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

PHM4153 Dosage Design 2 2011/12

 Examples of Creams
3

• Benzophenone, hydroquinone
Whitening • Fruit extracts

Anti- • Collagen, seaweed extract

ageing • Liposome

• Fish
Virility • Herbs

PHM4153 Dosage Design 2 2011/12

 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

PHM4153 Dosage Design 2 2011/12

 Choice of vehicle
8

Bases from
mixtures of low
Liposomes Microemulsions
and high MW
PEG

Fluorocarbon
Multiple emulsions –
emulsions
ultra low i

PHM4153 Dosage Design 2 2011/12

 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  Odour

 Shine  Colour
 Lubricity  Viscosity
 Miscibility with other
 Spreadability
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 effect
 Inert  Little barrier effect
 Stable against  Varying stability
oxidation 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

 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

PHM4153 Dosage Design 2 2011/12

 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?

PHM4153 Dosage Design 2 2011/12

 20

PHM4153 Dosage Design 2 2011/12

 21

PHM4153 Dosage Design 2 2011/12

 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
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

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

complexation
distribution density surface area

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

PHM4153 Dosage Design 2 2011/12

 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)
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

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

PHM4153 Dosage Design 2 2011/12

 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