pharm. practice exam questions- exam 2 Flashcards
what is a disperse system?
what does a dispersed system have
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
what is a dispersed phase?
what is a continuous phase?
dispersed phase: the distributed substance (the drug)
continuous phase: the vehicle (medium) medium that supports the dispersed phase
what is the range of sizes and categories that a dispersed system comes in
colloidal dimensions: 1.0nm to 0.5 um
fine dispersions: 0.5um to 10um
coarse particles: 10um to 50um
compared to fine dispersions, what do coarse particles do
they have a tendency to separate from the dispersion medium
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
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
why is light agitation of the preparations necessary for dispersed systems
to ensure that the dispersed phase is uniformly spread through the continuous phase. Need to move homogenously regardless if solid or liquid
what is a suspension?
a powdered mixture of drugs with sufficient suspending and dispersing agents to be diluted (and agitated) with a vehicle
how does a pharmacist prepare an antibiotic and why
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
what does reconstitute mean
add solvent or diluent to a medication in powdered form to form a solution
when do you reconstitute
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”
why are pharmaceutical suspensions made?
how is the third option done?
what is erythromycin estolate
- 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.
what are general things to consider for preparing drugs?
- therapeutic efficacy
- chemical stability of the components of the formulation
- esthetic appeal
what are the Specific things to consider for pharmaceutical suspensions keep in mind
- 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
in Specific things to consider for pharmaceutical suspensions, what should we consider for rate of settling
- rate of settling - should be slow and readily dispersed upon gentle shaking, particles redistribute and do not settle too fast
in Specific things to consider for pharmaceutical suspensions, what should we consider for particle size -
particle size - remains constant through long periods of undisturbed standing
in Specific things to consider for pharmaceutical suspensions, what should we consider for the suspension
the suspension should pour evenly from the container, happens if you do not get aggregation
what does the Stokes equation represent
what are the variables and what do they mean
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
what can result in the greatest change in the rate of particles settling in the Influence of dispersion medium on particle settling
Changing the dispersion medium can result in the greatest change in the rate of particle settling.
what can contribute to suspension stability in Influence of dispersion medium on particle settling
Particle size reduction also can contribute significantly to suspension stability.
to increase the rate of settling
would you Increase or Decrease the diameter or size of the particle
increase
larger particles sink faster
to increase the rate of settling
would you Increase or Decrease the the density of the particle
increase
denser/heavier particles sink faster
to increase the rate of settling
would you Increase or Decrease the density of the medium
decrease
particles move slower in denser mediums
to increase the rate of settling
would you Increase or Decrease the viscosity of the medium
decrease
particles move slower in more viscose mediums
what was Stokes’ law derived for
describe this_____
an ideal situation:
particles are
- uniform
- perfectly spherical
- without turbulence
- without physical contact between the particles or particle affinity for the vehicle (medium)
Is Stokes’ ideal situation realistic?
why or why not
what does Stokes’ law allow for
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.
what is generally the size of particles in dispersed phase
1 to 50 μm
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
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
what can affect the stability of a dispersed phase?
what are the two things
The particle shape of the suspensoid can affect the stability
Needle shape versus barrel-shaped particles
what do needle-shaped particles do in the dispersed phase?
: form strong sediment cake on standing that can’t be disturbed upon gentle shaking
what do barrel-shaped particles do in the dispersed phase
do not cake on standing at all
what can you use a floc or floccule for
Consider preventing particle agglomeration into crystals or some larger particulate mass of the dispersed phase by using a floc (or floccule)
what is agglomeration
a mass or collection of things
what do flocculated particles form
what do floc and non-flocculated particles form
what can be said about the agitation of flocculated particles?
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.
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
- 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.
what is a suspensoid
a system consisting of a suspension of solid particles in a liquid.
how much of the suspending agent be used
enough and should not make suspension too viscous
- because these are too difficult to pour.
Whether or not to use a suspending agent depends on what factors,
Density of the suspensoid
Amount of material requiring support
Whether it is flocculated
when preparing suspensions what should pharmacists be aware of
relationship between the dispersed phase and continuous phase
what may the dispersed phase have an affinity for
dispersed medium (vehicle) and is therefore wetted by it.
when does the dispersed phase clump and what is done in this situation?
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
how do hydroscopic agents work
what can also be added to the continuous phase of the suspension?
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.
what are examples of oral suspensions?
Antacid oral suspensions
Antibacterial oral suspensions
Rectal suspensions
Dry powders for suspensions
what are antacid oral suspensions intended for
how are antacds avaible to patients
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
what are most antacid preparations composed on
where does it act
what is the result
water-insoluble material acting within gastrointestinal tract, soothing the irritated or inflamed linings of GI tract.
for antacids what does the Ability to neutralize acid effect depend on
Ability to neutralize acid effects vary according to the chemical reagents employed
what are the 4 problems with antacid oral suspensions
Sodium bicarbonate (SB):
Magnesium preparations (MP):
Calcium carbonate:
Aluminum hydroxide:
for antacids what is the problem with SB and what does it do well
Neutralizes acid effectively.
However, can produce sodium overload and systemic alkalosis.
for antacids what is the problem with MP
Neutralizes acid effectively.
However, can cause diarrhea and cause problems for patients with renal impaired function.
for antacids what is the problem with Calcium carbonate
Neutralizes acid effectively.
However, can also cause hypercalcemia and stimulation of acid secretion (acid rebound).
for antacids what is the problem with Aluminum hydroxide:
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
Why do liquid suspensions provide more immediate action than solids?
absorb faster
how must antacids act
Must be reasonably fast acting since gastric emptying is rapid (~1 hr in fasting stomach following administration).
how long does the FDA. require liquid antacids to disintegrate
within 10 minutes of simulation gastric conditions.
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
Pharmacists must caution patients against taking such drugs concomitantly (together)
so caution against taking calcium-containing drug with antacid
what is barium sulfate, USP
a suspension that can be administered rectally or orally for diagnostic visualization of GI tract. Do not confuse with sulfite
What do antibiotics represent
for oral suspensions, Antibiotics represent the majority of drugs prepared as a dry mix.
what do antibiotic preparations contain
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
when should purified water be used and what does it prevent?
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.
what sized containers should pharmacists use during reconstitution
should the amount of water be estimated
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.
what other official drugs are intended for use as an oral suspension
Cholestyramine (Questran, Par)- for treatment of hyperlipidemia,
Barium Sulfate (Barospere, Mallinckrodt)- for visualization of the gastrointestinal tract, used orally or rectally.
what is an emulsion
“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
what is the external phase of an emulsion
how may an o/w emulsion be diluted
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.
Many _____ preparations that are really _____ are not classified as such, because they fit another _____ more appropriately. For e.g., Certain ____, creams, ____, commercial vitamin drops
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
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
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
What should a pharmacist consider when selecting an emulsifying agent?
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
what is an HLB system assigned to
what does it do
assigned to emulsifying agents
rank the level of hydrophilicity or lipophilicity of an emulsifying agent
for each activity, what is is assigned HLB
Emulsifiers (w/o)
Emulsifiers (o/w)
Emulsifiers (w/o) 3-6
mostly lipophilic, water is in oil!
Emulsifiers (o/w) 8-18
mostly hydrophilic, oil is in water!
what is interfacial tension.
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.
what is a surfactant (or wetting agent).
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.
what are the 3 theories of how
Emulsification works
Surface tension theory-
Oriented-wedge theory-
Interfacial film theory-
what is Surface tension theory-
Reduces the repellent force between the two liquids, diminishing attraction for its own molecules. Do not want them fusing
what is Oriented-wedge theory-
where is the perference
how does an O/W or W/O emulsion form
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.
what is Interfacial film theory-
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.
when is an emulsion unstable
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
what is an example of Emulsions
Castor Oil Emulsion:
what is Castor Oil Emulsion used for
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
how much castor oil is used in commercial emulsions
when should you take castor oil emulsions
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
Generally for an emulsion containing 2/3rds oil, what are the doses according to age
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
what are Mineral Oil Emulsion
how do they compare with unemulsified mineral oil?
when are mineral oil emulsions and unemulsified doses taken
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
Mineral Oil Emulsion components
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
what are gels and magmas
semisolid and semirigid systems
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
what is needed to form gels
how much gelling agent is used
To form Gels, gelling agents are necessary.
Amount of Gelling agents used is typically <10% (usually in 0.5% to 2.0% range).
what are Single phase gels
are homogeneous preparations, there is only one phase, cannot be heterogenous
what is the difference between a one and two-phase gel system?
what is magma
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
how do you make Bentonite Magma, NF
5% bentonite + purified water
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
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
what are ointments, creams and gels
“Ointments, creams and gels are semisolid dosage forms intended for topical application”
what do unmedicated ointments do
Protectants (covers layer of skin, P), emollients (flexible & pliable, E), lubricants (where there is a lot friction, E)
what do Ointments, Creams, and Gels allow for
Local or systemic absorption:
Dermatologic applications treat the skin
what are the different application sites of Dermatologic applications Ointments, Creams, and Gels?
Skin, nose, surface of eye, vagina or rectum
what are the different types of ointment bases as classified by USP
Oleaginous bases
Absorption bases
Water-removable bases-
Water-soluble bases
What is the application site for oleaginous bases
skin
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
Have an emollient effect, protecting against moisture escape
Effective occlusive dressings
One application for an extended period without drying out
do oleaginous bases wash off easily and what are examples of them
Does not wash off easily
Petrolatum, USP
White Petrolatum, USP
Yellow Ointment, USP
White Ointment, USP (see textbook)
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
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).
what is White Petrolatum, USP
what is it color
which healthcare provider likes it and why
how is it known commercially?
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)
when filling white petrolatum, what do you have to be careful with
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
how do you make Yellow Ointment, USP
what is it and where is it from
Yellow wax 50g
Petrolatum 950g
Purified wax derived from honeycomb of bee Apis mellifera.
how do you prepare yellow ointment?
what is the viscosity of yellow ointment greater than
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
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
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
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
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
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
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
what is an example of a Water-Removable Base
is it oleaginous
how do you make it
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
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
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
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
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
when incorporating a solid into an ointment, what do you do and how long do you mix it
Mix component until uniform mixture:
- use Mortar and pestle
- use Spatula and ointment slab or parchment paper
when incorporating a solid into ointments
when do you use stainless steel spatula to incorporate solids into ointments
how do you use the spatula
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.
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
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.
when. incorporating a solid into ointments
How to incorporate liquids into hydrophobic base?
Add solution to minimum amount of hydrophilic base, and then
Add this freshly prepared mixture to the hydrophobic base.
small volumes of what can be added to oleaginous bases with ease
alcoholic solutions
for prepping ointments
what happens during the fusion method
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”
for prepping ointments
what are the main methods of fusion
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.
for prepping ointments
what are the two Alternative methods to fusion
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
Topical applications are not required to be sterile, but antimicrobial action is a must. why
Water content is an issue.
Staphylococcus aureus often found in dermatologic preparations
USP states certain products should be tested routinely, these are what kind of products and why
Rectal,
Urethral,
Vaginal
Due to the presence of Yeast and Molds at the site of application
how are Topical dermatologic preparations prepared
packaged in either jars, tubes or syringes
how are Ophthalmic, nasal, vaginal and rectal preparations-
packaged in tubes or syringes
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
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)
what are creams
where is it used
“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
what is left behind when a cream evaporates
do patents like them and if so why
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.
what are gels
what is an example of a gelling agent
where can gels be used
“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
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
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
what are pastes
what are they used for
when adding a base what portion is softened
“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.
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
“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
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
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
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
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
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,
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
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?
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.
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
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.
for general use of Dermatologic Preparations, what should a patient do
how should the area of application nbe treated
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
What should a Pharmacist say to a patient?
for the admin
frewuency and use
warning
results
reaction s
D/C
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?
Patient Counseling PointsFor all Ointments, Creams, Gels
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
what is the skin?
how much of it is our body weight
what are the primary functions of the skin
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.
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
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
what are the 3 absorption pathways through the SC?
transcellular route
follicular route
intercellular route
for Permeation via Appendages
how much skin surface area does it take up
what can it be
what is it used for in TDD
0.1% of the skin surface area.
- May be target site for drug delivery.
- Mostly not significant for transdermal pathway.
what is the nature of the intracellular matrix of the trans-cellular toute
what is the phillicity of intercellular lipids?
what does permeation require
- intracellular matrix is relative polar in nature.
- Intercellular lipid are lipophilic.
Permeation requires repeated partitioning (divide into parts) between polar environment and lipophilic domain.
what does the intercellular route provide
what is the polar pathway?
what permeates less through the lipid pathways
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
describe simple diffusion across SC
what is it driven by
driven by the concentration gradient
the vehicle has to pass through SC, which has to pass through epidermis then dermis
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
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
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
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
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
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.
what are the advantages of TDDs
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
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
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.
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
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
basic components of TDDs
Polymeric matrix or matrices
- Drug (Pharmaceutically Active Ingredient)
- Permeation enhancers and other excipients
- Adhesives
what is a polymer matrix
what can it be composed of
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)
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
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
what must an enhancers and other excipeitns be
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
what are examples of enhancers and other excipients
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
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
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.
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
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
what are the components of Peripheral Adhesion
backing film
drug reservoir
microporous membrane
adhesive
disc
release liner
what are the components of face adhesives
Polyacrylic copolymer
Deponit Glyceryl Trinitrate
Polypropylene
what are Pressure-sensitive adhesives
how are they in dry form and at what temperature
“a distinct category of adhesive tapes that in dry form are aggressive and permanently tacky at room temperature.
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
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.
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
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
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
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
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
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
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
Vivelle-Dot® contains estradiol in a multipolymeric adhesive.
The system is designed to release estradiol continuously upon application to intact skin.
- A translucent polyolefin film
- An adhesive formulation containing estradiol, acrylic adhesive, silicone adhesive, oleyl alcohol, povidone, and dipropylene glycol
- A polyester release liner.
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
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
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
(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
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
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
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
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)
Nicotine Patches
what does it provide
To provide nicotine replacement therapy to obtain plasma levels of nicotine that would prevent or lessen the severity of the withdrawal symptoms
what is Fentanyl (Duragesic®)
what is the amount of fent. released proportional to
what are its 4 parts
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
for Fentanyl Patches (mylan)
where Is the drug
where is the rate controlled membrane
- Drug in adhesive Matrix Patch. 2. No rate-controlling membrane.
Oxytrol (Oxybutynin) for Overactive Bladder
what is it for
what are the 3 layers
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
what is OXYTROLTM Oxybutynin Transdermal System designed for
what kind of drug is it
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
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
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)
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
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
Ortho-Evra (Ortho-McNeil Pharm)
what is it
what hormones does it have
where can it be worn
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.
what patch is used for Testosterone
androderm
what are patient instructions for TDDs
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.
what are Physical Approaches to Enhance Permeability
Iontophoresis
- Sonophoresis
- Microneedle
sonophoresis
what does ultrasonic refer to
what is sonophoresis
what is the power supply attached to
what sends the sound waves through the skin
- 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
ionotophoresis
what are some examples
- 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.
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
- 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)
WHAT are capsules
what do you use when a patient cannot swallow
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
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?
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
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
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
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?
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
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?
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
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?
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
compendial requirements
Things added to preparations to facilitate their manufacture can only be used if?
– 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
inspecting, counting, storage, and handling
are capsules or tablets easier to store and transport
inspecting
counting:
handling:
capsules are Easier storage and transport
influences of food on gastric emptying
for light and heavy objects, do they float or sink
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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.
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
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
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?
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
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
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
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
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
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
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
what are the physicochemical factors of suppositories?
how are they in water?
size
how does it melt in the body
release
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
for suppository bases
what does it do for local systemic effects?
how should it be at room temp.
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
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
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
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
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
what does particle size affect in suppositories
how does particle size affect absorption
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
what are the 3 classes of supposiitory base
Fatty or Oleaginous bases
- Water-soluble and water-miscible bases
- Miscellaneous bases
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,
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.
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?
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
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
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
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
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%
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
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
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?
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,
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
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
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
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
how to insert a suppository
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
- 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
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.
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
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
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
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
Examples of suppositories used today
Bisacodyl 10 mg
Aspirin 300 mg
Hydrocortisone acetate 25 mg
Prochlorperazine 25 mg
what are 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
Physiologic factors affecting drug absorption
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
Physicochemical factors of Supp. bases
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
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
A & B only
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
2.2 years
7.5 months
what are the layers of the skin
what is the Stratum Corneum:
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.”
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
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
what do Transdermal Drug Delivery Systems do
Facilitate passage of therapeutic quantities of drug substances through the skin, and into the general circulation for their systemic effect.
what chemical enhancers improve percutaneous absorption
what are the general considerations for chemical enhancement
Chemical enhancers improve percutaneous absorption
-Acetone
-Azone
-Poly-ethylene glycol
-DMSO
General considerations:
-Efficacy in enhancing skin permeation
-Low toxicity
-Biocompatibility
what are the Indicators of percutaneous drug absorption
Indicators of percutaneous drug absorption
-Measurable blood levels of the drug
-Detectable excretion of the drug
-Clinical response of the patient
In the case of scopolamine, the membrane system (not the skin), controls the rate of absorption. Why?
what are the components of scopolamine?
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
what factors affect percutaneous absorption
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)
what are the design features for Design feature of transdermal drug delivery systems
Monolithic
Membrane-controlled transdermal systems
Chemical methods
Physical methods
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
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.
what are the componenst of monolithic systems
To prepare a monolithic system:
what must be done
what are these system designed to have
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.
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?
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
how do you prepare Membrane-controlled transdermal systems
what may serve as the control for drug release
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.
whata re chemical enhancers
how do they work
Examples include
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…
what are the Physical methods used to enhance drug delivery and penetration
what is Ionotophoresis
what is Sonophoresis
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
Ionotophoresis: a model
how are drugs delivered
where is current passed through
what can it be used to treat
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
Sonophoresis
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.
Tranderm-Nitro
(Novartis)
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
Scopolamine
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
Transdermal Nicotine
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
Transdermal Estradiol
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
Fentanyl Patch
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”.
Advantages of TDDS
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
Disadvantages of TDDs
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.
General considerations in the use of TDDS
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
