The document discusses semisolid dosage forms and factors influencing dermal drug penetration. It defines various semisolid dosage forms including ointments, creams, gels and pastes. It then discusses biological, physicochemical and drug-related factors that influence how well drugs penetrate the skin. Key factors mentioned are skin condition, age, temperature, drug properties like solubility and molecular size. The document provides details on how each of these factors can impact dermal absorption of drugs administered via semisolid dosage forms.

1. Semisolid Dosage
Forms
Presented by:
Mr. Ahire E. D. M.S. PHARM
Assistant Professor,
Divine Collage of Pharmacy, Satana

2. Anatomy & Physiology
of Skin

3. Introduction
• The skin also known as cutaneous membrane or
integument, covers the external surface of the body
and protects the interior of the body.
• It is a sensory organ which is an largest organ of
the body in both surface area and weight.
• In adults skin covers an area about 2 sq.mts
( 22 sq.ft), weighs about 4.5 to 5 kgs and 16% of the
body weight.

4. • It is continuous with mucous membrane of body
orifices
• Evarage thikness is 1 to 2 mm.
• Eye lid - 0.5 mm
• Palm and soles - 6 mm
• pH – 4 to 5.6
• renewal of skin takes place in 28 to 50 days
Introduction

5. Skin changes according to age

6. Types of Skin
Two major classes of Skin
1. Hirsute – thin, hairy skin which covers grater part
of the body.
2. Glabrous – which covers the surfaces of palms,
soles and flexor surfaces of body.

7. Layers of Skin
Skin
Epidermis
Superficial layer
made up epithelia
Dermis
Deeper layer
Made up of
connective tissue

8. Structure of the skin
• Epidermis
– The superficial portion of the skin
– Composed of epithelial tissue.
• Dermis
– The deeper layer of the skin
– Primarily composed of connective tissue.
• Deep to the dermis is the subcutaneous layer
or hypodermis. (not a part of the skin)
– It consists of areolar and adipose tissue.
– fat storage, an area for blood vessel passage,
and an area of pressure sensing nerve
endings.

10. Layers of the Epidermis
From deepest to most superficial the layers of
the epidermis are
1. Stratum basale (stratum germinativum)
2. Stratum spinosum
3. Stratum granulosum
4. Stratum lucidum (only in palms and soles)
5. Stratum corneum

12. Stratum Basale
(stratum germinativum)
• Deepest single layer of epidermis
– merkel cells, melanocytes,
keratinocytes & stem cells that
divide repeatedly
– keratinocytes have a cytoskeleton
of tonofilaments
– Cells attached to each other &
to basement membrane by
desmosomes &
hemidesmosomes
• When the germinal portion of the
epidermis is destroyed, new skin
cannot regenerate with a skin graft.

13. Stratum Spinosum
• Provides strength and
flexibility to the skin
• 8 to 10 cell layers are
• Held together by
desmosomes.

14. Stratum Granulosum
• transition between the
deeper, metabolically
active strata and the
dead cells of the more
superficial strata
• 3-5 layers of flat dying
cells that show nuclear
degeneration
• example of apoptosis
• Contain lamellar
granules that release
lipid that repels water
• Contain dark-staining
keratohyalin granules.
keratohyalin converts
tonofilaments into keratin

15. Stratum Lucidum
• present only in the
fingers tips, palms of
the hands, and soles
of the feet.
• Three to five layers
of clear, flat, dead
cells
• Contains precursor
of keratin

16. Stratum Corneum
• 25 to 30 layers of flat
dead cells filled with
keratin and surrounded
by lipids – continuously
shed
• Barrier to light, heat,
water, chemicals &
bacteria
• Lamellar granules in this
layer make it water-
repellent.
• Where callus, an
abnormal thickening of
the epidermis, is
formed.

17. Keratinization and Growth of the
Epidermis
• Stem cells divide to produce keratinocytes
• As keratinocytes are pushed up towards the surface,
they fill with keratin.
- Keratinization is replacement of cell contents with
the protein keratin; occurs as cells move to the skin
surface over 2-4 weeks in 1 mm of skin
• Epidermal growth factor (EGF) and other hormone-
like proteins play a role in epidermal growth.
• Nutrients & oxygen diffuse to the avascular
epidermis from blood vessels of dermis.

18. Four Principle Cells of the Epidermis
• Keratinocytes
– produce the protein keratin, which helps protect the
skin and underlying tissue from heat, microbes, and
chemicals, and lamellar granules, which release a
waterproof sealant
• Melanocytes
– produce the pigment melanin which contributes to
skin color and absorbs damaging ultraviolet (UV)
light
• Langerhans cells
–
–
derived from bone marrow
participate in immune response
• Merkel cells
– contact a sensory structure called a tactile (Merkel) disc
and function in the sensation of touch

19. Four Principle Cells of the Epidermis

20. Dermis
• Connective tissue layer
composed of collagen &
elastic fibers, fibroblasts,
macrophages & fat cells
• Contains glands, hair follicles,
nerves & blood vessels
• Two major regions of dermis
– papillary region
– reticular region

21. Dermis - Papillary Region
• Top 20% of dermis.
• Finger like projections are called dermal
papillae anchors epidermis to dermis.
• contains capillaries that feed epidermis.
• contains Meissner’s corpuscles in the dermis near
dermoepidermo jn. Detection of sensations of
touch, shape and texture.
• Pacinians corpuscles- deep pressure and
vibrational sensations.
• Free nerve endings for sensations of heat, cold,
pain, tickle, and itch.

22. Dermis - Reticular Region
• Dense irregular connective tissue.
• Contains interlacing collagen and elastic fibers.
• Packed with sebaceous glands, sweat gland ducts, fat &
hair follicles.
• Provides strength, extensibility & elasticity to skin.

24. Accessory Structures of Skin
• develop from the
embryonic epidermis
• Cells sink inward
during development
to form:
– hair
– oil & sweat glands
– nails

25. Glands of the Skin
Specialized exocrine glands found in
dermis are
• Sebaceous (oil) glands
• Sudoriferous (sweat) gland
• Ceruminous (wax) glands
• Mammary (milk) glands

26. Sebaceous (oil) glands
• Sebaceous (oil) glands are usually connected to
hair follicles; they are absent in the palms and
soles
• Produce sebum
– contains cholesterol, proteins, fats & salts
– moistens hairs
– waterproofs and softens the skin
– inhibits growth of bacteria & fungi (ringworm)
• Acne
– bacterial inflammation of glands
– secretions are stimulated by hormones at puberty

27. Sebaceous gland

28. Sudoriferous (sweat) glands
• Eccrine sweat glands (most areas of skin)
– regulate body temperature through
evaporation (perspiration)
– help eliminate wastes such as urea.
• Apocrine sweat glands (skin of the axilla, pubis,
and labia minora)
– secretions are more viscous

29. Ceruminous Glands
• Ceruminous glands
– produce a waxy substance called
cerumen.
– found in the external auditory meatus
– barrier for entrance of foreign bodies

30. Shaft – visible
Root - below the surface
Follicle –
- surrounds root
- external root sheath
- internal root sheath
- base of follicle is bulb
- blood vessels
- germinal cell layer

31. Hair Related Structures
Arrector pili
– Smooth muscle in
dermis contracts
with cold or fear.
– forms goosebumps
as hair is pulled
vertically
• Hair root plexus
– detect hair movement
• sebaceous (oil)
glands

32. Structure of Nails
• Tightly packed
keratinized cells
• Nail body
– visible portion pink due to
underlying capillaries
– free edge appears white
• Nail root
– buried under skin layers
– lunula is white due to
thickened stratum basale
• Eponychium (cuticle)
– stratum corneum layer

33. Functions of skin
• Protection
• Thermoregulation
• Sensation
• Vitamin D synthesis
• Excretion & Absorption
• Psychological and social
function

34. Protection
• Physical, chemical and biological barriers
• Tight cell junctions prevent bacterial invasion
• Lipids released retard evaporation
• Pigment protects somewhat against UV light
• Langerhans cells alert immune system

35. Thermoregulation
• Perspiration & its evaporation
– lowers body temperature
– flow of blood in the dermis is adjusted
• Exercise
– in moderate exercise, more blood brought
to surface helps lower temperature
– with extreme exercise, blood is shunted
to muscles and body temperature rises
• Shivering and constriction of surface vessels
– raise internal body temperature as needed

36. Cutaneous Sensations
• Touch,
• Pressure,
• Vibration,
• Tickle,
• Heat& Cold (Thermal)
• Pain & Itch (Noxious)

37. Synthesis of Vitamin D
• Activation of a precursor molecule in the skin by
UV light
• Enzymes in the liver and kidneys modify the
activated molecule to produce calcitriol, the most
active form of vitamin D.
• Necessary vitamin for absorption of calcium from
food in the gastrointestinal tract

38. Excretion & Absorption
Excretion
• 400 ml of water/day,
• Small amounts Nacl,
• CO2,
• Ammonia and Urea
Absorption
• Water soluble compo. –
Negligible
• Lipid soluble Vitamins -
A, D, E, K
• Organic solvents
• Heavy metals
• Topical medicines

39. Types of semisolid
dosage forms

40. Semisolid dosage forms
Ointment
Creams
Paste
Gels

41. Ointments
Semisolid preparations intended for external
application to the skin or mucous membranes.
Semisolid plastic flow characteristics
Definite yield value
Eg. Cold Cream (Petrolatum-Rose Water Ointment)
Lanolin , Nivea, Eucerin

42. Creams
Opaque, soft solids, or thick liquids intended
for external application.
Semisolid, pseudoplastic flow
Very little yield value
Won’t flow under force of gravity but small
force will initiate flow
Viscous liquids or semisolid emulsions of
either the O/W type or the W/O type
Term “cream” is most frequently applied
to soft, cosmetically acceptable types of
preparations.

43. Gels
Semisolid systems consisting of dispersions of
small or large molecules in an aqueous liquid
vehicle rendered jelly-like through the addition
of a gelling agent
A semi-rigid system in which the movement of
the dispersing medium is restricted by an
interlacing network of particles or solvated
macromolecules of the dispersed phase

44. Pastes
Pastes are semisolid dosage forms that contain
one or more drug substances intended for topical
application.
One class is made from a single-phase aqueous
gel (e.g. Carboxymethylcellulose Sodium Paste)
It consists of fatty base (e.g., petroleum jelly)
and at least 25% solid substance (e.g., zinc oxide).
Pastes are the semisolid preparations intended
for external application to the skin. Usually they
are thick and do not melt at normal temperature.

45. Factors influencing dermal
penetration of drugs
II. Physicochemical factors:
1. Skin hydration
2. Temperature and pH
3. Diffusion coefficient
4. Drug concentration
5. Partition coefficient
6. Molecular size and shape
I. Biological / patient
factors:
1. Skin condition
2. Skin age
3. Blood flow
4. Regional skin site
5. Skin metabolism
6. Species difference.

46. Factors influencing dermal
penetration of drugs
III. Drug related factors:
1. Drug solubility
2. Particle Size
3. Nature of the base

47. Patient Related factors:
1. Skin condition
The intact, healthy skin is a tough barrier but acids and
alkalis injure barrier cells and thereby promote penetration
Mixtures of non-polar and polar solvents, such as chloroform
and methanol, remove the lipid fraction and molecules pass
more easily.
Disease alters skin condition, skin inflamed, with loss of
stratum corneum thus permeability increases.
2. Skin age
Skin of the young and the elderly is more permeable than
adult tissue.
Children are more susceptible to the toxic effects of drugs
and chemicals, because of their greater surface area per unit
body weight; thus potent topical steroids, Causes severe side-
effects and death.

48. 3.Blood flow:
An increased blood flow could reduce the amount of time
a penetrant remains in the dermis, and also raise the
concentration gradient across the skin.
In clinically hyperaemic disease damages the skin
barrier and increase absorption
4. Regional skin sites :
Variations in permeability depend on the thickness and
nature of the stratum corneum and the density of skin
Absorption changes with substance, volunteer and site.
Permeabilities depend on thickness of stratum corneum
and the overall thickness of the tissue.
Plantar and palmar callus may be 400-600 µm thick
compared to 10-20 µm for other sites
Facial skin in general is more permeable than other body
sites

49. 5.Skin metabolism:
The skin metabolizes steroid hormones, chemical
carcinogens and some drugs. This is advantage to
prodrugs. Skin can metabolize 5% of topical drugs.
6.Species differences:
Mice, rats and rabbits are used to assess percutaneous
absorption, but their skins have more hair follicles than
human skin and they lack sweat glands.

50. Physicochemical factors
1. Skin hydration
When water saturates the skin the tissue swells, softens and
wrinkles and hydration of the stratum corneum increases
permeability
Dusting powders or lotions, provide a large surface
area for evaporation and therefore dry the skin
2. Temperature and pH
The penetration rate of material through human skin can
change tenfold for a large temperature variation.
Occlusive vehicles increase skin temperature and
increase permeability.
According to pH-partition hypothesis, only unionized
molecules pass readily across lipid membranes.
Stratum corneum is resistant to alterations in pH, range of 3-9.

51. 3. Diffusion coefficient
The diffusional speed of a molecule depends mainly on
the state of matter of the medium.
In gases, diffusion coefficients are large than liquids
In skin, the diffusivities reach their lowest values
within the compacted stratum corneum matrix.
The diffusion coefficient of a drug in a topical vehicle
depends on the properties of the drug and the diffusion
medium and on the interaction between them.
4. Drug concentration:
Drug permeation and flux of solute is proportional to the
concentration gradient across the barrier.
drug permeation follows Fick's law, saturated donor
solution gives maximum flux.
pH change, complex formation, or the presence of
surfactants, micelles or cosolvents modify the
effective partition coefficient

52. 5. Partition coefficient(K):
The partition coefficient is important in establishing the flux of
a drug through the stratum corneum.
Drug are water soluble, are oil soluble.
Polar cosolvent mixtures, such as propylene glycol with
water, produce saturated drug solutions and maximize the
concentration gradient across the stratum corneum.
Surfactants disruption of intercellular lipid packing in the
stratum corneum, act as penetration Enhancers.
Complex formation of drug increases the apparent
partition coefficient may promote drug absorption.
6. Molecular size and shape
Absorption is apparently inversely related to molecular
weight. Small molecules penetrate faster than large ones.
It is more difficult to determine the effect of molecular shape,
as it is related to partition coefficient.

53. III. Drug related Factors
1- Drug solubility in vehicle:
- The rate at which a drug is released from a Solid
dosage form and absorbed by the membrane is
directly related to its solubility in the vehicle or, in
other words, to the partition coefficient of the drug
between the vehicle and the membrane.
2- Particle Size:
- For drugs present in a solid dosage form in the
undissolved state, the size of the drug particle will
influence its rate of dissolution and its availability for
absorption.
3- Nature of the base:
- The base must be capable of melting, softening, or
dissolving to release its drug components for
absorption.

54. Formulation of
semisolids

55. Ingredients :
Active pharmaceutical
ingredients
Bases
Preservatives
Humectants
Anti oxidants
Emulsifier
Gelling agent
Permeation enhancer
Buffers
Semisolid Bases and
Additives

56. API Selection

57. The skin is an evolutionary masterpiece of living tissue
which is the final control unit for determining the local and
systemic availability of any drug which must pass into and
through it.
In vivo in humans, many factors will affect the
absorption of drugs. These include individual biological
variation and may be influenced by race.
The skin site of the body will also influence percuta-
neous absorption. Generally, those body parts exposed to
the open environment (and to cosmetics, drugs and
hazardous toxic substances) are most affected.
Percutaneous Absorption

60. It is one of the most important ingredient used in
the formulation of semisolid dosage form
Ointments and suppository base do not only acts
as the carrier of the medicaments, but they also
control the extent of absorbtion of medicaments
incorporated with them
Bases

61. 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.
Ideal properties of Bases

62. BASES
OLEAGENOUS
BASE
ABSORBTION
BASE
EMULSION
BASE
WATER
SOLUBLE
BASE

63. 1. Oleaginous ( hydrocarbon) bases
They consist of a combination of more than one
oleaginous material such as water insoluble hydrophobic
oils and fats
They are highly compatible ; occlusive ; good emollients
They are anhydrous, do not absorb water, readily
(hydrophobic) insoluble in water, non washable
Example : Vaseline,hard parafin, liquid paraffin,white
ointment.
Uses : protective, emollient and vehicle for solid drugs.

64. 2. Absorption (Emulsifiable) base
Have capacity to absorb considerable quantities of
water or aqueous solution and turns to w/o without
marked changes in the consistency.
They are anhydrous, water insoluble and water
unwashable.
They have good emollient but poor occlusive
property.
Uses: protective, emollient and vehicle for aqueous
solutions and solid drug.

65. 3. Emulsion bases
According to the type of emulsion these bases are
classified as either W/O or O/W.
W/O EMULSION
BASE
O/W EMULSION
BASE
Hydrous Hydrous
Will absorb water Will absorb water
Insoluble in water Insoluble in water
Not washable washable

66. 4. Water soluble Bases
These include both hydrous and non hydrous
dermatological non- emulsion bases which are
water soluble and contain no oil phase.
 Water soluble, water washable, non greasable
Because they softens with the addition of water,
large amount of aqueous solutions are not
effectively incorporated into the bases.
Example : carbowax compounds such as the
poly ethylene glycol bases containing pectin,
cellulose, bentonite and gelatin.

67. Some bases , although, resist microbial attack but
because of their high water content, it require an anti
microbial preservative.
Commonly used preservativeinclude:
Methyl hydroxy benzoate
Propyl hydroxy benzoate
Chlorocresol
Benzoicacid
Phenyl mercuricnitrate
Preservatives

68. Oxygen is highly reactive atom that is capable of
becoming of potentially damaging molecules
commonly called “free radicals”
Free radicals are capable of attacking the healthy
cells of the body, causing them to loose their structure
and functions to prevent this an anti oxidant are added
Example : Butylatedhydroxy anisole , Butylated
hydroxy toluene
Antioxidants

69. CLASSIFICATION OFANTIOXIDANT
ANTIOXIGENS REDUCING
AGENT
ANTIOXIDANT
SYNERGIST
Acts by reacting with
the free radicals.
e.g.
•Butylated hydroxy
anisole (BHA)
•Butylated hydroxy
tocopherols (BHT)
(used for oil system)
Have lower redox
potential than
drug,hence gets
oxidized first.
e.g.
•Ascorbic acid
•Potassium and
sodium metabisulfite
•Thiosulfite
(used for aqueous
system)
Chelating or
sequestering
agents, enhance the
effect of anti
oxidants.
e.g.
•Citric acid
•Tartaric acid
•Lacithin

70. Gelling agents
 Gelling agent forms a gel dissolves in a liquid phase as
a colloid mixture that forms a weakly cohesive internal
structure.
 These are organic hydro colloids or hydro phillic
inorganic substances
Example : tragacanth, sodium alginate, pectin, gelatin,
cellulose derivatives.
Material % Brook field
viscosity
Carbomer 94 1 resin NF 0.15 2900
Carbomer 94 1 resin NF 0.25 6300
Guar gum 1.50 8040
Methyl cellulose 2.00 5200
Sodium alginate 2.50 10400

71. Permeation enhancer
Skin can acts as a barrier with the introduction of
various penetration enhancers, penetration of the
drug through the skin can be improved.
Permeation enhancer Drug used
Methanol,carvacrol,
linalool
Propranolol
hydrochloride
Limonene Indomethacin ,
ketoprofin
Geraniol
Nerolidol
Diclofenic sodium
Oleic acid Piroxicam

72. Anionic Cationic Non ionic
•Alkyl sulphates •Quaternary •Polyoxyethylene
•Soaps ammonium •Alkyl-aryl ethers
•D odecyl benzene compounds •Polyoxy ethylene
•Sulfonates •alkoxyalkylamines •Sorbitan esters
•Lactylates •Sorbitan fatty acid
•Sulfosuccinates esters
•Monoglycerides •Glyceryl fatty acid
•Sulfonates esters
•Phosphate esters
•Silicones
•Taurates
Emulsifier

73. A humectant is a hygroscopic substance . It is often a
molecule with several hydrophilic groups, most often
hydroxyl group.
Humectants are used to:
 Increase the solubility of active ingredients
 To elevate its skinpreparation
 Elevate the hydration of the skin.
Humectants

74. Buffers are added to variopus purpose such as:
Compatibility with skin
Drug solubility
Drug Stability
Influence on ionization of drug
Example: Sodium acetate , Sodium Citrate ,
Potassium meta phosphate
Buffers

75. Purified water
Water for Injection
Water for injection may be used in ophthalmic semi
solid preparation like eye ointments , gels etc
Vehicles

76. Preparation Methods

77. 1.Trituration Method
Widely used method
For extemporaneous preparation of ointments. When the
base is soft and medicament is solid insoluble, small amount
of liquid to incorporated in the base
Advantage: Involves mixing as well as size reduction
Procedure:
1. Reduce the solid medicament to fine powder
2. Medicament is mixed with small amount of base on
ointment slab with a stainless steel spatula until a
homogeneous product is formed.
3.Add remaining quantities of base with uniform mixing
4.Incorporate any liquid ingredient if present

78. 2. Fusion method
Suitable when ointment base contains number of solid
ingredients of different melting points.
Procedure:
1. Ointment base are melted in decreasing order of their
melting point.
2. Highest melting point should be melted first, low melting
point next.
3. This avoids over heating of substances of low melting point
4. Incorporate medicament slowly to the melted mass
5. Stir thoroughly until mass cools down and
homogeneous product is formed.

79. 6. Liquid ingredients or aqueous substance should be
heated to the same temperature as the melted bases
before addition.
7. If not, wax or solids will cool down quickly and get
separated
Precautions:
Strring is done continously- homogeneous mass
Vigorous stirring should be avoided to prevent entrapment
of air
Rapid cooling should be avoided to get a uniform product
Toremove the dust or foreign particles strain through
muslin cloth

80. 3. Chemical reaction method
Preparation of some ointment involves chemical reactions
Eg – (a)Iodine ointment (iodine free form)
(b)Iodine ointment (iodine +ointment)
(a)Ointments containing free iodine
Iodine is slightly soluble in fats and vegetable oils.
Readily soluble is potassium iodide solution in water due to
formation of poly-iodides
Poly iodides are readily soluble in water, alcohol and glycerin.
These solutions may be incorporated with the molten absorption
type ointment base

81. (b) Ointments containing combined iodine
Fixed oils and many fats obtained from vegetable and animal
sources contain unsaturated constituents Iodine combines
with double bonds
CH3 (CH2)7 CH=CH (CH2)7 COOH + I2 (Oleic acid)
CH3 (CH2)7 CHI.CHI (CH2)7 COOH (Di-iodo stearic acid)
Free iodine is not available, So ointments appear dark, greenish
black in colour leaves no stain when rubbed into the skin,
Hence known as non- staining iodine ointment

82. 4. Emulsification method
1. Fats, oils and waxes are melted together to a temperature
at 700c.
2. Aqueous solution of the heat stable, water soluble
compounds are also heated to the same temperature
3. Solution is slowly added to the melted bases, with
continuous stirring until cool
•Emulsifying agent is needed to make a stable emulsion
•Water soluble soaps are commonly used as emulsifier for
semisolid o/w emulsions.
•Combination of tri-ethanolamine stearate soap and cetyl
alcohol is used in o/w emulsion Bees wax and divalent
calcium ions used in w/o emulsion.

83. Laboratory Scale
1. Ointment slab & spatula
2. Motor & pestle
3. Electric motor & pestle

84. Industrial Scale:
Ointment mill, Triple roller mill, Hobart type mixer

85. Packing of ointment
• Ointment jars
• Made of colorless or colored glass
• Amber colored for light sensitive
preparation
• with screw caps
• with impermeable liners
• Collapsible tubes
• Made of tin or plastic
• Supplied with the applicator

86. Storage
Store in a well closed container and in cool place
Protect from high temperature/ direct sunlight
Prevent the loss of volatile constituents
High temperature soften or melt base
Separation of phases may take place
Labeling:
“ FOR EXTERNAL USE ONLY ”

87. Evaluation of Semisolid
Dosage forms
 Content uniformity of drug
 Penetration/Permeation
 Rate of release of medicament
 Absorption of medicament in blood stream
 Skin Irritation test
 Viscosity
 Extrudability
 Globule size
 PH
 Spreadability

88.  Content uniformity of drug
A known weight of ointment is taken and
assayed for amount of the drug.
 Penetration
A weighed quantity of ointment is rubbed over
skin for a given period of time and unabsorbed
ointment is collected and weighed.
The differences in weights represent the amount
absorbed.

89. In Vitro Skin Penetration
 Flow through cell
 Franz diffusion cell
They mainly have two compartments
1) Donor
2) Receptor
Method:
 mouse skin or human cadaver skin.
 Placed in between the two compartments.
 The passage of semisolid preparation through
the epidermal surface to receptor compartment
is measured by,
 Detector ( Flow through type )
 Sampling ( Franz diffusion cell )

90. Rate of release of
medicament
 To assess rate of release of medicament, small
amount of the ointment can be placed on the
surface of nutrient agar contained in a Petri dish or
alternately in a small cup cut in the agar surface.
 If the medicament is bactericidal the agar plate is
previously seeded with a suitable organism like
s.aureus. After a suitable period of incubation, the
zone of inhibition is measured and correlated with
the rate of release.
 Another method for finding out release rate is to
smear internal surface of test tubes with thin
layers of ointment, fill the tubes with saline/serum
and after a gap of time estimating the amount of
drug present in the serum/saline

91. Absorption of medicament into
blood stream
 The diadermatic ointment should be evaluated
for the rate of absorption of drug into the blood
stream. This test can be run in-vivo only.
 Definite amount of ointments should be rubbed
through the skin. Under standard conditions
and medicaments are estimated in the blood
plasma or urine.

92. Skin Irritation Test
 In general no ointment should possess irritant
effect on the skin or mucous membranes the
tests for irritancy can be carried out on the skin
and eyes of rabbits or the skin of human beings.
 The irritant effect can also be judged to a certain
extent by injecting the ointment into thigh
muscles and under the abdominal skin of rats.
Reaction are noted at intervals of 24,48,72 and
96 hours. Lesions on cornea, iris, conjunctiva
are used for judging the irritancy to the eyes.

93. Draize Test
 Draize skin irritation test:
 A known amount of test substance is introduced
under a one square inch gauge patch,
 The patch is applied to skin of 12 albino rabbits,
(6 with intact skin) and (6 with abraded skin),
 The patch is secured in place with adhesive
tape and the entire trunk of the animal is
wrapped with an impervious material for a 24
hour period,
 After 24 hours the patches are removed and
resulting reaction is evaluated for erythema and
edema formation.
 The reaction is again scored at the end of 72
hours and the two readings are averaged.

94. Category
Draize
Code Skin reaction
Mild MLD Well defined erythema and slight
edema ( edges of area well defined
by definite raising)
Moderate MOD Moderate to severe erythema and
moderate edema (area raised
approximately 1 mm)
Severe SEV Severe erythema (beet redness to
slight formation (injuries in depth )
and severe edema ( raised more
than the 1 mm and extending
Conclusion From Draize test

95. Draize eye irritation test
 A known amount of test material is placed in one
eye of each of 6 albino rabbits the other eye
remains untreated, serving as a control.
 The eyes are not washed after instillation and
are examined at 24,48 and 72 hours for ocular
reaction.
 The test is considered positive if ulceration,
opacity of the cornea , inflammation of the iris,
swelling of the conjunctiva occurs.
 A substance is an eye irritant
 4 of six rabbits score positive
 it is considered a non irritant if none or only one of the
6 animals exhibit irritation

96. HET cam test
 The Hen's Egg Test (HET) is well known as a basic
test for embryotoxicity and for special aspects of
systemic toxicity and immuno- pathology
 The HET embryotoxicity test has been extended and
standardized as the HET-chorioallantoic membrane
(CAM) test for membrane irritation
 The CAM of fertile White Leghorn eggs incubated
for 10 days is a vital vascular membrane, in which
irritant effects can be observed.

97. Viscosity
 Rheology is very important as these semisolids are
marketed in tubes or containers. The Rheology or
viscosity should remain constant.
 Viscosity can be measured using Brookfield
viscometers is used for such formulations

98. Extrudability
 A simple method was adopted for determination of
extrudability in terms of weight in grams required to
extrude a 0.5cm ribbon of gel in 10 seconds from the
collapsible tube.

99. Globule size
 This can be determined by microscopic study of the
globules
 Take a small quantity of formulation and dissolve it in
a solvent. Take few droplets on slide and observed
under microscope

100. pH
 The pH of semisolids were determined by digital pH
meter .
 One gram of formulation was dissolved in 100ml of
distilled water and stored at 4°C for two hours
 After 2 hours, take formulation and determine its pH

101. Spreadability
 A modified apparatus consisting of two glass slides
containing formulation in between with the lower
slide fixed to a wooden plate and the upper one
attached to a balance by a hook was used to
determine spreadability