Cream Formulation

KAUSAR AHMAD
KULLIYYAH OF PHARMACY

http://staff.iium.edu.my/akausar

PHM4153 Dosage Design 2 2011/12

Contents
2

Ideal Types of
Properties
formulation excipients

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Examples of Creams
3

Benzophenone, hydroquinone
Whitening Fruit extracts

Anti- Collagen, seaweed extract

ageing Liposome

Fish
Virility Herbs

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Formulation
4

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.

PHM4153 Dosage Design 2 2011/12

Ideal formulation
5

Non-irritant Non-allergenic Non-staining

Pleasant
Easy to apply feeling to the Non-toxic
skin

Incapable of
Free from side-
Non-harmful microorganism
effects
growth

PHM4153 Dosage Design 2 2011/12

Formulation requirement: efficacy, safety, and quality
6

Provide drug in a
Convenient to form for
Contain accurate
take or absorption or
dose
administer other delivery to
the target

Manufactured by a
process that does not
Retain quality
compromise
throughout shelf
performance and that is
life & usage period
reproducible and
economical

PHM4153 Dosage Design 2 2011/12

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

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Choice of vehicle
8

Bases from
mixtures of low
and high MW Liposomes Microemulsions
PEG

Fluorocarbon
Multiple emulsions
emulsions ultra low i

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Examples of Oils & Fats
9

Cyclomethicones
Silicones
Dimethicones

Triglycerides/ Castor oil

vege oils Glyceryl tricaprylate

Octyl stearate
Simple esters
Isopropyl palmitate

PHM4153 Dosage Design 2 2011/12

Advantages of Silicones
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

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
Shine
Lubricity
Spreadability Odour
Solvency Colour
Drying
Viscosity
Miscibility with other oils
Toxicity
Impurities
Cost

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 Polarity of oils
13

Non-polar Polar

Lasting emollient effect

Barrier effect
Inert
Stable against oxidation
Varying emollient effect
Shine
Spreadability Little barrier effect
cheap Varying stability against oxidation
Good absorption
Good delivery
expensive

PHM4153 Dosage Design 2 2011/12

Excipients
14

Other components other than API added to formulation

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Categories of excipients
15

Provide essential parts of dosage form & enhance bioavailability

Emulsifiers
Viscosity modifier

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

PHM4153 Dosage Design 2 2011/12

Choosing excipients
16

physiological
inertness

commercially physical and

available at 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
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Penetration enhancers
18

Increase delivery of active substance by:

Disturb packing of SC lipid bilayer

Examples: surfactants

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

Hydration
19

Alter water-binding
Hygroscopic effect capacity of
corneocytes

NaCl Low MW
glycerols
Sorbitol
PPG
glycerol Q. How does urea moisturise the skin?

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 20

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 21

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pH adjustment
22

Triethanolamine

NaoH

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

UV filters
25

Zinc oxide

Titanium dioxide

Benzophenone
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Other types of excipients
26

Soothing
Allantoin

Anti-free radicals
Polyphenols
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Effects of excipients
27

physicochemical
texture and consistency
properties

phase behaviour of
rheological, thermal
the component
and microscopical
emulsifiers.

PHM4153 Dosage Design 2 2011/12

Physicochemical properties
28

Oils susceptible to Aqueous solutions support

oxidation microbial growth

Add antioxidants Add preservatives

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

hydration
solubility hygroscopicity swelling capacity

particle size bulk & tap specific

distribution density surface area complexation

infrared
microbes
spectrum

PHM4153 Dosage Design 2 2011/12

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

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Excipient: Pore volume & pore diameter
32

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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)
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Detection of Incompatibility
34

Cracked Hydrolysis or
cream oxidation

Discoloration Precipitation

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Effect of type of preparation: Absorption of retinyl palmitate
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
Nizoral cream Elomet cream 0.1%
Ketoconazole 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

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References
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

 38

Some materials sourced from the following:

http://www.eastman.com/Markets/Pharmaceutical/Excipients/Excipients_intro.asp
http://www.pharmaceutical-technology.com/contractors/materials/uniqema/
http://www.pformulate.com/
http://images.vertmarkets.com/CRLive/files/Downloads/89FB7970-7376-44A0-B6B6
-4B171E4B978B/InsolubleKollidon.pdf

Thank you to contributors.

PHM4153 Dosage Design 2 2011/12