M 4 Lesson 1: Semi-solids (1/3)
Moisturizing Factor) from being
Ointments, creams, paste and gels are semisolid
dosage forms intended for topical application. Most
of these preparations are medicated while others
are non-medicated used as protectants or lubricants.
Topical preparations are used for both local and
systemic effects, whose main route is the biggest
organ of the boy which is the skin
Drug Transport and Permeation Through the Skin
The main drug transportation route of the semi solid
dosage form, is our skin. When a drug is applied
topically, the drug diffuses out of its vehicle onto the
surface of the skin.
The drug molecules have three routes to traverse
the intact stratum corneum depending on their
physicochemical properties, these being:
Intracellular (across corneocytes)
Intercellular (across lipids) considered the major
route of penetration
Appendageal (via skin appendages)
Factors Influencing Drug Absorption through the Skin
1. Partition Coefficient of Drugs through the Skin
Drugs with both water and lipid solubility are
favorably absorbed through the skin.
2. Moisture and Temperature in the Environment of
the Skin
 Moisture Balance in the Skin
o It is found in the stratum corneum
layer of the epidermis.
o It prevents the NMF (Natural
stripped from the skin.
o NMF prevents skin from drying out,
even during excessive contact of
the skin with water.
 Insensible Perspiration
o The skin constantly releases water
in the skin surface, which
evaporates quickly without being
noticed.
o When the surrounding
environment has a high moisture
content, the rate of evaporation of
sweat is slowed down, and the
person becomes aware of the
clammy moist sensation on his
skin.
3. Pathological Injury to the Skin
 Skin penetration has been enhanced by
abrasions or when the skin is stripped of its
barrier layer.
4. Type of Vehicle Used Skin
 Penetration of drug substances may be
enhanced by the use of a suitable semi solid
base.
 The vehicle may help increase the rate of
penetration of drug substances into the
skin.
 It serves as a carrier for the API.
M 4 Lesson 1: Semi-solids (2/3)
Starting Material and Vehicle
FDA approves chemical substances and states the
maximum concentration considered safe for food
and cosmetics (GRAS grade/ generally regarded or
recognized as safe ingredients).
The supplier of these drug substances supplies
brochures / information which indicates that FDA
APPROVAL SAFETY TESTS are conducted.
THE FREQUENT STARTING MATERIALS FOR
MEDICATED SEMI-SOLIDS

Factors which influence the choice of semisolid
vehicles/base
 Nature of the skin lesion
 Skin type
 Solubility of the formulation components
 Stability of the API’s
M 4 Lesson 1: Semi-solids (3/3)
Starting Materials -Miscellaneous Excipients
OPHTHALMIC OINTMENTS
 Semisolid ophthalmic vehicles frequently
contain any of the ff. bases that have been
sterilized;
1. Petroleum jelly
2. Absorption base (Lanolin or Lanolin Alcohol)
3. Water-soluble base
4. Other ophthalmic ointment bases
 Lanolin sterilized by gamma radiation or
sterilization by filtration
 Lanolin alcohol possesses emollient
properties suitable for eye ointment
formulation.
 Insoluble API powders should meet the
requirements for IMPALPABILITY
 Ophthalmic ointments should be rendered
STERILE and ISOTONIC
PRESERVATION FROM MICROBIAL SPOILAGE
The chemical preservative for semisolids should be
evaluated as to:
1. Stability with regard to formulation
components
2. Container to be used
CHARACTERISTICS OF PRESERVATIVES FOR
SEMISOLID PRODUCTS
 Some preservatives become inactive in the
presence of other ingredients.
 Boric acid may be used in ophthalmic
ointments against bacterial/ fungal
contamination.
 Bacterial counts should be made on the (1)
water supply, (2) starting materials, (3)
pipelines, (4) filling equipment and (5)
containers.
USE OF ANTI-OXIDANTS
Anti-oxidants are added to semisolids, whenever
oxidative deterioration is anticipated.
 BHA, BHT, Propyl gallate
The choice of anti-oxidant is made upon
consideration of the following factors:
1. Toxicity / irritating potency
2. Compatibility
3. Odor
4. Discoloration
5. Solubility
6. Stability
M 4 Lesson 2: Manufacturing of Semi-solids (1/2)
EVALUATION OF MEDICATED APPLICATIONS M 4 Lesson 2: Manufacturing of Semi-solids (2/2)
EVALUATION OF MEDICATED APPLICATIONS AS PER
FUSION METHOD USP REQUIREMENTS
 ANHYDROUS OINTMENTS are manufactured
by this process, which is made by dissolving STORAGE and LABELING
the API’s in the previously melted fats and MICROBIAL SCREENING (Microbial Limit Tests)
waxes.  Staphylococcus aureus
 The melted mass must be mixed while  Pseudomonas aeruginosa
cooling to ensure the homogenous MINIMUM FILL
distribution of the ingredients.  Assessment of the Content Uniformity of
 If a perfume or volatile oil is added it is best semi-solids.
done at temperature 40-43°C o For product weighing 60 g or mL:
NLT 90% of the labeled amount.
Factors to be controlled during the Fusion Method: o For product weighing 60 g or mL to
1. Time of mixing 150 g or mL: NLT 95% of the
2. Temperature of mixing labeled amount.
3. Rate of agitation (and other mechanical STANDARD ASSAYS of the API’s (Quantitative assay
works) of % Purity or % Content)
STERILITY TESTS
1. Membrane Filtration Technique
2. Test Tube Inoculation Method
In vivo BA/BE – Dermatopharmacokinetic Studies
(DPS)
 Applicable to semisolids that contain:
1. Antifungals
2. Antivirals
3. Corticosteroids
4. Antibiotics
5. Topicals for vaginal use
 Not applicable to semisolids for;
1. Otic use
2. Opthalmic use
3. That damage the stratum corneum of the
skin.
 It involves measurement of the ff.;
1. Drug concentration in the stratum corneum
2. Drug uptake
3. Apparent steady state
4. Elimination after drug application onto the
skin
METHODS OF FILLING OPTHALMIC OINTMENTS
EVALUATION OF MEDICATED APPLICATIONS AS PER
 BLOW FILL SEAL METHOD (BFS) SEQUENCE NON-USP REQUIREMENTS
in ONE EASY OPERATION:
1. Fabrication of containers 1. pH
2. Filling the product 2. Water Content (Karl Fischer Method) Water
3. Sealing affects the;
 physical stability
 FORM FILL SEAL METHOD (FFS) The  chemical stability
conventional method of filling ophthalmic  microbial stability
ointments. 3. Usual water limit: 0.5% to 1%
4. NMT 0.5% water content for Ointments 11. If 1 tube leaks, repeat the test on 20
containing: additional tubes.
a. Bacitracin  Requirements are met if:
b. Chlortetracycline HCl  NMT 1 tube out of the 30 tubes should leak
c. Nystatin
5. NMT 1% water content for ointments,
creams or gels containing;
a. Erythromycin
b. Gentamycin sulfate
c. Neomycin sulfate
d. Tetracycline HCl
6. Foreign Substances
 Introduced by contamination or
adulteration and not a consequence of the
synthesis or preparation of compendial
articles
7. Homogeneity (also refers to Content
Uniformity by Minimum Fill testing)
8. Metal Particle Detection Test
 Mandatory for ophthalmic ointments only.
 Procedure
a. Count the number of metal particles that
are 50 μm or larger in any dimension: the
requirements are met if the total number of
such particles in all 10 tubes does not
exceed 50, and if not more than 1 tube is
found to contain more than 8 such particles.
b. If these results are not obtained, repeat the
test on 20 additional tubes: the
requirements are met if the total number of
metal particles that are 50 μm or larger in
any dimension does not exceed 150 in all 30
tubes tested, and if not more than 3 of the
tubes are found to contain more than 8
such particles each
9. Leaker Test
 Mandatory for ophthalmic ointments
filled in collapsible tubes.
 By Classical Blotting Paper Method
 Procedure
a. Select 10 tubes of the ointment, with
seals applied
b. Place the tube in a horizontal position
on a sheet of absorbent blotting paper
in an oven maintained at temperature
of 60 ± 3 degrees Celsius for 8 hours.
10. Specs / Limits:
 Requirements are met if:
 Out of the first 10 tubes tested, NO
LEAK is observed.