This document discusses quality control tests for topical preparations, including transdermal drug delivery systems (TDDS). It describes various types of topical preparations like creams, ointments, gels, pastes, and jellies. It also discusses the common ingredients in TDDS like drugs, liners, adhesives, permeation enhancers, backing layers, and polymer matrices. Finally, it outlines the key physicochemical tests performed for quality control of TDDS, including thickness, weight uniformity, drug content, content uniformity, moisture content, and moisture uptake testing.

1. Quality control tests for
topical preparations
Under the guidance of- Presented by-
Mrs Indira Priyadarshini, M.pharm, Bhavana.G.(Y15MPh223)
Assistant Professor, I/II M.pharm
Dept. Pharm. Analysis

2.  Drug products topically administered via the skin fall into two general
categories, those applied for local action and those for systemic effects
after absorption through the skin into the blood circulation.
 Local actions include those at or
on the surface of the skin, Common
products in the former category
include creams, gels, ointments,
pastes, suspensions, lotions, foams, sprays, aerosols, and solutions.
 Creams, ointments, and gels generally are referred to as semisolid
dosage forms.

3.  The most common drug products applied to the skin for systemic effects are
referred to as self adhering transdermal drug delivery systems (TDS) or
transdermal patches.
Functions of Dermatologicals
• Protect injured areas from the environment
• Provide skin hydration (emollient)
• Vehicle for medication transport

5. Physical properties
a) Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non
staining
f) Non hygroscopic
Physiological
properties
a) Non irritating
b) Do not alter
membrane function
c) Miscible with skin
secretion

7. • Ointments are homogenous, translucent, viscous, semi solid preparation
intended for external application to skin or mucous membranes. Ointment
may be medicated or not..
Applied to mucous membrane or skin
Uses
• Emollient
• Application for active ingredients to the skin
• Occlusive

8. • They should be:
 Compatible with skin ph. and drug
 Inert ,non irritating and non sensitizing
 Good solvent and/or emulsifying agent
 Emollient , protective , non greasy and easily removable
 Release medicaments easily at the site of administration
 Pharmaceutical elegant and possess good stability.

9. OINTMENT
BASES
OLEAGINOUS
BASES
Examples:
Hydrocarbons
Animal
fats/vegetabl
e oils
White
petrolatum
White
ointment
WATER SOLUBLE
BASES
Examples:
Polyethylene
Glycol
Ointment,
Biozyme
Ointment,
Desenex
Ointment.
ABSORBTION
BASES
EMULSION
BASES
Examples:
Hydrophilic
petrolatum
Aquaphor
Aquabase
OINTMENTS
WATER
IN OIL
OIL IN
WATER

10. Oleaginous
Bases
Absorption
Bases
Water/Oil
Emulsion
Bases
Oil/Water
Emulsion
Bases
Water-
miscible
Bases
Composition oleaginous compounds
(water insoluble
hydrophobic oils and
fats)
oleaginous base +
w/o surfactant
oleaginous base +
water (< 45% w/w)
+ w/o surfactant
(HLB <8)
oleaginous base +
water (> 45% w/w)
+ o/w surfactant
(HLB >9)
Polyethylene
Glycols (PEGs)
Wash ability Non-washable Non-washable non- or poorly
washable
washable washable
Stability oils poor;
hydrocarbons better
oils poor;
hydrocarbons
better
unstable,
especially alkali
soaps and natural
colloids
unstable,
especially alkali
soaps.
stable
Uses Protectants,
émollients.
protectants,
emollients,
vehicles for
aqueous solutions.
emollients,
cleansing creams,
vehicles for solid,
liquid, or non-
hydrolysable drugs
emollients,
vehicles for solid,
liquid, or non-
hydrolysable drugs
drug vehicles
Examples White Petrolatum,
White Ointment
Hydrophilic
Petrolatum,
Anhydrous Lanolin
Cold Cream type,
Hydrous Lanolin,
Rose Water
Ointment
Hydrophilic
Ointment.
PEG Ointment,
Poly-base.

11. Ointment Preparation
• Incorporation: components are mixed until a uniform preparation is
attained.
• Mortar/Pestle, Ointment Mill
• Fusion: All components are combined by being melted together and cooled
with constant stirring until congealed.
-- High melting temperature bases such as beeswax, paraffin, stearyl alcohol.
Preservatives
• Some bases , although, resist microbial attack but because of their high water
content, it require an anti microbial preservative.
 Commonly used preservative include:
Methyl hydroxy benzoate, Propyl hydroxy benzoate, Chlorocresol

12. Viscous semisolid preparations meant for external use. They contain water
soluble base which are easily removed from the skin.
TYPES
Aqueous creams
Oily creams

13. Aqueous creams: These are O/W type. These are again divided into 3 types based
on emulsifying agent.
(a) Anionicemulsifying wax creams: These are prepared by fusion method. The
wax and oily ingredients are melted and cooled at 60°C.
(b) Cationicemulsifying wax creams: These are made as that of Anionic
emulsifying wax creams. Ex: Cetrimide, Cetostearyl alcohol.
(c) Non ionic emulsifying wax creams: Similar to above. Ex: Polysorbates,
Sorbitan esters.
Oily creams:These are W/O type. These are again divided into 2 types based on
emulsifying agent.
(a) Sterol creams: Here wool-fat is used as emulsifying agent.
(b) Soapcreams: Tri-ethanolamine soap, calcium soap are used as emulsifying
agents.

14. • These are semisolid preparations intended for external application to the
skin. These don’t melt at ordinary temperature and form a protective
coating over the area they are applied.
USES:
1. Antiseptic
2. Protective
BASES USED FOR PASTES
HYDROCARBON BASES Ex: Liquid paraffin, Soft paraffin.
WATER MISIBLE BASES Ex: Glycerine.
WATER SOLUBLE BASES Ex: Polyethylene glycols.

16. These are transparent, translucent non-greasy semi solid preparations meant
for external application to the skin or mucous membrane.
EX: Tragacanth, Pectin, Sodium alginates etc..
Types of jellies
MEDICATED JELLIES
LUBRICATING JELLIES
MISCELLANEOUS JELLIES
Formulations of jellies
Gelling agents: usually organic hydrocollides. Example : tragacanth, sodium
alginate, pectin, gelatin, cellulose derivatives

17. TRANSDERMAL PREPARATIONS
• Designed to support the passage of drug substances from the
surface of the skin, through its various layers, and even into the
systemic circulation.
Advantage of TDDS over other delivery systems : is that the patch
provides a controlled release of the medication into the patient, usually
through either a porous membrane covering a reservoir of medication or
through body heat melting thin layers of medication embedded in the
adhesive.
Disadvantage: is that skin has very effective barrier so small molecules which
can easily penetrate are used.

18. • ADVANTAGES
 Self administration is possible with these system.
 The drug input can be terminated at any point of time by removing
transdermal patch.
Allows effective use of drugs with short biological half-life
Allow administration of drugs with narrow therapeutic window
Provides controlled plasma level of very potent drugs
Drug input can be promptly interrupted when toxicity occurs
• DISADVANTAGES:
Drug or drug formulation may cause skin irritation or sensitization.
Uncomfortable to wear . May not be economical.

19. mechanism

20. The common ingredients which are used for the preparation of TDDS are as
follows.
1. Drug: Drug is in direct contact with release liner. Ex: Nicotine,
Methotrexate.
2. Liners: Protects the patch during storage. Ex: polyester film.
3. Adhesive: Serves to adhere the patch to the skin for systemic delivery of
drug. Ex: Acrylates, Poly-iso-butylene, Silicones.
4. Permeationenhancers: Controls the Release of the drug. Ex: Terpenes,
Terpenoids. Solvents like alcohol, Ethanol, Methanol etc.
5. Backing layer: Protect patch from outer environment. Ex: Cellulose
derivatives, poly vinyl alcohol, Polypropylene Silicon rubber.
6. Polymer matrix: The polymer controls the release of the drug from the
device. Ex: Natural polymers, Synthetic Elastomers, Synthetic Polymers

21. • Idealpropertiesof polymersforTransdermaldrugdeliverysystem.
 The polymer should be stable.
 non-reactive with the drug.
 easily manufactured and fabricated into the desired product and
inexpensive.
 The polymer and its degradation products must be non-toxic or non-
antagonistic to the host.
 The mechanical properties of the polymer should not deteriorate excessively
when large amounts of active agent are incorporated into it.

22. TYPES OF TRANSDERMAL PATCHES
SINGLE LAYER DRUG ADHESIVE MULTI LAYER DRUG ADHESIVE
MATRIX RESERVOIR PATCH

23. Quality control tests for topical
preparations(TDDS)
 Physicochemical evaluation
 In vitro evaluation
 In vivo evaluation
1. Physicochemical Evaluation
Thickness: The thickness of transdermal film is determined by travelling
microscope, dial gauge, screw gauge or micrometre at different points of the
film.
Uniformity of weight: Weight variation is studied by individually
weighing 10 randomly selected patches and calculating the average weight. The
individual weight should not deviate significantly from the average weight.

24. Drug content determination:
An accurately weighed portion of film (about 100 mg) is dissolved in 100 mL of
suitable solvent in which drug is soluble and then the solution is shaken
continuously for 24 h in shaker incubator. Then the whole solution is sonicated.
After sonication and subsequent filtration, drug in solution is estimated spectro-
photometrically by appropriate dilution
Content uniformity test: 10 patches are selected and content is
determined for individual patches. If 9 out of 10 patches have content between
85% to 115% of the specified value and one has content not less than 75% to
125% of the specified value, then transdermal patches pass the test of content
uniformity. But if 3 patches have content in the range of 75% to 125%, then
additional 20 patches are tested for drug content. If these 20 patches have range
from 85% to 115%, then the transdermal patches pass the test.

25. Moisture content: The prepared films are weighed individually and
kept in a desiccators containing calcium chloride at room temperature for 24 h.
The films are weighed again after a specified interval until they show a constant
weight. The percent moisture content is calculated using following formula.
% Moisture content = Initial weight – Final weight X 100
Moisture Uptake: Weighed films are kept in a desiccator at room
temperature for 24 h. These are then taken out and exposed to 84% relative
humidity using saturated solution of Potassium chloride in a desiccator until a
constant weight is achieved. % moisture uptake is calculated as given below.
% moisture uptake = Final weight – Initial weight X 100
Flatness: A transdermal patch should possess a smooth surface and
should not constrict with time. For flatness determination, one strip is cut from
the centre and two from each side of patches. The length of each strip is

26. Folding endurance: A strip of specific are is to be cut evenly and
repeatedly folded at the same place till it broke. The number of times the film
could be folded at the same place without breaking gave the value of the folding
endurance.
Tensile Strength: One end of the films is kept fixed with the help of
an iron screen and other end is connected to a freely movable thread over a
pulley. The weights are added gradually to the pan attached with the hanging
end of the thread. A pointer on the thread is used to measure the elongation of
the film. The weight just sufficient to break the film is noted.
Water Content: A test for water content should be included .
Microbial Limits: The type of microbial test(s) and acceptance criteria
should be based on the nature of the drug substance, method of manufacture
etc.
Sterility: Depending on the use of the dosage form, e.g., ophthalmic
preparations, sterility of the product should be demonstrated as appropriate

27. Viscosity: Rheological properties such as viscosity of semisolid dosage
forms can influence their drug delivery. Viscosity may directly influence the
diffusion rate of drug at the microstructural level.
Water vapour permeability (WVP) evaluation:
It can be determined with foam dressing method the air forced oven is replaced
by a natural air circulation oven.
Polariscope examination: This test is to be performed to examine
the drug crystals from patch by polariscope. A specific surface area of the piece
is to be kept on the object slide and observe for the drugs crystals to distinguish
whether the drug is present as crystalline form or amorphous form in the patch.
Adhesive properties
Shear Adhesion test: This test is to be performed for the
measurement of the cohesive strength of an adhesive polymer. It can be
influenced by the molecular weight
Tack properties: It is the ability of the polymer to adhere to substrate

28. Peel Adhesion test: In This test, the force required to remove an
adhesive coating form a test substrate is referred to as peel adhesion. A single
tape is applied to a stainless steel plate or a backing membrane of choice and
then tape is pulled from the substrate at a 180°C angle, and the force required
for tape removed is measured
Rolling ball test:

29. 2. a. In vitro release studies
The Paddle over Disc: This method is identical to the USP paddle
dissolution apparatus, except that the transdermal system is attached to a disc
or cell resting at the bottom of the vessel which contains medium at 32 ±5°C.
The Cylinder modified USP Basket: This method is similar to
the USP basket type dissolution apparatus, except that the system is attached to
the surface of a hollow cylinder immersed in medium at 32 ±5°C.
The reciprocating disc: In this method patches attached to holders
are oscillated in small volumes of medium, allowing the apparatus to be useful
for systems delivering low concentration of drug.
b. In vitro permeation studies
The amount of drug available for absorption to the systemic pool is greatly
dependent on drug release.
Horizontal-type skin permeation system: This has been
widely used for the evaluation of drug permeation across skin.

30. Franz diffusion cell: The cell is composed of two compartments:
donor and receptor. The receptor compartment has a volume of 5-12ml. The
diffusion buffer is continuously stirred at 600rpm by a magnetic bar. The
temperature in the bulk of the solution is maintained by circulating
thermostatic water through a water jacket that surrounds
the receptor compartment.
Flow-through diffusion cell: Flow through diffusion cells have the
advantage that they can be used when the drug has lower solubility in the
receptor compartment. This cell can be fully automated and connected directly
to HPLC.

31. 3. In vivo Studies
In vivo evaluations are the true depiction of the drug performance. The
variables which cannot be taken into account during in vitro studies can be
fully explored during in vivo studies. In vivo evaluation of TDDS can be
carried out using animal models human volunteers.
Animal models: The most common animal species used for evaluating
transdermal drug delivery system are mouse, hairless rat, hairless dog,
rabbit, guinea pig etc. Rhesus monkeyis one of the most reliable models for
in vivo evaluation of transdermal drug delivery in man.

32. Skin Irritation study
Skin irritation and sensitization testing can be performed on healthy rabbits
(average weight 1.2 to 1.5 kg). The dorsal surface (50cm2) of the rabbit is to be
cleaned and remove the hair from the clean dorsal surface by shaving and
clean the surface by using rectified spirit and the representative formulations
can be applied over the skin. The patch is to be removed after 24 hr. and the
skin is to be observed and classified into 5 grades on the basis of the severity
of skin injury.
Stability studies
Stability studies are to be conducted according to the ICH guidelines by
storing the TDDS samples at 40±0.5°c and 75±5% RH for 6 months. The
samples were withdrawn at 0, 30, 60, 90 and 180 days and analyse suitably
for the drug content.

33. Human models: The final stage of the development of a transdermal
device involves collection of pharmacokinetic and pharmaco-dynamic data
following application of the patch to human volunteers.
Clinical trials have been conducted to assess the efficacy, risk involved, side
effects, patient compliance etc.
Phase I clinical trials are conducted to determine mainly safety in volunteers
and phase II clinical trials determine short term safety and mainly
effectiveness in patients. PhaseIII trials indicate the safety and effectiveness in
large number of patient population and phase IV trials at post marketing
surveillance are done for marketed patches to detect adverse drug reactions.
Though human studies require considerable resources but they are the best to
assess the performance of the drug.

34. REFERENCES
 Transdermal Drug Delivery Technology
http://www.pharmainfo.net.
 Dispensing Pharmacy – RM MEHTA