Introduction, structure of skin, mechanism & penetration of drug through skin, ointments, cream, paste, gels, evaluation test for semisolid

1. SEMISOLID DOSAGE FORM
Mr. R. R. Patil
Dr. Shivajirao Kadam College of Pharmacy, Kasabe Digraj, Sangli

2. INTRODUCTION
 DEFINITION:
Semi solids are the topical dosage form
used for the therapeutic, protective or
cosmetic function. They may be applied
to the skin, or used nasally, vaginally, or
rectally…

3.  Pharmaceutical semisolid dosage
preparations include :ointments, pastes,
cream, plasters, gels etc..
 They contain one or more active ingredients
dissolved or uniformly dispersed in a suitable
base and any suitable excipients such as
emulsifiers, viscosity increasing agents, anti
microbial agents, antioxidants, or stabilizing
agents etc..

4. ADVANTAGE OF SEMI-SOLID DOSAGE
FORM
 It is used externally
 Probability of side effect can be reduce
 First pass gut and hepatic metabolism is
avoided.
 Local action and Site specific action of drug
on affected area.
 Convenient for unconscious patient or
patient having difficulty on oral administration.
 Suitable dosage form for bitter drugs.
 More stable than liquid dosage form

5. DISADVANTAGES OF SEMI-SOLID DOSAGE
FORM
 There is no dosage accuracy in this type of
dosage form
 The base which is used in the semi-solid
dosage form can be easily oxidized.
 May cause staining.
 They are bulky to handle.
 Application with finger may cause
contamination.
 Physico-chemically less stable than solid
dosage form.
 May cause irritation or allergy to some
patients

6. IDEAL PROPERTIES OF SEMISOLIDS
PHYSICAL PROPERTIES:
 Smooth texture
 Elegant in appearance
 Non dehydrating
 Non gritty
 Non greasy and non staining
 Non hygroscopic

7. PHYSIOLOGICAL PROPERTIES
 Non irritating
 Do not alter membrane / skin functioning
 Miscible with skin secretion
APPLICATION PROPERTIES
 Easily applicable with efficient drug release.
 High aqueous wash ability.

8. STRUCTURE OF SKIN

9.  Skin is composed of three primary layers: the
epidermis, the dermis and the hypodermis.
EPIDERMIS
 Epidermis is the outermost layer of the skin.
 It forms the waterproof, protective wrap over
the body's surface which also serves as a
barrier to infection.
 The epidermis contains no blood vessels, and
cells in the deepest layers are nourished
almost exclusively by diffused oxygen from
the surrounding air.

10. EPIDERMIS IS DIVIDED INTO THE
FOLLOWING 5 SUB LAYERS
 Stratum corneum
 Stratum lucidum
 Stratum granulosum
 Stratum spinosum
 Stratum basale

12. STRATUM CORNEUM
 The stratum corneum is the outermost layer
of
the epidermis.
 It consisting of dead cells (corneocytes).
 The stratum corneum is the rate limiting
barrier
that restricts the inward & outward
movement of
chemical substances.
 These corneocytes are embedded in a lipid

13.  The stratum corneum functions to form a barrier
to protect underlying tissue from infection,
dehydration, chemicals and mechanical stress.
 stratum corneum contain a dense network of
keratin, a protein that helps keep the skin
hydrated by preventing water evaporation.
 These cells can also absorb water, further
aiding in hydration.
 This layer is responsible for the "spring back" or
stretchy properties of skin.

14.  The stratum corneum exhibit regional difference
in thickness over the body.
 In the over most of the body it is about 10μm
thick.
 When dry, increasing to about 40μm to 50μm.
 It is thick on the palm of the hand & soles of the
feet in an adult.

15. DERMIS
 The dermis is the layer of skin beneath the
epidermis that consists of epithelial tissue and
cushions the body from stress and strain.
 The dermis is tightly connected to the epidermis
by a basement membrane.
 It also harbors many nerve endings that provide
the sense of touch and heat.

16.  It contains the hair follicles, sweat glands,
sebaceous glands, apocrine glands, lymphatic
vessels and blood vessels.
 The blood vessels in the dermis provide
nourishment and waste removal from its own
cells as well as from the Stratum basale of the
epidermis.
 The dermis is structurally divided into two
areas: a superficial area adjacent to the
epidermis, called the papillary region, and a
deep thicker area known as the reticular region.

18. MECHANISMS & FACTORS INFLUENCING
DERMAL PENETRATION OF DRUG
Absorption of substances through the skin
depends on a number of factors:
 Concentration
 Molecular Weight of the molecule
 Duration of contact
 Solubility of medication
 Physical condition of the skin
 Part of the body exposed including the
amount of hair on the skin.

19.  small amounts of chemicals may enter the
body rapidly through the glands or hair
follicles, they are primarily absorbed
through the epidermis.
 The stratum corneum is the outermost layer
of the epidermis and the rate-limiting barrier
in absorption of an agent.
 Once a substance passes through stratum
corneum, then its no significant further
hindrance to penetration of the remaining
epidermal layer & corium.

20.  The stratum corneum is primarily composed
of lipophilic cholesterol, cholesterol esters
and ceramides (fatty acids).
 Thus lipid-soluble chemicals make it
through the layer and into the circulation
faster, however nearly all molecules
penetrate it to some minimal degree.
 Also, penetration depending upon effective
blood flow, interstitial fluid movement.

21. BIOAVABILITY OF DRUG
For bioavailability there are two factors are
most important
1. Choice of vehicle (Base).
2. Maximizing movement (partitioning) of drug
from vehicle to stratum corneum.

22. CHOICE OF VEHICLE
 Greases & oils are the most occlusive
vehicles those induce the greatest hydration
through sweat & accumulation at the skin-
vehicle interface.
 Vehicle such as, humectants, they have high
affinity for water.
 Such vehicle dehydrate the stratum
corneum & decrease the penetration.

23.  Powders increases the rate of evaporation
of water.
 paraffin bases suppress transepidermal
water diffusion.
 Skin secretions are more readily miscible
with emulsion bases than with greasy
bases.
 Those miscible drugs is more rapidly
release to the skin.
 So, that type of the bases required small

24. MAXIMIZING MOVEMENT (PARTITIONING) OF
DRUG FROM VEHICLE TO STRATUM CORNEUM.
 The medicament is favored vehicles which have
low soluble.
 On that reason, they loosely combine with
vehicle.
 Therefore, the rate of release from such drug
vehicle combination is fast.

25.  Surface active agents appears to increase
permeability of the skin to water by altering the
physical state of water in the skin.
 Anionics surfactant have good ability to
penetration than cationics & non-ionics.
 Soaps of different fatty acids have greater
penetration for salts of fatty acids having a
carbon length of 10 or less.

26.  Drugs with molecular weight of 100 to 800 &
adequate lipid & aqueous solubility can
permeate skin.
 The ideal molecular weight of drug for
transdermal drug delivery is to be 400 or less.

27. PREPARATION OF SEMISOLIDS
DOSAGE FORMS
INGREDIENTS USED IN PREPARATION:
 Bases
 Preservative
 Humectants
 Antioxidants
 Emulsifier
 Gelling agent
 Permeation enhancer
 Buffers

28. BASES
 It is one of the most important ingredient
used in formulation of semisolid dosage
form. Ointment bases do not merely act as
the carriers of the medicaments, but they
also control the extent of absorption of
medicaments incorporated in them.

29. IDEAL PROPERTIES OF A BASE
They should be:
 Inert, non-irritating and non-sensitizing.
 Compatible with skin pH and the drug.
 Good solvent and/or emulsifying agent.
 Emollient, protective, non-greasy and easily
removable.
 Release medicament readily at the site of
application.
 Pharmaceutically elegant and possess good
stability.

30. ANTIOXIDANTS
Oxygen is a highly reactive atom that is
capable of becoming part of potentially
damaging molecules commonly called “free
radicals.”
Free radicals are capable of attacking the
healthy cells of the body, causing them to
lose their structure and function. To
prevent this an antioxidants are added.
E.g. Butylated hydroxy anisole, Butylated
hydroxy toluene

31. PERMEATION ENHANCERS
 Skin can act as a barrier. With the
introduction of various penetration
enhancers, penetration of the drug through
the skin can be improved.
 E.g. Oleic Acid

32. EMULSIFIER
 An emulsifier (emulgent) is a substance that
stabilizes an emulsion by increasing its
kinetic stability.
- Must reduce surface tension for proper
emulsification.
- Prevents coalescence.
- Ability to increase the viscosity at low
concentration.

33. HUMECTANT
A humectant is a hygroscopic substance,
Humectants are used to :
 increase the solubility of the active
ingredient
 to elevate its skin penetration.
 elevate the hydration of the skin.

34. BUFFERS
Buffers are added for various purpose such as
:
- Compatibility with skin.
- Drug solubility.
- Drug stability.
- E.g. sodium acetate, sodium citrate,
potassium metaphosphate.

35. OINTMENTS
 Ointments are homogenous, translucent,
viscous semi-solid preparations, most
commonly a greasy, thick oil (oil 80% - water
20%) intended for external application to the
skin or mucous membrane.
 Drug ingredients can be dissolved, emulsified
or suspended in the ointment base.

36. OINTMENTS BASES
 Oleaginous bases or Hydrocarbon bases
 Absorption bases
 Water-miscible bases/removable
bases/Emulsifying bases
 Water-soluble bases

37. OLEAGINOUS BASES
(HYDROCARBON BASES)
 Oleaginous bases are non-aqueous
formulations which provides emollient &
protective properties.
 It is difficult to remove hydrocarbon bases from
skin due to their oily nature.
 E.g. Hard Paraffin, White or Yellow soft
paraffin, Liquid paraffin, Mineral oil etc..

38. ABSORPTION BASES
 In the absorption bases contains small amt. of
water & they provide relatively less emollient
properties than hydrocarbon bases.
 These bases are generally anhydrous
substances which have the property of
absorbing considerable quty. of water but still
retaining their ointment like consistency.
 They have 2 types : 1. Non-emulsified bases
2. Water in oil emulsion
bases

39.  Non-emulsified bases:
Those bases absorb water &
aqueous solution producing W/O emulsion.
e.g. Wool fat, Wool alcohol, Bees Wax etc..
 Water in oil emulsion bases:
Those bases have the
capability of absorbing more water & have the
properties of non- emulsified bases.
e.g. Hydrous wool fat (Lanolin)

40. WATER-MISCIBLE BASES/REMOVABLE
BASES/ EMULSIFYING BASES
 These are anhydrous, hydrophilic, absorbs
water with low thermal conductivity.
 It is easy to remove these bases from the skin
due to their hydrophilic nature. These are used
to form oil in water emulsion for topical
applications.
 They have the same properties as the
absorption bases.
 They are used as emollients, cleansing creams,
vehicle for solid, liquid drugs.
 e.g. cold cream type, hydrous lanoline, rose
water ointment etc.

41. WATER SOLUBLE BASES
 In that bases does not contain oily substances
& are called greaseless bases & completely
soluble in water.
 Those are prepared using mixtures of different
molecular weights of polyethylene glycol
(Macrogols).
 PEG are mixture of polycondensation product
of ethylene oxide & water.
 Lower M.W of this polymers (200,400 &
600g/mol) are liquids & the average M.W
increases of this polymers changes from liq. To
a waxy solid but not greater than 1000g/mol.

42. CLASSIFICATION OF OINTMENTS
 On the basis of penetration
 On the basis of therapeutic use

43. ON THE BASIS OF PENETRATION
A- Epidermic ointments
 These ointments are intended to produce their
action on the surface of the skin and produce
local effect,they are not absorbed.
 They acts as protectives, antiseptics and
parasiticides.
B- Endodermic ointments
 These ointments are intended to release the
medicaments that penetrate into the skin. They
are partially absorbed and acts as emollients,
stimulants and local irritants.
C- Diadermic ointments
 These ointments are intended to release the
medicaments that pass through the skin and
produce systemic effects.

44. ON THE BASIS OF THERAPEUTIC USE
 Antibiotic Ointments e.g bacitracin
 Antifungal Ointments e.g Benzoic acid
 Anti-inflammatory Ointments e.g fluocinolone
acetonide
 Antipruritic Ointments e.g benzocaine
 Counter-irritant Ointments e.g Methyl salicylate
 Antidandruff Ointments e.g. Salicylic acid

45. METHOD OF PREPARATION
Both on a large and a small scale, ointments
are prepared by three general methods:
 Incorporation Method / Trituration Method
 Fusion Method
 Chemical Reaction
The method for a particular preparation
depends primarily upon the nature of the
ingredients

46. INCORPORATION METHOD /
TRITURATION METHOD
 Powders pass out from mesh no. 250 or 180
or 125.
 Then apply levigation process with small
amt. of base.
 Then add remaining quty. of base.
 Finally add liquid ingredients & mix well.
 E.g Whitfield Ointment

48. FUSION METHOD
 When an ointment base contains a number of
solid ingredients such as white bees wax, cetyl
alcohol, stearyl alcohol, hard paraffin etc.
 By the fusion method, all or some of the
components of an ointment are combined by
being melted together and cooled with
constant stirring until congealed.
 Naturally, heat-labile substances and any
volatile components are added last when the
temperature of the mixture is low enough not to
cause decomposition of volatilization of the
components.

50. CHEMICAL REACTION
 Ointment containing free iodine
 Ointment containing combined iodine

51. OINTMENT CONTAINING FREE IODINE
 Iodine is slightly soluble in most fats & oil but
very readily soluble in conc. Aq.solution of
potassium iodide due to formation of molecular
complex.
 E.g. Strong iodine ointment B.Vet.C is used to
treat ringworm in cattle. At one time this type
ointment used on humans for counter-irritants
but they were not popular bec. they remain
stain on skin a deep red colour.

52. OINTMENT CONTAINING COMBINED IODINE
 Fixed oils & many vegetable & animal fats
absorb iodine which combines with the double
bounds of the unsaturated constitutes.
Oleic acid + iodine = di-iodo stearic acid
 E.g. Non-staining Iodine Ointment BPC

53. PASTE
 Pastes are homogeneous semisolid dosage
form contains high conc. Of insoluble powder
substance ( not less than 20%) dispersed in
the suitable base.
 The paste are usually less greasy, more
absorptive & stiffer than ointments.
 They have good adhesion on skin.

54. FUSION METHOD
 Powder ingredients pass through under
mesh no.180
 Melt all bases & wax with conti. Stirring.
 Then add powder form ingredient.
 And again continuous or constant stirring
until cool.
 E.g zinc & coal tar paste.
 Use : treatment for eczema

55. FUSION & TRITURATION METHOD
 Pass the powders through mesh no. 180.
 Then melt the base
 Take powder in mortar & triturated with
melted base.
 Triturate until become cool.
 E.g compound zinc paste BP
 Use: treatment for eczema & also act as a
sun protecting.

56. CREAMS
 Creams are defines as “a semisolid dosage
form containing one or more drug substances
dissolved or dispersed in a suitable base”
 Creams are prepared W/O or O/W it depends
upon the nature of solids present in the internal
phase.
 It is used as a protectant, for therapeutic
purpose & for cosmetic purpose.

57. TYPES
 Oil in Water (O/W) Cream
 Water in Oil (W/O) Cream
 COSMETIC CREAMS
 MEDICATED CREAMS

58. OIL IN WATER (O/W) CREAM
 oil-in-water (O/W) creams which are composed of small
droplets of oil dispersed in a continuous phase.
 More comfortable and cosmetically acceptable as they
are less greasy and more easily washed off using water.
 Emulsifying agents of natural origins( bees wax, wool
alcohols, wool fat).
 Emollient and creamy, white or translucent and stiff.
 E.g. Vanishing Cream

59. WATER IN OIL (W/O) CREAM
 water-in-oil (W/O) creams which are composed of small
droplets of water dispersed in a continuous oily phase.
 More difficult to handle but many drugs which are
incorporated into creams are hydrophobic and will be
released more readily from a W/O cream than an O/W
cream.
 More moisturizing as they provide an oily barrier which
reduces water loss from the stratum corneum, the
outermost layer of the skin.
 e.g. Cold Cream

60. COSMETIC CREAMS
 All purpose cream, baby cream, barrier
cream, bleaching cream, cleansing cream,
cold cream, hair cream, hand cream,
vanishing cream.

61. MEDICATED CREAMS
 Medicated creams are contains active
pharmaceutical ingredients.
 e.g. Cetrimide cream used as antiseptic.
Zinc oxide cream used as astringent.

62. FORMULATION METHOD
 Preparation of the oil phase: Flake/powder ingredients,
sometimes dry blended in advance, are dispersed into
mineral oil or silicone oil. Heating may be required to melt
some ingredients.
 Hydration of aqueous phase ingredients: Emulsifiers,
thickeners and stabilizers are dispersed into water in a
separate vessel. Heating may be required to accelerate
hydration.
 Forming the Emulsion: The two phases are blended under
vigorous agitation to form the emulsion.
 Dispersion of the Active Ingredient: The active ingredient
often makes up only a small proportion of the formulation;
this must be efficiently dispersed to maximize yield and
product effectiveness.

63. GELS
 Gels are semisolid dosage form.
 In that dispersion of small or large molecules in an aqueous
liquid vehicle.
 They produce jelly like consistency by the addition of a
gelling agent.
 Gels are formed by using synthetic polymers such as
carbomer 934 & cellulose such as hydroxypropylcellulose
& hdroxypropylmethylcellulose.
 Tragacanth, pectin, agar natural gums are used in the
formulation of gels.

64.  As per NF, six polymers are used for gel
formulation. Those are followings,
 Carbomers 910
 Carbomer 934
 Carbomer 934P
 Carbomer 940
 Carbomer 941
And
 Carbomer 1342
 Carbomer 940 produce highest viscosity betw.
40,000 & 60,000 centipoises in 0.5% aq. Solution.

65. CLASSIFICATION OF GELS
 HYDROGELS
 XEROGELS
 ORGANOGELS

66. HYDROGELS
 A hydrogel is a network of polymer chains that are
hydrophilic, sometimes found as a colloidal gel in
which water is the dispersion medium.
 Hydrogels are highly absorbent(they can contain
over 90% water) natural or synthetic polymeric
networks.
 Hydrogels also possess a degree of flexibility very
similar to natural tissue, due to their significant
water content.
 Common ingredients include polyvinyl alcohol,
sodium polyacrylate, acrylate polymers and

67. USES:
 As environment sensitivity detector.
 Sustained release DDS.
 Contact lenses.
 ECG medical electrode.
 Glue

68. XEROGELS
 Open network formed by the removal of all
swelling agents from a gel.
 Xerogels usually retain high porosity (15–50%)
and enormous surface area (150–900 m2/g),
along with very small pore size (1–10 nm).
 When solvent removal occurs under
supercritical conditions, the network does not
shrink and a highly porous, low-density
material known as an aerogel is produced.

69. ORGANOGELS
 An organogel is a non-crystalline, non-glassy
thermo reversible (thermoplastic) solid material
composed of a liquid organic phase entrapped
in a three-dimensionally cross-linked network.
 The liquid can be, for example, an organic
solvent, mineral oil, or vegetable oil.
 These systems are based on self-assembly of
the structuring molecules.

70. METHOD OF FORMULATION
There are 3 methods:
 Fusion Method
 Cold Method
 Dispersion Method

71. FUSION METHOD
 In this method various waxy materials
employed as gellant in non polar media.
 Drug was added when waxy materials
melted by fusion.
 stirred slowly until uniform gel formed.

72. COLD METHOD
 Water was cooled to 4-100c and placed it in
mixing container.
 Gelling agent was slowly added and
agitating until solution is complete.
 Maintained temperature below 100c .
 Drug was added in solution form slowly with
gentle mixing.
 Immediately transfer to container & allow to
warm to R.T where upon liquid becomes
clear gel.

73. DISPERSION METHOD
 Gelling agent was dispersed in water with
stirring at 1200 rpm for 30 min .
 Drug was dissolved in non-aqueous solvent
with preservative.
 This solution was added in above gel with
continuous stirring.

74. EVALUATION TESTS FOR
SEMI-SOLID DOSAGE FORM
 Content uniformity of drug
 Penetration
 Rate of release of medicament
 Absorption of medicament into blood stream
 Irritant effect

75. PENETRATION
 A weighed qty.of ointment is rubbed over skin
for given period of time.
 Collect unabsorbed ointment from the skin &
weighed.
 The difference in weights represents the
amount absorbed.

76. RATE OF RELEASE OF MEDICAMENT
 This test performed on the surface of nutrient
agar.
 If the medicament is bactericidal the agar plate
is previously seeded with suitable organism like
s.aureus.
 After a suitable period of incubation, the zone of
inhibition is measured & correlated with the rate
of release.