AP - Drug Product Design Considerations Flashcards Preview

CH344 > AP - Drug Product Design Considerations > Flashcards

Flashcards in AP - Drug Product Design Considerations Deck (78):
1

What is a drug substance?

The API e.g. aspirin

2

What is a drug product?

The final formulation that is being administered to the patient. It is the most suitable dosage form for delivering the drug.

3

Name one formulation characterisation test.

- Hardness
- Disintegration profile
- Dissolution
- Friability
- Wettability

4

Name one drug substance characterisation test.

- pKa
- Solubility
- Stability
- Log P

5

What is the most common dosage form for transdermal drug delivery?

Patches

6

Define transdermal drug delivery.

Transdermal drug delivery systems facilitate the passage of therapeutic quantities of the drug substances through the skin and into the general circulation to elicit their systemic effect.

7

In order for transdermal drug delivery to be effective, what is necessary?

Need to have enough concentration to go into the body and through the circulatory system in order to give a therapeutic effect e.g. HRT, contraception

8

Define topic drug delivery

Topical drug delivery systems are designed to deliver the drug INTO the skin for treating dermal disorders, with the skin as the target organ.

9

What is the difference between transdermal and topical drug delivery?

Transdermal goes into systemic circulation. Topical does not go into systemic circulation at all; it only has a local effect.

10

Average area of skin?

1.6 to 1.8m^2

11

How many layers are there in the skin?

Three.

12

What is the outermost layer and what is it's function?

Epidermis.
First barrier - will prevent anything to go into systemic circulation.
Impermeable.
Protective.
Main barrier that decided if the drug even gets in.

13

What is the layer beneath the epidermis?

Dermis.

14

What is the layer beneath the dermis?

Adipose tissue (fat layer)

15

Why do you need to focus on cosmetic appeal?

It is visible, therefore not affect compliance in any way.

16

Advantages of formulation characteristics?

- Ease of manufacture
- Ease of use by patient
- Cosmetically elegant and appealing products

17

Disadvantages of formulation characteristics?

- Dosage control can be difficult (how much is 'finger size') --> this is not enough to cause really bad adverse side effects though

- Not all drugs can be delivered by this route (because absorption is very limited

- Amount of drug available for systemic action is limited due to physicochemical parameters of the drug e.g. Log P (lipophilocity) , pKa (ionisability), solubility

18

What are some pre formulation information you require?

- Identification and chemical info (NMR, mass spec)

- Validated analytical method (HPLC, GLC, UPLC) - to quantify how much of the drug is present in the sample

- Solubility:
a) aqueous - water/ ethanol etc
b) non aqueous - fats/ oils/ liquid paraffin/ waxes

- Stability - is it stable? as a powder? accelerated stability testing. Is it stable in: oxygen, light, heat

- Toxicity

- Physicochemical parameters
a) Melting point (change in chemical structure will show)
b) pKa
c) Log P
d) partical size

19

Name a few topical and transdermal formulations

Ointments
Creams
Pastes
Gels
Lotions
Solutions
Aerosols
Patches
Oils
Lacquers
Powders

20

What excipients are commonly used in a solvent?

Water
Ethanol
Propylene glycol
IPP
IPM

21

What excipients are commonly used in a formulation base (usually gel or matrix)

WSP
Hard paraffin
Carbomer
Cellulose (gel mix)

22

What excipients are commonly used in an antioxidant? (if the drug is susceptible to oxidation in light, oxygen etc)

Vitamin E
Ascorbic acid
Propyl gallate

23

What excipients are commonly used in a metal chelator?

EDTA

24

What excipients are commonly used in preservatives?

Methyl and propyl paraben
benzalkonium chloride

25

What excipients are commonly used for skin penetration enhancers?

Ethanol
Propylene glycol
Glycofurol
Miglyol
IPP
IPM

26

What is the excipient EDTA used for?

Metal chelator

27

What are the excipients water, ethanol, propylene glycol, IPP, IPM used for?

Solvent

28

What is the excipient propyl gallate used for?

Antioxidant

29

What is the excipient carbomer used for?

Formulation base

30

What are the excipients methyl paraben, propyl paraben and benzalkonium chloride used for?

Preservatives

31

What base does an ointment have?

Hydrophobic/ oleaginous base.

32

What application is ointment for?

External application to the skin or mucous membrane.

33

How is the drug in an ointment dissolved?

It is dissolved into the base or in an appropriate solvent and incorporated into the molten base.

34

What does an ointment form on the skin?

It forms a greasy film on the skin.

35

What does the greasy film that is formed by using an ointment do? (3 things)

- Prevents loss of moisture
- Increases skin hydration
- It's occlusive nature allows drug permeation through the skin

36

What conditions are ointments suitable for?

Inflammatory skin conditions such as:
- Psoriasis
- Eczema
- Dermatitis

37

What are the drawback of ointments?

It is very oily and can stick to clothes therefore patient compliance may be affected.

38

What are the excipients used in ointments and what property must they have?

ASHCAWES - need to be non aqueous

Antioxidant
Solvent base
Hydrocarbon base
Chelating agent
Absorption base
Water soluble base
Emulsifying base
Silicone

39

EDTA is an example of?

A chelating agent.

40

Polyethylene glycol (PEG) is an example of?

A water soluble base.

41

Lanolin and Wool alcohol are examples of?

Absorption bases.

42

Isostearyl isostearate and cetomacrogol are examples of?

Emulsifying agents.

43

Propylene glycol, IPP and IPM are examples of?

Solvents.

44

Dimethicone and Cyclomethicone are examples of?

Silicones - for cosmetic use.

45

Give examples of hydrocarbon bases/ fats.

WSP
Hard paraffin
Peanut oil
Coconut oil (Miglyol)
Liquid parrafin
Sesame oil

46

What is the method of preparation for an ointment formulation?

Drug dissolved in solvent.
Heat Liquid paraffin + WSP + Dimethicone.
Add drug solution to molten base and allow to cool with stirring.

47

Define cream.

Semi solid preparations for external application.

48

Advantages of cream over ointment?

Better patient compliance. Very easy to apply. Not as viscous and sticky. Cosmetically appealing.

49

Disadvantages of cream over ointment?

Have to make sure drug stays in solution and does not precipitate out.
Not all drugs are suitable to be delivered as creams.

50

What kind of excipient is propyl gallate?

Anti oxidant.

51

Name two penetration enhancers.

Ethanol and propylene glycol.

52

What is the most important excipient in a cream?

Surfactant. To ensure the formulation remains stable.

53

What is the second most important excipient in a cream (if water based)?

Preservative. Presence of water exposes risk to microbial contamination therefore need methyl or propyl paraben to prevent this from occuring.

54

What are the excipients used in a cream?

Aqueous phase:
Oil Phase: WSP, liquid paraffin, miglyol, vegetable oils

SPACSGP
- Surfactant: Cetomacrogol 1000 (oil soluble), Sorbitan monooleate, Polysorbate 80, Tween 80 (water soluble surfactant)
- Preservative: Methyl paraben, propyl paraben
- Antioxidant: Vit E, BHT, BHA, Propyl gallate
- Chelating agent: EDTA
- Silicone: Dimethicone
- Gelling agent: Carbomer, HEC, HMPC
- Penetration enhancer: Ethanol, Propylene glycol

55

Define gel.

A semi solid system formed by aggregation of colloidal particles interpenetrated by a liquid.

56

What are the two types of gel?

Aqueous
Non aqueous

57

Example of an aqueous gel?

Cellulose, xanthan gum

58

Example of non aqueous gel?

Silicone gels

59

Advantages of gels?

Patient compliance. Very easy and cosmetically appealing.

60

Disadvantages of gels?

Drug must have sufficient solubility. If not, then use a co solvent system OR use complexing agents.

61

Excipients for gels?

APPSGP

(Aqueous gel)
-- Antioxidant: Propyl gallate, Ascorbic acid
- pH regulation: buffer system
- Penetration enhancer: Ethanol, Propylene glycol
- Silicone: Dimethicone, Cyclomethicone, Elastomer
- Gelling agent: carbomer, HEC, HPMC, Xanthan gum, cellulose
- Preservatives: methyl/ propyl paraben, phenoxy ethanol/ benzoic acid

62

Define paste

A semisolid dosage form that is intended for topical application. It generally contains a high concentration of dispersed solids and has a stiff consistency.

63

Creams, pastes and lotions have similar excipients. What is the one excipient that pastes and lotions have that creams do not?

Dispersing agent - Hydrated silica

64

Define lotion

Lotions are aqueous solutions or suspensions from which water evaporates to leave a thin uniform coating go powder on the skin.

65

Main advantage of lotion is that it provides?

soothing effect to skin.

66

Define solution

A liquid preparation with one or more components in a single or multiple miscible solvents for drug delivery.

67

Advantages of solution

- Ease of preparation
- Ease of application
- Aqueous and non-aqueous
- Single or multiple controlled applications

68

Excipients in solution.

CAPP

- Chelating agent: EDTA
- Antioxidant: BHT, BHA, Vit E, Propyl gallate
- Preservative: Methyl and propyl paraben
- Penetration enhancer: Ethanol, Propylene glycol

69

Define aerosol

Pharmaceutical aerosols are pressurised dosage forms that upon actuation emit a fine dispersion of liquid and/or solid materials containing one or more active ingredients in a gaseous medium.

70

Advantages of aerosol

- ease of administration
- quick acting
- covers large surface area

71

There are two types of container and valve assembly. They are:

continuous valve
metered dose valve

72

What are the two types of patches?

Transdermal matrix patch and Transdermal membrane patch

73

Define lacquer

A type of nail varnish. Usually for nail drug delivery.

74

Solvents in lacquer are highly...

volatile.

75

Excipients in lacquer.

SARS
Solvents: Ethanol, Butyl/ Ethyl acetate
Antioxidant: BHT, BHA, Propyl gallate, Vit E
Resins: Eudragit, Gantrez
Surfactants: Glycerol triacetate

76

Typically these are used as a bulking base for powders:

Talc or starch

77

Particle size for powder should be..

Less than 150 um to avoid irritation.

78

Tests performed on topical formulations:

- Rheology
- Homogeneity of drug dispersion in the formulation
- Stability of drug in formulation
- Microscopy and macroscopy to determine any particulates
- pH
- Preservative efficacy testing
- Microbial content
- Particle size
- Drug absorption/ permeation across inert/ skin membranes