Vous êtes sur la page 1sur 38
Cream Formulation 1 KAUSAR AHMAD KULLIYYAH OF PHARMACY <a href=http://staff.iium.edu.my/akausar PHM4153 Dosage Design 2 2011/12 " id="pdf-obj-0-3" src="pdf-obj-0-3.jpg">

Cream Formulation

1
1
 

KAUSAR AHMAD KULLIYYAH OF PHARMACY

PHM4153 Dosage Design 2 2011/12

Contents 2 Ideal formulation Types of excipients Properties PHM4153 Dosage Design 2 2011/12
Contents
2
Ideal
formulation
Types of
excipients
Properties
PHM4153 Dosage Design 2 2011/12
Examples of Creams 3 Whitening • Benzophenone, hydroquinone • Fruit extracts Anti- ageing • Collagen, seaweed
Examples of Creams
3
Whitening
• Benzophenone, hydroquinone
• Fruit extracts
Anti-
ageing
• Collagen, seaweed extract
• Liposome
Virility
• Fish
• Herbs
PHM4153 Dosage Design 2 2011/12

Formulation

4
4
Process whereby drugs are combined with other substances (excipients)
Process whereby drugs are combined with
other substances (excipients)

e.g. preservative

to produce dosage forms

 

e.g. cream

suitable for administration to or by patients.
suitable for administration to or by patients.

PHM4153 Dosage Design 2 2011/12

 

Ideal formulation

5
5
Non-irritant
Non-irritant
Non-allergenic
Non-allergenic
Non-staining
Non-staining
Easy to apply
Easy to apply
Pleasant feeling to the skin
Pleasant
feeling to the
skin
Non-toxic
Non-toxic
Non-harmful
Non-harmful
Incapable of microorganism Free from side- effects growth
Incapable of
microorganism
Free from side-
effects
growth

PHM4153 Dosage Design 2 2011/12

Formulation requirement: efficacy, safety, and quality

6
6
 
Contain accurate dose Convenient to take or administer
Contain accurate
dose
Convenient to
take or
administer
Provide drug in a form for absorption or other delivery to the target
Provide drug in a
form for
absorption or
other delivery to
the target
Manufactured by a process that does not Retain quality throughout shelf life & usage period compromise
Manufactured by a
process that does not
Retain quality
throughout shelf
life & usage period
compromise
performance and that is
reproducible and
economical

PHM4153 Dosage Design 2 2011/12

Factors to be considered in formulation 7 Physicochemical properties Choice of vehicle • Waxes and oils
Factors to be considered in formulation
7
Physicochemical properties
Choice of vehicle
• Waxes and oils or emulsions
Categories of excipients
• Provide essential part of the dosage form
• Prevent degradation of the formulation
Stability
PHM4153 Dosage Design 2 2011/12

Choice of vehicle

8
8
 
Bases from mixtures of low and high MW PEG
Bases from
mixtures of low
and high MW
PEG
Liposomes
Liposomes
Microemulsions
Microemulsions
Multiple emulsions
Multiple
emulsions
Fluorocarbon emulsions – ultra low  i
Fluorocarbon
emulsions –
ultra low  i

PHM4153 Dosage Design 2 2011/12

Examples of Oils & Fats

 
9
9
 

Silicones

Cyclomethicones Dimethicones

Triglycerides/ vege oils

Castor oil Glyceryl tricaprylate

Simple esters

Octyl stearate Isopropyl palmitate

PHM4153 Dosage Design 2 2011/12

Advantages of Silicones

10
10
 

Chemical and physical

stable, colourless, odourless

Cosmetic

Skin-feel, gloss/matte

Dermo-toxicology

Not sensitizing, non-comedogenic,

PHM4153 Dosage Design 2 2011/12

 

Examples of Lipids

11
11
 

Hydrocarbons

Mineral oil

Wax

Beeswax

Ether

Dicaprilyl ether

Alcohols

Cetyl alcohol

Acids

Stearic acid

PHM4153 Dosage Design 2 2011/12

Choosing Oils 12 Properties Limitation  Emollient effect  Odour  Colour  Shine  Viscosity
Choosing Oils
12
Properties
Limitation
Emollient effect
Odour
Colour
Shine
Viscosity
Lubricity
Spreadability
Miscibility with other
oils
Solvency
Toxicity
Drying
Impurities
Cost
PHM4153 Dosage Design 2 2011/12
Polarity of oils 13 Non-polar Polar  Lasting emollient effect  Varying emollient  Barrier effect
Polarity of oils
13
Non-polar
Polar
Lasting emollient effect
Varying emollient
Barrier effect
effect
Inert
Little barrier effect
Stable against
oxidation
Varying stability
against oxidation
Shine
Good absorption
Spreadability
Good delivery
cheap
expensive
PHM4153 Dosage Design 2 2011/12
Excipients 14 Other components other than API added to formulation PHM4153 Dosage Design 2 2011/12
Excipients
14
Other components other than API added to formulation
PHM4153 Dosage Design 2 2011/12

Categories of excipients

15
15
Provide essential parts of dosage form & enhance bioavailability
Provide essential parts of dosage form & enhance bioavailability

Emulsifiers Viscosity modifier

Prevent degradation of the formulation: protect, improve safety & enhance stability
Prevent degradation of the formulation: protect, improve safety &
enhance stability

Anti-oxidants Anti-bacterials Preservatives UV absorbers Aid processing during manufacturing

Assist product identification  colour
Assist product identification  colour

PHM4153 Dosage Design 2 2011/12

 

Choosing excipients

16
16
 
 

physiological

inertness

commercially available at

commercially available at physical and chemical

physical and chemical

low cost

stability

absence of

conformance

pathogenic

to regulatory

microbial

agency

organisms

requirements

no interference with drug bioavailability

PHM4153 Dosage Design 2 2011/12

Emulsifiers 17 w/o o/w PHM4153 Dosage Design 2 2011/12
Emulsifiers
17
w/o
o/w
PHM4153 Dosage Design 2 2011/12

Penetration enhancers

18
18
 

Increase delivery of active substance by:

Disturb packing of SC lipid bilayer
Disturb packing of SC lipid bilayer

Examples: surfactants

Disruption of skin barrier
Disruption of skin barrier

Extraction of skin lipids with apolar solvents e.g. acetone Physical stripping Physically or chemically induced irritation

PHM4153 Dosage Design 2 2011/12

19

Hydration

19 Hydration Sorbitol Q. How does urea moisturise the skin? glycerols Low MW corneocytes Alter water-binding

Sorbitol

Q. How does urea moisturise the skin?

glycerols

Low MW

corneocytes

Alter water-binding capacity of

glycerol

PPG

NaCl

Hygroscopic effect

PHM4153 Dosage Design 2 2011/12

20
20

PHM4153 Dosage Design 2 2011/12

21
21

PHM4153 Dosage Design 2 2011/12

 

pH adjustment

22
22
 
 

Triethanolamine

 
 
 

NaoH

 
 

PHM4153 Dosage Design 2 2011/12

 
Preservatives 23 Sodium methyl/butyl/propyl paraben Imidazolidinyl urea PHM4153 Dosage Design 2 2011/12
Preservatives
23
Sodium methyl/butyl/propyl
paraben
Imidazolidinyl urea
PHM4153 Dosage Design 2 2011/12
Anti-oxidant 24 Butyl hydroxy toluene Butyl hydroxy anisole PHM4153 Dosage Design 2 2011/12
Anti-oxidant
24
Butyl hydroxy toluene
Butyl hydroxy anisole
PHM4153 Dosage Design 2 2011/12
UV filters 25 Zinc oxide Titanium dioxide Benzophenone PHM4153 Dosage Design 2 2011/12
UV filters
25
Zinc oxide
Titanium dioxide
Benzophenone
PHM4153 Dosage Design 2 2011/12
Other types of excipients 26 Soothing •Allantoin Anti-free radicals •Polyphenols PHM4153 Dosage Design 2 2011/12
Other types of excipients
26
Soothing
•Allantoin
Anti-free radicals
•Polyphenols
PHM4153 Dosage Design 2 2011/12

Effects of excipients

27
27
 
texture and consistency phase behaviour of the component emulsifiers.
texture and consistency
phase behaviour of
the component
emulsifiers.
physicochemical properties rheological, thermal and microscopical
physicochemical
properties
rheological, thermal
and microscopical

PHM4153 Dosage Design 2 2011/12

Physicochemical properties 28 Oils susceptible to oxidation Aqueous solutions support microbial growth Add preservatives Add antioxidants
Physicochemical properties
28
Oils susceptible to
oxidation
Aqueous solutions support
microbial growth
Add preservatives
Add antioxidants
• E.g. BHT, BHA
• E.g. methyl and
propyl paraben
• BUT these may
affect the
endocrine… ..
PHM4153 Dosage Design 2 2011/12

Physical and chemical properties of excipients

 
29
29
 
solubility hygroscopicity
solubility
hygroscopicity
swelling
swelling
hydration capacity
hydration
capacity
particle size distribution
particle size
distribution

bulk & tap density

specific surface area
specific
surface
area
complexation
complexation

infrared

microbes
microbes

spectrum

 

PHM4153 Dosage Design 2 2011/12

 
Polyamide: Carrier for insoluble ingredients; Protector for sensitive ingredients; Slow delivery & long lasting effect 30
Polyamide: Carrier for insoluble ingredients; Protector for
sensitive ingredients; Slow delivery & long lasting effect
30
7 m, empty spheres
10 m, porous
PHM4153 Dosage Design 2 2011/12
Excipient: Particle size distribution 31 PHM4153 Dosage Design 2 2011/12
Excipient: Particle size distribution
31
PHM4153 Dosage Design 2 2011/12
Excipient: Pore volume & pore diameter 32 PHM4153 Dosage Design 2 2011/12
Excipient: Pore volume & pore diameter
32
PHM4153 Dosage Design 2 2011/12
Incompatibility 33 Chemical Physical Packaging pH/dissociation Immiscibility Formulation and packaging materials pH/disperse Insolubility systems polyvalent cations
Incompatibility
33
Chemical
Physical
Packaging
pH/dissociation
Immiscibility
Formulation and
packaging materials
pH/disperse
Insolubility
systems
polyvalent cations
complexation
cationic and anionic
compounds of high MW
reducing agents (cause
fading of dyes)
PHM4153 Dosage Design 2 2011/12
Detection of Incompatibility 34 Cracked Hydrolysis or cream oxidation Discoloration Precipitation PHM4153 Dosage Design 2 2011/12
Detection of Incompatibility
34
Cracked
Hydrolysis or
cream
oxidation
Discoloration
Precipitation
PHM4153 Dosage Design 2 2011/12

Effect of type of preparation: Absorption of retinyl palmitate

35
35
 

Exercise:

18% absorbed from acetone vehicle

compared to only

4% absorbed from o/w emulsion

Q WHY?

PHM4153 Dosage Design 2 2011/12

Exercise: Determine functions of excipients

 
36
36
 

Nizoral cream

  • Ketoconazole

 

Elomet cream 0.1%

  • Mometasone furoate

   
  • PPG

  • White petrolatum

  • Stearyl alcohol

  • White wax

  • Cetyl alcohol

  • PPG stearate

  • Sorbitan stearate

  • Stearyl alcohol

  • Polysorbate

  • Ceteareth-20

  • Isopropyl myristate

  • Hexylene glycol

  • Sodium sulfite

  • Titanium dioxide

  • Purified water

  • Al starch octenylsuccinate

  • Purified water

  • Phosphoric acid

PHM4153 Dosage Design 2 2011/12

References

37
37
 

Bugay, D. E. (1999). Pharmaceutical excipients : characterization by IR, Raman, and

NMR spectroscopy.

RS201E87B931P

Kibbe, A. H. (2000). Handbook of pharmaceutical excipients.

RS201E87H236K

Rowe, R. C., Sheskey, P. J. & Owen, S. C. (2006). Handbook of pharmaceutical excipients

RS201E87H236K

Rowe, R. C. (2009). Handbook of pharmaceutical excipients.

RS201E87H236K

PHM4153 Dosage Design 2 2011/12