations to facilitate their manufacture can only be used if?

Answer 183

– Harmless (in the quantities used)

– Do not exceed the minimum amounts required to provide their intended effect

– Do not impair the bioavailability of the product

– Do not interfere with assays to evaluate dosage form

Question 184

inspecting, counting, storage, and handling

are capsules or tablets easier to store and transport

Answer 184

inspecting

counting:

handling:

capsules are Easier storage and transport

Question 185

influences of food on gastric emptying

for light and heavy objects, do they float or sink

Answer 185

the more food in your stomach, the longer it takes for gastric emptying to occur and for the capsule to be absorbed
light objects float on gastric contents

heavy objects fall to the base of greater curvature

Question 186

different types of tablets

are tablets all the same size

why are there smooth tablets
C
M
S
F
G
E
B
I
E
V

Answer 186

Often vary in size,
shape, hardness, thickness, and in their ability to dissolve In fluids.
These tablets are grooved
- Are therefore intended
to be broken into two parts.
- Why? Offers flexibility
Patients can swallow
them easily or use in divided
doses
Compressed tablets (C.T.):
Usually contain the following in addition to medicinal agents
* Diluents or Fillers: Add bulk to prepare a certain size
* Binder or Adhesives: Promote adhesion of the particles
of the formulation
* Disintegrants: Promotes breakup of tablets/drug availability
* Antiadherents/ glidants/ or lubricating agents
* Miscellaneous Adjuncts: Colorants and flavorants to
enhance overall appearance

Multiple compressed tablets (M.C.T.):
More than a single compression
Produces multiple-layered tablet or a tablet within a tablet
Each layer may contain diff. medicinal agents. Why? * Separation may be required to avoid chemical and
physical incompatibility
Staged drug release
General appearance of multiple-layered tablet
Sugar-coated tablets (S.C.T):
Compressed tablet can be covered with a colored or an uncolored sugar layer
– The coating is water soluble
– The coating is quickly dissolved after swallowing
– The coating protects the enclosed drug from the environment
– The coating enhances the general appearance of tablets and permits imprinting of identifying manufacturer’s info.
– Disadvantages to sugarcoating tablets are,
– the time and expertise required in the coating process,
– the increase in size, weight, and shipping costs. * May be 50% larger and heavier than uncoated tablets
Film-coated tablets (F.C.T.):
These compressed tablets are coated with a thin layer of a polymer capable of forming a skin-like film over the tablet
Usually colored
More durable, less bulky, and less time-consuming to apply than sugar-coatings.
Designed to rupture and expose the core tablet at the desired location within the gastrointestinal tract
Gelatin-coated tablets:
GElCAP,
– Capsule-shaped compressed tablets
– Facilitates swallowing and compared to unsealed capsules, gelatin tablets are more tamper-evident
Enteric-coated tablets (E.C.T.):
Have delayed release characteristics
Designed to pass unchanged through stomach intestines where the tablets disintegrate and allow drug dissolution.
Mainly used when by-passing
the stomach to improve drug absorption
Buccal or sublingual tablets:
These are flat, oval tablets intended to be dissolved in the buccal pouch, or beneath the tongue through absorption through the oral mucosa
– An alternative for drugs that are poorly absorbed from the G.I. Tract
– Buccal tablets designed to erode slowly
– Sublingual tablets designed to provide rapid release
Buccal: In direction of the cheek Sublingual: Below or beneath the tongue
The dosage form must remain in place
Total area of absorption is low compared to
other routes- 100 to 170 cm2
– Taste must be bland, or not acceptable for use – must also be a non-irritant
– Drug should not discolor or erode teethLining of the epithelium is keratinized for buccal and
sublingual, but the epithelium for sublingual is thinner.
What does this tell us about drug absorption?
chewable:
Have a creamy base usually of specially flavored and colored mannitol
* Rapid disintegration when chewed or allowed to dissolve in mouth
* Ideally suited for children and adults who have difficulty swallowing solid dosage forms.

molded tablets
ablet triturates (TT) may be prepared by compression and by molding.
* In terms of appearance very soft and soluble
* Diluent: Lactose and Sucrose usually
* Designed for rapid dissolution
* Pharmacists may insert TT inside a capsule or
dissolved in liquids to provide accurate amounts
of potent drugs.

Instant Disintegrating/ Dissolving tablets * Extended Release Tablets (E.R.)

Vaginal Tablets:
Also called vaginal inserts
Uncoated and bullet or ovoid shaped tablets * Inserted in vagina for localized effects
– Antibacterials for the treatment of Vaginitis caused by Hemophilus vaginalis or
– Antifungal for treatment of vulvo vaginitis candidiasis caused by Candida albicans and related species

Question 187

What are suppositories?

do they melt and if so where

what should the shape not cause?

how long should it be retained in the body

what can bases do

which is faster, melting or dissolving

Answer 187

Solid dosage forms used to administer medicinal substances through the rectum, vagina, or urethra

• They melt or dissolve in the body cavity

The shape and size should not cause discomfort

– Should be retained for a required period of time in order to exert a desired effect. Do not want drugs to be released prematurely

bases can either melt or dissolve

melting is faster than dissolving

Question 188

how are Rectal Suppositories inserted

how large are they and what are they shaped as

what determines the suppository weight

how much for adult rectal suppositories weigh

how much do child rectal suppositories weigh

Answer 188

Are inserted with the fingers instead of applicator

• Are usually about 32 mm (1.5 inches), and are shaped like a bullet, a torpedo, or the little finger.
• The density of base and medication in the suppository determines suppository weight

– Adult rectal suppositories weigh about 2 g when cocoa butter (theobroma oil) is employed - larger

– Children rectal suppositories weigh half that of adults and assume a pencil shape - smaller

Question 189

what are vaginal suppositories called

how are they shaped

how much do they weight

what is the base used to prepare

how many active ingredents does it contain

what are some excipients that are used

Answer 189

Vaginal suppositories are called pessaries

• They are globular, oviform, or cone-shaped
• Weigh about 5 g when cocoa butter is the base.

– The base used to prepare an individual manufacturer’s product will determine weight

• May contain one or more active agents that are compatible and do not form eutectic mixtures
• Some excipients used:
• diluents, adsorbents, lubricants, or antimicrobial preservatives (so no need to steam sterilize

Question 190

Urethral Suppositories

what are they called

how are they shaped

what is it intended for

how is it placed and adminstered

what is a muse and what is another name for it

what is the muse suspended in

how much do male urethra suppositories weigh

how much do female urethra suppositories weigh

Answer 190

Urethral suppositories are called bougies,

They are slender or pencil-shaped

• Intended for insertion into the male or female urethra
• This suppository is placed on tip of an applicator and is administered by placing tip into urethra after urination.

– Example: MUSE (alprostadil)- single use application *(see article)

Drug is suspended in PEG 1450 excipient

– Male urethral suppositories:
* 4 grams in weight

– Female urethral suppositories:
* 1/2 that of the male urethral suppository,
* 2 grams in weight.

Question 191

what are rectal suppositories used for

what do anti hemorrhoidal suppositories contain

when inserted what must the suppositories do

Transport from rectal epithelium primarily involves what two transport processes:

which route is the main route

Answer 191

rectal suppositpries are used to relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids

• Antihemmorhoidal suppositories typically contain a multitude of different agents (i.e., local anesthetics, vasoconstrictors soothing emollients, astringents, protective agents etc…)

– When inserted the suppositories must melt or dissolve and distribute drug substances

– Transport from rectal epithelium primarily involves two transport processes:
– Paracellular route (between cells) - main route
– Transcellular route (through cells) or intracellular

Question 192

what does the mucous membrane permit the absorption of

how often s the vagina used for drug delivery

what does the vagina permit

what is the anal canal lined by and what does it cover

how is the suppository inserted

what do the smooth muscles do to the suppository

once the suppository is inserted, what does it do

Answer 192

The mucous membranes of the rectum and vagina permits the absorption of many drug agents.

– The vagina is NOT used as frequently as the rectum for delivering drug substances;

the vagina permits local drug effects only

The anal canal is lined by a mucous membrane that covers the internal sphincter.

Suppository is inserted with the rounded end first so that it can be pushed in with the flat end.

The smooth muscles of the rectum quickly grip the inserted suppository and push it in further.

Once inserted, the cold, solid suppository picks heat from the body and then slowly melts to release the active ingredients inside it.

Question 193

Advantages of suppositories over oral delivery

what drugs are ideal for supp.

how can stomach drugs be given

can the drugs still be destroyed by portal circulation

who is it convenient for

what kinds of patients can it be given to

what kinds of drugs are used in that way

what are some examples

Answer 193

Drugs destroyed or inactivated by the pH, or enzymatic activity of the stomach, are ideal candidates

• Drugs irritating to the stomach may be given without irritation
• Drugs destroyed by the portal circulation may bypass the liver after rectal absorption
• Convenient route for administration of drugs to adult or pediatric patients who prefer not to swallow medication
• Convenient, and effective way to administer drugs to patients experiencing vomiting episodes and used as a tranquilizer
  – Prochloroperazine and chloropromazine

Question 194

Greater absorption expected from a rectum that is without fecal matter than with it. Why?

when can an Evacuant Enema be administered and what does this result in

what can slow down the rate of drug absorption of an enema?

Answer 194

This increases the interaction of drug products with the intended absorbing surface than if fecal matter is there

Evacuant Enema may be administered before the administration of the suppository for better absorption - make sure that the pathway is clear

Diarrhea, circulation route, colonic obstruction due to tumors, and tissue dehydration can all slow down the rate of drug absorption

Question 195

what does the human rectum have

where s there vascularzation

drugs absrobed rectally do what

what do hemorrhoidal veins receieve

what does the lymphatic circulattion assist with

Answer 195

Human rectum:
– Contains 2 to 3 ml of mucous fluid
– No villi or microvilli

Abundant vascularization of the submucosal region of the rectum wall with blood and lymphatic vessels
– Factors include: Colonic content, pH and lack of buffering capacity of rectal fluids

• Drugs absorbed rectally bypass the portal circulation during first pass into the general circulation
• Hemorrhoidal veins surrounding the colon receive the absorbed drug, and initiate its circulation throughout the body bypassing the liver
• Lymphatic circulation assists with rectal drug absorption 13

Question 196

what is the pH of recetal flud and how does this affect the drug

does cocoa butter release fat soluble liquids well, why or why not

what kind of form does the drug have to be in in order for it to be used with cocoa butter base

will a drug that has a high affinity for cocoa butter be released

drug that has lipophilic/hydrophilic form can use what base

Answer 196

Rectal fluids are neutral in pH [no effective buffering capacity] and so drugs will not be changed chemically

While cocoa butter melts rapidly at body temperature it does not mix well in fluids, and so does not release fat soluble drugs very well

Cocoa butter base should therefore be used with ionized (salt form) of drug to maximize bioavailability

drug that has a high affinity for cocoa will not be released because it is very lipophilic

can use cocoa butter base for drug with lipo/hydrophilic base

Question 197

For systemic action using Cocoa butter as base, the ionized (salt) drug form is recommended, rather than un-ionized (base).
* Why?

what can slow down the rate of releaseing un-ionized drugs

what does glycerin and PEG do for drug absorption

Answer 197

Because the ionized drug form will “maximize bioavailability” when cocoa butter is the base

Gelatin and poly-ethylene glycol bases can slow down the rate of releasing un-ionized drugs.

gelatin and polyethylene glycol bases can slow down the rate of releasing un-ionized drugs

Question 198

what are the physicochemical factors of suppositories?

how are they in water?

size

how does it melt in the body

release

Answer 198

Relative solubility in lipid and in water

– Particle size of dispersed drug

– Ability to melt, soften, or dissolve at body temperature

– Ability to release the drug substance

Question 199

for suppository bases

what does it do for local systemic effects?

how should it be at room temp.

Answer 199

Play an essential role in the release of drugs that they hold, and therefore in the availability of the drug for local systemic effects

Should remain solid at room temperature but melt or dissolve at body temperature, to make drug fully available soon after insertion

Question 200

Nature of the base

what must the base be able to do

if the base irritates the mucous membrane, what may happen

When drug retention time in the bowel is limited to 2 hours absorption what

what can alginic acid be used for

what is research used for

Answer 200

Base must be capable of melting, softening or dissolving to release its drug components for absorption

if the base irritates the mucous membrane it might prompt a bowel movement and will prevent complete drug release and absorption but can be prevented with evacuated enema

When drug retention time in the bowel is limited to 2 hours absorption is approximately 40%. Not 100% but for local action is good but not good for systemic action

• Longer-acting drug effects can be achieved with the use of Alginic acid as a component of the suppository base. Can be used as a stable excipient to increase melting temp.
• Research is performed to determine the best formulation for specific purposes

Question 201

what is important to consider for selection of suppository

a lipophilic and hydrophilic drug in a fatty suppository base cannot do what

what kind of base is good for water or oil soluble drugs

Answer 201

Lipid-water partition coefficient of drug is important consideration in selection of suppository base.

A lipophilic drug distributed in a fatty suppository base in low concentrations will not escape to surrounding aqueous fluids as well as a hydrophilic drug.

can combine cocoa

100% cocoa has the most melting if I add PEG, and does not have as much melting

Question 202

what does particle size affect in suppositories

how does particle size affect absorption

Answer 202

For drugs present in suppositories in an undissolved state, the size of the drug particle will influence rate of dissolution and availability for absorption

The smaller the particle size the more readily the dissolution of the particle and the greater the chance for rapid absorption

larger size -> effects rate of dissolution, makes it slower

can control:
particle size using mortar
suppository base
unionized or ionized drug

Question 203

what are the 3 classes of supposiitory base

Answer 203

Fatty or Oleaginous bases

• Water-soluble and water-miscible bases
• Miscellaneous bases

Question 204

fatty or oleaginous base is the Most frequently employed base. Why?

where are fatty or oleaginous base from

what fatty aciids are high in MW

– Various combinations OF FATTY OR OLEAGINOUS BASES are used to,

Answer 204

Because cocoa butter, NF from the roasted seed Theobroma cacao is a member of this class, and was the first base introduced to the market.

Hydrogenated fatty acids of vegetable oils such as palm kernel oil and cotton seed oil.

– Higher MW fatty acids, such as palmitic & stearic acid.

Various combinations are used to,
* Achieve a base with desired hardness for shipment & storage
* Achieve a base with desired quality for optimal absorption.

Question 205

Cocoa butter is good, but

when does cocoa butter melt and what is this good for

what is cocoa butter made of

why does cocoa butter exhibit polymorphism

When cocoa butter is hastily melted at temperatures well above minimum required, and then quickly chilled, it will form a metastable (alpha) crystal form. Not Good! Why bad?

Answer 205

Cocoa butter melts between 30 and 36 °C. This is ideal. It’s a solid at room temperature and melts just below body temperature

– Given that cocoa butter has a high triglyceride (glycerin + fatty acid) content it exhibits polymorphism (several crystal forms).

– When cocoa butter is hastily melted at temperatures well above minimum required, and then quickly chilled, it will form a metastable (alpha) crystal form. Not Good! Why bad?-
———-because Melting point now much lower than cocoa butter, and dosage form may now melt before insertion

needle: form cake, skinny
barrel: better, larger

Question 206

Concerns with use of Cocoa butter

for ths:
When cocoa butter is hastily melted at temperatures well above minimum required, and then quickly chilled, it will form a metastable (alpha) crystal form. Not Good! Why bad?

Melting point now much lower than cocoa butter, and dosage form may now melt before insertion

• how do you fix it

s that good for the patient

how should cocoa butter be melted and what does it ensure

what can lower melting temp. so what should be used instead

Answer 206

You can fix this by allowing the metastable crystal enough time to form a solid. Several days usually required to achieve this.

The problem is that this is useless for the patient, because it takes too much time.

Cocoa butter should be slowly and evenly melted over a water bath of warm water, to avoid unstable crystal formation, and to ensure ß crystals (the good crystal form) upon chilling of the liquid.

Phenol and chloral hydrate can lower melting temperature
* Cetyl ester wax (~20%)
* Beeswax (~4%)
these will not lower temp so use when adding phenol or choral hydrate

Question 207

Water-soluble and water -miscible bases

what s glycern made out of and so when these are used what must be ensured

how fast does glycerin dissolve and in what

how can Urethra suppositories be prepared

what is glycerin made out of

Answer 207

Glycerin (or glycerinated gelatin), is a hydroscopic material (attracts moisture) and so when these suppositories are used they must be protected from moisture to maintain shape and consistency

Glycerin is slow to soften and dissolve in physiologic fluids

Urethra suppositories may be prepared by this base

– Gelatin constitutes about 60% of the weight, glycerin about 20% and aqueous drug portion is 20%

Question 208

what does PEG stand for and what are the melting points at different sizes

PEG suppositories will not melt at what temp.

when will it dissolve and what does ths result in for release rate

what is thi sconventient for

what is PEG made of

what molecular weights does t come in

what color are they

how does hardness ncrease

Answer 208

PEG (Poly-ethylene glycol)

300 (-15 to -18 °C)
1000 (37 to 40 °C)
8000 (60 to 63 °C)
iincrease size comes with increase of temp

PEG suppositories will NOT melt at room temperature,

will dissolve slowly in body fluids. This lowers the release rate of drug substances.

Convenient storage of suppositories too!

PEG (poly-ethylene glycol) are polymers of ethylene oxide and water.

• Come in a number of molecular weights 300 to 8000
• These are clear and colorless liquids
• Hardness of material increases with molecular weight

Question 209

Miscellaneous Bases

what does it consist of

what are hydrophiilic suppository bases used for and what is an example of this

what can be used to prepare suppositoriies

• How and why are emulsifying agents used?

Answer 209

These consist of mixtures of both oleaginous and water-soluble (or water-miscible) material.

• Hydrophilic suppository bases are often used to hold water or aqueous solutions
  – Example: Poly-oxyl 40 stearate (surface-active agent employed suppositories)
• Emulsifying agents (for O/W W/O) can be used to prepare suppositories.

because it has oleaginous and water-soluble material like emulsifying agents,

Question 210

Preparation of suppositories

what is used to prepare it

when is it used?

what is most used today

what will scratches to the molding surface do

what are plastic molds prone to

Answer 210

used for individual and large numbers

– most used today are made from stainless steel, aluminum, brass, or plastic

– scratches to the molding surfaces will make for somewhat rougher surfaces and increase the chances of making imperfect suppositories

– plastic molds are prone to scratching

Question 211

What should a pharmacist communicate to a patient scheduled to take rectal suppositories?

what must happen if it is stored at 4*C

how can you melt the surface of suppositories

what must you do to glycerinated gelatin or PEG suppositories before using

If PEG formulation does not contain at least 20% water, what canbe done

Answer 211

If to be stored at 4 °C suppositories should be warmed to room temperature before insertion

• Rub cocoa butter suppositories gently with fingers to melt the surface to provide lubrication for insertion
• Glycerinated gelatin or PEG suppositories should be moistened (with water) to enhance lubrication
• If PEG formulation does not contain at least 20% water, dipping in water first before insertion will cut down on irritation

run gently under H20, will absorb H20 and help with irritation

if cold, need to warm for insertion to be comfortable

Question 212

how to insert a suppository

Answer 212

1 - remove foil wrapper

2- moisten the supposiitory with water or water based lubricatiing jelly

3- lie on your side and bend yur right knee up toward your chest. Gently push the suppository into your rectum so it is deep enough not to come out

Question 213

• Why use a Vaginal Suppositories?
• for infections
• normal stat e
• birth
• IUDs

what base is commonly used for this

what is usually added to the base

what pH is it buffered to and why

what does acidity do

what is an exmaple of a vaginal suppository

Answer 213

Why Vaginal Suppositories?
– To combat infections in the female genitourinary area
– To restore a normal vaginal mucosal state,
– For contraception.
– Potential for Long term drug absorption with various intrauterine devices (IUDs)

Commonly used base is PEG. Various MWs

• Surfactants and preservatives usually added to base
• Buffered to an acid pH around 4.5 and this resembles the normal vaginal pH

– Acidity discourages pathogenic organisms and provides an environment for colonization of acid-producing bacilli normally present in the vagina

– Ex: Progesterone Vaginal Suppositories
* Micronized progesterone powder is typically used.
* Polyethylene-glycol, cocoa butter bases are used alone or together.

Question 214

Vaginal tablets are more often used than vaginal suppositories. Why?

what is the shape

what is the plastic inserter designed for

what are the tablets deigns to do

Answer 214

Easier to manufacture, more stable, less messy to handle and use

Shape: Ovoid

– Plastic inserter designed for proper placement of the tablet in the vagina usually comes with these tablets.

– Tablets are intended to disintegrate within the vagina where medication is released

Question 215

how are Glycerin based suppositories and glycerinated gelatin suppositories packaged?

how are cocoa butter suppositories wrapped

how are light sensitive materials wrapped individually, what is an example

how should suppositories be store, why

Answer 215

Glycerin based suppositories and glycerinated gelatin suppositories packaged in glass containers and should be closed tightly

Cocoa butter based suppositories are wrapped individually to prevent direct contact

• Light sensitive materials are wrapped in opaque material ex: metallic foil
• Suppositories are adversely affected by heat so store them in a cool place

no warm place

Question 216

Examples of suppositories used today

Answer 216

Bisacodyl 10 mg

Aspirin 300 mg

Hydrocortisone acetate 25 mg

Prochlorperazine 25 mg

Question 217

what are Multiple compressed tablets (M.C.T.):

Answer 217

More than a single compression
Produces multiple-layered tablet or a tablet within a tablet
Each layer may contain diff. medicinal agents. Why? * Separation may be required to avoid chemical and
physical incompatibility
Staged drug release
General appearance of multiple-layered tablet

Question 218

Physiologic factors affecting drug absorption

Answer 218

fecal matter - can decreases the interaction of drug products with the intended absorbing surface, can use an evacuant enema for better absorption

diarrhea, circulation route, colonic obstruction due to tumors, and tissue dehydration - these can slow down the rate of drug absorption

human rectum
- has 2 to 3 ml of mucous fluid
- no villi or microvilli

Abundant vascularization of the submucosal region of the rectum wall with blood and lymphatic vessels
Factors include: Colonic content, pH, and lack of buffering capacity of rectal fluids

portal circulation - Drugs absorbed rectally bypass the portal circulation during the first pass into the general circulation

Hemorrhoidal veins - surround the colon receive the absorbed drug and initiate its circulation throughout the body bypassing the liver

Lymphatic circulation - assists with rectal drug absorption

pH and lack of buffering capacity - drugs will not be changed because rectal fluids are neutral in pH

cocoa butter: While cocoa butter melts rapidly at body temperature it does not mix well in fluids, and so does not release fat-soluble drugs very well
Cocoa butter base should therefore be used with ionized (salt form) drug to maximize bioavailability

use an ionized form of drug when using cocoa butter for systemic issues because it will maximize bioavailability

Question 219

Physicochemical factors of Supp. bases

Answer 219

Relative solubility in lipid and in water

Particle size of dispersed drug

Ability to melt, soften, or dissolve at body temperature

Ability to release the drug substance

Question 220

which of the following is a physiochemical feature influencing drug absorption

the water-lipid partition coefficient of drug

particle size of drug agent

pH of rectal fluids

A & B only

A, B, C

Answer 220

A & B only

Question 221

between 1972 and 2002
on average, how many years did it take to approve a new patch

between 2003-2007, how long does it take to approve a new patch

Answer 221

2.2 years

7.5 months

Question 222

what are the layers of the skin

what is the Stratum Corneum:

Answer 222

stratum corneum

epiderms

dermis

subcutaneous

Stratum Corneum:
“The horny outer layer of epidermis consisting of several layers of flat keratinized,
non-nucleated dead or peeling cells.”

Question 223

The majority of lipid is stored in the extracellular phase in the membrane surrounding cells. why

what does the rate of drug movement depend on

what character should the drug have

Answer 223

Non-polar drugs tend to cross the cell barrier through the lipid-rich regions (transcellular route), whereas the polar drug favor transport between the cells (intercellular route)

Rate of drug movement depends on:
- Concentration in the vehicle
- Aqueous solubility
- Oil-water partition coefficient between stratum corneum and vehicle

• Ideally, the drug should have some aqueous and lipophilic character

Question 224

what do Transdermal Drug Delivery Systems do

Answer 224

Facilitate passage of therapeutic quantities of drug substances through the skin, and into the general circulation for their systemic effect.

Question 225

what chemical enhancers improve percutaneous absorption

what are the general considerations for chemical enhancement

Answer 225

Chemical enhancers improve percutaneous absorption
-Acetone
-Azone
-Poly-ethylene glycol
-DMSO

General considerations:
-Efficacy in enhancing skin permeation
-Low toxicity
-Biocompatibility

Question 226

what are the Indicators of percutaneous drug absorption

Answer 226

Indicators of percutaneous drug absorption
-Measurable blood levels of the drug
-Detectable excretion of the drug
-Clinical response of the patient

Question 227

In the case of scopolamine, the membrane system (not the skin), controls the rate of absorption. Why?

what are the components of scopolamine?

Answer 227

In the case of scopolamine, the membrane system (not the skin), controls the rate of absorption. Why? Rate that drug is released is less than the skin’s ability to absorb

components:
backing
drug reservoir
semipermeable membrane
adhesive
protective peel strip

Question 228

what factors affect percutaneous absorption

Answer 228

Physical and chemical properties of the skin
Molecular weight
Solubility and Pka
Partitioning coefficient
Nature of the carrier vehicle
Condition of the skin

Age
Temperature
Site of administration
Race (Pigmentation -Dark and white skin)
Disease (i.e., Psoriasis)

Question 229

what are the design features for Design feature of transdermal drug delivery systems

Answer 229

Monolithic

Membrane-controlled transdermal systems

Chemical methods

Physical methods

Question 230

what does the monolithic system incorporate and where

what controls the rate of drug release and thus is used in monolithic system

what are the 2 types of monolithic systems

Answer 230

Two types:
(1) With
(2) and without, excess drug inside the matrix

With excess drug: Drug reserve is used to ensure continued drug saturation

Without excess drug: Used to maintain saturation at the stratum corneum layer, only.

Question 231

what are the componenst of monolithic systems

To prepare a monolithic system:
what must be done

what are these system designed to have

Answer 231

film backing

drug/adhesive layer

protective liner

To prepare a monolithic system:
The drug and polymer are both dissolved or blended together, cast as a matrix and dried.

Most of these systems are designed to contain an excess of drug, and thus have drug-releasing capacity beyond the time frame recommended for replacement.

Question 232

what are Membrane-controlled transdermal systems designed to have

what is an example of it

What is the advantage of this system over the Monolithic systems?

Answer 232

Designed to contain a drug reservoir or “pouch”, usually in liquid or gel form, a rate-controlling membrane, and backing, adhesive and protecting layers.

an example: scopolamine

What is the advantage of this system over the Monolithic systems?
As long as the drug in the reservoir system remains saturated, the drug release remains constant

Question 233

how do you prepare Membrane-controlled transdermal systems

what may serve as the control for drug release

Answer 233

To prepare this system the delivery unit is added to the drug reservoir, and sealed by a process called lamination.

Make a note that either the drug delivery system, or the skin, may serve to control drug release.

Question 234

whata re chemical enhancers

how do they work

Examples include

Answer 234

These are chemicals that increase skin permeability by reversibly damaging or by altering the physicochemical nature of the stratum corneum to reduce its diffusional resistance. How?

Increased hydration of the stratum corneum, or

Change properties of lipids and proteins

Examples include: DMSO (dimethylsulfoxide), ethanol, polyethylene glycol etc…

Question 235

what are the Physical methods used to enhance drug delivery and penetration

what is Ionotophoresis

what is Sonophoresis

Answer 235

Iontophoresis
An applied electric field is used to deliver chemicals across the skin membrane by following mechanisms,

Ionic-electric field interaction

Increased permeability

Electroosmosis produces bulk motion of solvent
Ex: Dexamethasone and verapamil

Sonophoresis
High frequency ultrasound used to deliver chemicals across the skin membrane
Chemical enhancers may not be necessary

Ex: hydrocortisone, and salicyclic acid used in gels, creams and in lotions

Question 236

Ionotophoresis: a model
how are drugs delivered

where is current passed through

what can it be used to treat

Answer 236

Charged drug molecules are transported into and through tissues with use of a small direct current

Current is passed through a drug-containing “active” electrode in contact with skin

Can be used to treat areas of inflammation such as tendonitis

Can be used as an alternative to procedures that are more invasive

Question 237

Sonophoresis

Answer 237

The advantage that compounds need not be ionized

More effective than topical applications alone

Cavitation (occurring in keratinocytes) gave rise to better penetration of vitamin A within cells, stimulating mRNA and this produced faster growth of keratinocytes and collagen production.

Question 238

Tranderm-Nitro
(Novartis)

Answer 238

Used to provide controlled release of nitroglycerin.

Used to treat angina.

Where applied?
Chest and upper arm of shoulder areas

Backing:
Aluminized plastic

Drug reservoir content:
Nitroglycerin adsorbed on lactose, colloidal silicon dioxide, and silicone medical fluid

Question 239

Scopolamine

Answer 239

Used to provide controlled release of scopolamine over a 3 day period

Used to treat nausea related to travel particularly by sea

Where applied?
Behind the ear.
One patch removed and another can be applied when desirable

Backing:
Aluminized polyester film

Drug reservoir contents:
Scopolamine, mineral oil, and polyisobutylene

Question 240

Transdermal Nicotine

Answer 240

Dose: 7 to 22 mg of nicotine per/day

Treatment: 6-8 wks
Should be replaced daily
Should be discarded immediately after use
Patients are provided with sustained levels of nicotine in blood

Where applied?
Arm or upper front torso

Question 241

Transdermal Estradiol

Answer 241

Dose: 0.05 or 0.1 mg estradiol per/day

Treatment: 3 weeks of treatment followed by one without and so forth
Patients are provided with 17-β estradiol for conditions associated with menopause, primary ovarian failure etc…
Oral delivery a problem, Why?
Estradiol Estrone

Where applied?
lower stomach area,
below your waistline

Question 242

Fentanyl Patch

Answer 242

Dose: Fentanyl 25 µg/hr
Treatment: 72 hrs

Where applied: Apply the patch to a dry, flat skin area on your upper arm, chest, or back.

This medicine is a tan, square,
transdermal system imprinted
with “FENTANYL 25 mcg/hr”.

Question 243

Advantages of TDDS

Answer 243

Can avoid difficulties with gastrointestinal drug absorption

Can be used as a substitute for oral administration of medication

Can avoid first-pass elimination

The systems are non-invasive

Can provide extended therapy with a single application

Drugs having a short half-life can be extended through the reservoir

Drug therapy may be terminated by removing the application from the skin surface

Ease of rapid identification of the medication in emergency situations

Question 244

Disadvantages of TDDs

Answer 244

Only potent drugs are considered suitable candidates because only low plasma levels of drug can be maintained

Some patients may develop severe response to treatment at the site of application (i.e., dermatitis). In such cases treatments are usually terminated.

Question 245

General considerations in the use of TDDS

Answer 245

Extent of percutaneous absorption may vary according to site of application

TDDSs should be applied to clean dry skin areas

Use of skin lotions should be avoided
TDDS should not be physically altered in any way

Be careful not to damage TDDS when removing from package

Apply to areas not likely to be rubbed off by clothing

Must be worn for the full period of time as discussed in packing insert

Use clean hands when applying and removing TDDS

Always seek medical advice to sensitivity or any intolerance to the TDDS

Remove the patch when finished and discard as recommended.

Keep away from children