Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacy flashcards > PA20285 MEDICINES DESIGN- formulations of pharmaceutical products > Flashcards

PA20285 MEDICINES DESIGN- formulations of pharmaceutical products Flashcards

0
Q

What are pharmaceutical oral solutions?

A

Oral Solutions are liquid preparations, intended for oral administration, that contain one or more substances with or without flavoring, sweetening, or coloring agents dissolved in water or cosolvent-water mixtures. They are things like cough medicine and gaviscon medicine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What are the advantages of pharmaceutical oral solutions?

A

Easier to swallow (for elderly and infants)
faster therapeutic response than tablets; drug is already dissolved and is ready for absorption.
The BA of oral solutions is better than oral solid doses.
They are homogenous systems with uniform distribution of the drug throughout the preparation-(no issues with phase separation As with emulsions and suspensions as these are SOLUTIONS)
Reduced irritation due to immediate dilution by gastric contents
Tastes of bitter therapeutic agents can be masked by adding sweetners etc (this may be harder to do with tablets)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the disadvantages with oral solutions?

A

Problems involved with manufacture and transport (breakage of bottles)
Grown of a microorganism (bacteria) may occur if it becomes contaminated.
Poor stability of ingredients in a solution. (better stability in solid form).
Solutions have a shorter shelf life than solids forms.
Dose accuracy is harder to get correct eg. Using 5ml spoon may not be done accurately.
Unsuitable for drugs that are chemically unstable in water.
Expensive to ship + bulky to carry.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What factors must be considered when making the solution?

A

Homogeneity of solution; phases mustn’t separate.
Solubility; drug must be soluble to be made into solution.
If solubility is high at the selected pH of formulation, the drug can be readily out into solution.
If solubility is low at selected pH, alternative dosage form should be used as solution not appropriate (eg suspension with surfactants)
If solubility is moderate, use co solvents to enhance solubilty.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a common vehicle to use for oral solutions?

A

Purified water USP

this has low cost & low toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Common co solvents to use when increasing solubilty of a moderately soluble drug?

A

Glycerol (contains 3 OH GROUPS increasing solubility)
Alcohol USP
Propylene glycol USP
POLYETHYLENE GLYCOL (peg)

Can also use SURFACTANTS to increase solubilty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are common excipients of pharmaceutical oral solutions?

A

Buffers (control pH)
Sweetners (nicer taste)
Viscosity enhancing agents (so they’re easier to pour onto measuring spoon)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do antioxidants do?

A

Increase the stability of a drug (if it’s degraded by oxidation)
Antioxidants are oxidised and degraded in preference to the drug therefore they’d protect the drug from degradation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What do preservatives do?

A

Control microorganisms that may get into the solution.
Have anti microbial activity.
Are chemically and physically stable.
Low toxicity
Eg. Benzoin acid and it’s salts, sorbic acid and it’s salts, alkyl esters of PArahydroxybenzoic acid
Remember preservatives don’t make solutions sterile, just reduce microbes. Becomes unsterile as soon as touched and opened

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What needs to be considered for effectiveness of preservatives?

A

Minimum inhibitory concentration(MIC) of preservative
May sure other excipients and pH don’t effect preservative concentration
Need to consider factors that mAy effect preservative efficacy
PH of formulation may have an effect
Presence of micelles/ hydrophillic polymers may reduce the free concentration of preservatives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does the pH of the formulation effect the action of preservatives?

A

Use of acidic preservatives can sometimes be problematic
Acidic preservatives are used however.
Mechanism of action; preservative diffuses into cytoplasm of microorganism and the neutral conditions makes the acidic preservative dissociate making the cytoplasm acidic and stopping further growth of the microorganism.
PH effects the amount of acidic preservative present at a particular pH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do micelles contribute to oral solutions/ what’s there effect on preservatives?

A

They increase the solubilisation of lipophillic drugs.
Usually drug is inside micelle to increase solubility.
Preservatives may have lipophillic properties, therefore they may partition into micelles and decrease the availability of micelles to solubilise the drug, and also decrease the amount of active preservative available to kill microbes.
You can avoid this by increasing the amount of preservative as this will increase the free fraction of active preservative.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do the presence of hydrophilic polymers effect preservatives in oral solutions?

A

The free concentration fraction of preservatives is decreased in the presence of hydrophilic polymers.
This is because preservatives chemically interact with the polymers.
To get around this problem you need to increase the concentration of preservatives in the formulation.
Cat ionic polymers should not be used in conjunction with acidic preservatives!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 4 taste sensations?

A

Bitter , sweet, sour, salty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are flavour adjuncts?

A

Things you add with flavours to the solution to desensitise the taste receptors in the mouth so that bad tasting parts are blocked.
Examples of adjuncts= methanol and chloroform

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why add colourants to solutions?

A

May add to match the flavour eg green with mint flavoured, orange with citrus flavour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What if I have a poorly soluble drug in water?

A

You won’t be able to to use it as an oral solution, only a suspension.
Can’t solubilise a really poorly soluble drug, therefore it’s best to use a different formulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What if my drug in a bottle appears to be cloudy?

A 
Check:
Expiry date
Opened/damaged bottle
Check for contamination
Precipitation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the 3 main types of solutions administered orally?

A

Oral solutions
Oral syrups
Oral exilirs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the usual pH of oral solutions?

A

Ph 7
Unless there’s issues regarding solubility of the drug
Formulated over a broad ph range

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

All components of an oral solution should be soluble! No precipitation

A

.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Tell me some things about oral syrups?

A

Highly concentrated with sugar/ sugar substitute as a flavouring agent
Need to be careful with the choice of vehicle eg. Orange flavoured syrup is acidic which may decrease the solubilty of acidic drugs.
Drugs can be directly incorporated into syrup

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the components of oral syrups?

A

Purified water
Sugar/ sugar substitutes (60-80%) contribute to the viscosity. May use non sucrose bases like sorbitol solution USP.
May want sugar free syrups (for children and diabetic patients) sugar free syrups require inclusion of a viscosity modifying agent.
if there’s a high concentration of sucrose then preservatives arent needed.
Flavours- of natural origin or synthetic flavours (certain flavours may have mild therapeutic activity eg antacids giving a minty taste)
Remember; preservatives aren’t necessarily needed for syrups and exilirs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are oral elixirs?

A

Clear hydro alcoholic solutions
Concentration of alcohol is sufficient to ensure that all the other components remain in solution
Presence of alcohol may be a problem for patients who wish to avoid it
Preservatives are not needed in elixirs with over 12 % alcohol as this is antimicrobial (but preservatives are always required in oral solutions , just not in elixirs or some syrups)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are linctuses?

A

Viscous preparations
Drug is dissolved in a vehicle containing a high % sucrose
Primary for treatment of cough (has soothing actions on mucous membrane)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are mouth washes and gargles for?

A

For treatment of infection and inflammation of the oral cavity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are enemas?

A

For rectal administration
Used for clearance of the bowel
Soften faeces
Osmotic laxatives (increasing water in bowel)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are oral suspensions?

A

Dispersions in which the drug is dispersed in the external phase (vehicle)
Solubility of drug in the vehicle is low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What makes an acceptable suspension?

A

Low rate of sedimentation
The disperse phase is easily redispersed with gentle shaking
Has to have good flow so it can easily be poured
Aesthetically pleasing (look attractive)
Suspensions can be admitstered orally, parenterally, topically

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Problems with oral suspensions?

A

Because the suspension is not homogeneous when not shaken, will we get the correct dose of drug..?
Unstable
Difficult to make them look nice
Bulky to carry

30
Q

Advantages of oral suspensions?

A

Good for low solubilty drugs
Avoid using a large volume of solvent to dissolve drug
Avoids precipitation upon storage when cosolvent used which can happen with oral solutions
Taste masking of drugs
Difficulty of swallowing solid dosage forms

31
Q

What 2 physical properties need to be considered when formulating the pharmaceutical suspension?

A

1) PARTICLE SIZE
Increased stability by modifying rate of particle sedimentation (want to reduce sedimentation)
Particle size should be minimised for better solubilty and dissolution rate.

2) WETTING PROPERTIES of the drug
Insoluble drug particles are hydrophobic therefore they’re not easily wetted (when in body they will become wet) Particles that are poorly wetted can result in aggregation.
Surfactants decrease interfacial tension.

32
Q

What happens with crystallisation in suspensions?

A

Increase storage temperature = smaller particles dissolve in the vehicle leading to crystallisation
Crystals of dissolved drug may form on the surface of larger particles ( increasing diameter of suspended drug particles)
Adding Hydrophilic polymers helps us to decrease crystal growth as these adsorb onto the suspended drug particles protecting them from crystallisation.

33
Q

PHARMACEUTICAL SUSPENSIONS ARE ABSORBED VERY QUICKLY!

A

No disintegrating of tablet is needed

34
Q

What do you need to watch out for with oral suspensions?

A

Stability– sedimentation often occurs which can result in caking of the drug making the suspension unstable, need to think about excipients used
Alternative to suspension = an oral solution with solubilising agent to overcome problem of low solubility of drug
Try to have smallest particles possible
Try to have thicker viscosity to avoid sedimentation and easier to administer on spoon
Try to stop aggregation / flocculation

35
Q

Examples of some hydrophilic polymers used in oral suspensions?

A

Cellulose derivatives eg methyl cellulose
Sodium alginates
Acacia , tragacanth, xanthan gums

36
Q

Vehicles of oral suspensions commonly used ?

A

Purified water USP, buffers

37
Q

What types of excipients are used in suspensions?

A

Same as in solutions
Buffers (control pH)
Sweetners (nicer taste)
Viscosity enhancing agents (so they’re easier to pour onto measuring spoon)

Difference ; excipients are added to physically stabilise the suspension (control rate of sedimentation)
Electrolytes added to control flocculatiom by decreasing zeta potential
Surfactants used
Hydrophilic polymers

38
Q

What are hydrophilic polymers added to oral suspensions?

A

Give physical stability
Adsorb onto surface of suspended drug particles to protect from crystallisation occurring.
One section of polymer adsorbs onto particle and rest of chain into aqueous solution.
If 2 polymer coated particles come towards each other they will repel.
Polymer chains stop the particles coming into close contact as they surround them.
Polymer chains increase viscosity decreasing sedimentation and increasing physical stability of the suspension!!

39
Q

From British pharmacopeia:

A

Suspensions may show a sediment which is readily dispersed upon shaking, to give a suspension that remains sufficiently stable to enable the correct dose to be administered.

40
Q

What may suspensions contain? What type of agents?

A

Suspending agent; helps reduce the sedimentation rate of particles in suspension. These are insoluble particles that are dispersed in a liquid vehicle. The suspending agent works by increasing the viscosity of the liquid vehicle, and thereby slowing down settling in accordance with Stokes Law.

Wetting agent;
A substance that reduces the surface tension of a liquid ( like a surfactant)

Solvents
Tonicity adjusters (to make suspension isotonic with body fluids)
Microbial preservatives
PH adjusters

41
Q

How to manufacture oral suspensions

1) direct incorporation method

A

~if a suspension starts to become flocculated , USE HIGH SPEED MIXING
~ if flocculation is poor, high speed mixing results in increased viscosity, Dilatant flow, and pseudo plastic flow properties.
~ reduce drug particle size by using a ball mill. You can do this during or after manufacture. Alternatively you can use other particle size reduction techniques before incorporating the drug into the vehicle.

42
Q

How to manufacture a suspension

The precipitation method

A

1) drug dissolved in vehicle before precipitation after the addition of a COUNTERION
2) excipients are dissolved in the vehicle. Mix together with drug
3) add diluent to correct the volume (dependent on C required)
Problems : ionic by products may be produced which can cause precipitation if there C is high, precipitated drug washed with aq solvent

43
Q

Oral suspension/ solutions are not sterilised ; only applies to injections.
Bacterial contamination is instead avoided using preservatives .

A

The particle size of dispersed drug in suspensions must be between 0.5- 100 um.
Particles smaller that this are colloidal solutions (micro emulsions)

44
Q

What are the routes of parenteral administration?

A

Intravenous into the large proximal vein. Gives a rapid/ predictable response, can administer large or small volumes here.
Intramuscular into muscle, only small volumes injected here but rapid absorption and response .
Subcutaneous into just underneath the skin. Slower onset of action here. Sometimes decreased absorption of drugs. This is the chosen route for insulin.
Others; intradermal, intrathecal, intrarterial, intracardiac

45
Q

Tell me some advantages of parenteral formulations?

A

Immediate physiological response through I’VE route.
Good route for drugs with poor BA/rapid degradation in GI tract.
Good route for unconscious patients or patients who are vomiting.
Control of dosage and administration can be done by trained staff (insulin by patients).
Can induce local effects not whole body eg. Local anaesthetics.
Can get rapid action and long acting.
Total parenteral nutrition (tube feeding)

46
Q

Definition of parenteral administration?

A

Medicine Taken into the body or administered in a manner other than through the digestive tract, as by intravenous or intramuscular injection

47
Q

Tell me some disadvantages of parenteral administration?

A

Harder to manufacture than others- needs to be sterile(aseptic).
The skill of administration needs to be good, could hurt patient, needs to go in correct place.
Patient could have an allergy to it which would be onset rapidly.
Difficult to control and cut down effects of drugs administered parentally.

48
Q

What do you need to consider when manufacturing parenterals?

A

Solubility, and particle size of drug
Route- I’V shoulD be aqueous solutions, that don’t precipitate in blood, SC AND IM can be suspensions, oil based solutions and aqueous solutions.
The volume administered- only I’VE can handle large volumes. All the rest should be small.
The time for onset of action. Need time for drug to dissolve and absorb with suspensions.

49
Q

When do we use aqueous vehicles in parenteral?

A

Freely soluble or low aq solubilty drugs, in the external phase of emulsions.

50
Q

What do we have to consider with aqueous vehicles for parenteral formulations?

A

Appearance (clear & odourless)
Purity
Sterility; water for injections USP is non sterile, injections have to be sterilised after, or use Sterile water for injections USP.
Water for injections must be free from PYROGENS fever producing compounds
Can remove these by distillation or reverse osmosis, or use bacteriostactic water for injection USP if under 5ml volume.

51
Q

What do you need to consider with non aqueous vehicles in parenterals?

A

Used for aq unstable drugs, water insoluble, suspensions, internal phase of emulsions.
Need to consider;
Use fixed oils
Free from rancidity (chem decompositions)
Pain irritations of injections (due to viscous fixed oils).
Sensitivity to oils.

52
Q

What extras can you add to parenterals?

A

Cosolvents. Potential greater toxicity parenterally. IV toxicity greater than IM / SC. Use glycerol, ethanol.
Surfactants. Same as in solutions and suspensions. Eg’s tween series, polyoxyethylene, polyoxypropylene.
Buffers. Control pH
Polymers for viscosity and drug solubilty. As viscosity increases, it gets more difficult to administer and pain will increase.
Preservatives.
Antioxidants.

53
Q

Need to get osmolarity of parenteral products right! Need to be isotonic with blood serum.
Hypotonic-RBCs will swell and burst.
Hypertonic- water will leave cells and shrink.
However many parenterals for I’V are hypertonic so need to administer slowly.

A

.

54
Q

What types of sterilisation are there for parenterals?

A 
Moist heat sterilisation (steam under pressure)
Dry heat sterilisation (ovens)
Filtration sterilisation
Ionising radiation
Gas sterilisation
55
Q

Aq parenteral solutions preparations :
Dissolve components into mixing vessel
Thermostable drug= moist heat sterilisation. Multidose= add preservative as well.
If not thermostable= sterilise by filtration.

A

Oil based parenteral solutions preparations:
Dry heat sterilisation of oil based part.
Drug incorporated if stable enough after sterilisation.
If not stable; drug firstly dissolved in a sterile oil based vehicle.

56
Q

Does preparation of aqueous parenteral suspensions involve filtration?

A

No

You will filter the drug out!

57
Q

How are oil based parenteral suspensions sterilised?

A

Dry heat sterilisation of oil based vehicle
Sterile drug and sterile vehicle mixed
Filled into final container and sealed

58
Q

What is an emulsion?

A

Disperse system, insoluble liquid is dispersed in a second liquid phase.

59
Q

What makes an acceptable emulsion/cream? (ie. stability, spreadability..)

A

There should be no phase separation due to good physical stability
Flow properties should allow easy removal from container
Easily to spread over effected area
Nice texture (smooth not grainy)
If for oral application (in mouth eg ulcer cream) should be a nice taste.

60
Q

A few advantages of pharmaceutical emulsions?

A

Good for delivering drugs with low aqueous solubility
Can make it taste nice as drug is within the internal phase therefore can flavour/sweeten external phase.
A good way to administer oils with a therapeutic effect as viscosity does not matter.
Reduced irritation after topical administration.
Good if someone can’t swallow oral solid dosage forms

61
Q

Problems with emulsions?

A

THERMODYNAMICALLY UNSTABLE- need correct formulation to ensure no phase separation.
can be difficult to manufacture.

62
Q

3 types of emulsion?

A

Oil in water emulsion
Water in oil emulsion
Multiple emulsion (w/o/w)

63
Q

What determines the type of emulsion?

A

Phase of lower stability will form the external phase (the bulk)
Phase volume of internal phase.
Chemical properties of film surrounding internal phase.
Viscosity of internal and external phases.

64
Q

How to Identify the type of emulsion….

A

Miscibility (mixing) tests:
O/w will mix with water but not oil. W/o will mix with oil not water.
Staining tests with an oil-soluble dye.
Conductivity tests: o/w water is bulk phase it will conduct electricity. W/o, oil won’t conduct the electricity.

65
Q

What contributes to emulsion instability ?

A

Decrease particles size increases viscosity
Wrong emulsifying agents (wrong surfactant choice)
Temperature
Microorganisms

66
Q

What is PHASE INVERSION in emulsions?

A

The switching of an o/w emulsion to a w/o emulsion (or other way round)
This happens when the Critical volume of phase - volume ratio has been reached.
O/w: 74:26. W/o: 40:60

67
Q

In emulsions, hydrophilic polymers adsorb at the interface between disperse phase and external phase.
This enables highly viscoelastic gel like layers to be produced.
Surface active agents : mono moleculare films (not multi)
Hydrophilic polymers contribute to emulsion instability

A

Adsorbed particles also contribute to emulsion instability
The type of emulsion is determined by which phase the drug particles prefer; ie if particles are wetted preferentially by the aqueous phase : o/w emulsion.
Addition of finely divided particles are wetted by both phases (start to gear away from an emulsion).

68
Q

What is the preferred use of o/w emulsions? and w/o?

A

Oral and intravenous admin: o/w (w/o would be too viscous) note emulsions can be administered intravenously!
Topical administration (creams) : o/w and w/o used.
O/w used for water soluble drugs for a local effect. These creams are non-greasy as they’re less viscous.
W/I used for moisturising as they’re viscous.

69
Q

Formulation of emulsions…

A

Think about volume of the internal phase
Droplet size; to reduce it use a colloid mill
Think about viscosity of internal and external phases, creams have increased viscosity .

70
Q

Emulsifying agents…

A

Need to consider the HLB requirements of the internal phase.
Emilsifying agents= surface active agents.
Can calculate % of surfactants required.
Choose whether to have a mixture of surfactants
Determine overall C of surfactant.
Best not to have one surfactant with low HLB and one with high HLB. Add a third surfactant with an intermediate HLB
Surfactants are used to stabilise emulsions and creams , but if you choose the wrong one it can result In Instability.

71
Q

Common surfactants to use in emulsions and creams…

A 
Natural sources:
LANOLIN wax like
LANOLIN ALCOHOLS water absorptive properties
Not natural;
Anionic emulsifying wax
Non ionic emulsifying wax 
Beeswax (increase consistency of creams)
72
Q

What types of excipients are in emulsions and creams??

A

Vehicle of aqueous phase; purified water (sterile water if in injection emulsion)
Buffers may also be present in aqueous phase
Oil phases may consist of vegetable oils, ie cottonseed oil, Arachis oil, almond oil.
Creams have a greater range of excipients eg petrolatum, mineral oil,
Isopropyl myristate to increase permeation through skin, antioxidants, viscosity modifiers,
Both emulsions and creams may contain preservatives.

73
Q

MIXING

A

To dissolve water soluble components of the aq phase and oil soluble components of the oil phase, using turbulent mixing conditions.
For emulsions , on a lab scale use mechanical stirrers
Production scale batches : mechanical stirrers, homogenisers, ultrasonifiers.
Creams: to mix the 2 phases use a mortar and pestel

Pharmacy flashcards (52 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions