1

Semisolid Dosage Forms (4 CU).

(Transdermal drug delivery system)
- Definitions and types of semi-solid
-Anatomy of the skin.
- Mechanisms of drug penetration through skin.
- Semisolid bases and their selection.
-General formulation of semisolids (ointment and gel),
manufacturing procedure, evaluation and packaging.
-Transdermal therapeutic systems (TTS); types and
preparation.
-Novel mechanisms and devices to enhance skin delivery; Penetration
enhancers, types and mechanism of action; Liposomes and other vesicles;
Electrically assisted transdermal delivery system (iontophoresis and
electroporation). Sonophoresis, high velocity particles and stratum
corneum abletion.
2
Solid dosage forms
a. Tablets (8 cu)
-Introduction to unit solid dosage forms; tablets
Tablet exciepients
Formulation of tablets; tablet machines (single
punch and rotary press machine).
Granulation techniques; wet and dry
granulation.
-Tablets prepared by direct compression.
a. Tablets (cont.)
Tablet coating; Type of tablet coating (sugar, film
and compression coat), methods of coating,
functional coat.
Tablet standers.
Problems associated with tablet manufacture
(e.g Lamination, Capping, sticking, picking,)
Quality control tests for tablets (weight variation,
disintegration, dissolution, thickness and
diameter, friability).
3
B. Molded solid dosage forms ;suppositories
(4 cu) .
Anatomy of the rectum and vagina.
Factors affecting drug release from suppositories;
physiological and physicochemical considerations.
Ideal requirements, bases, manufacturing
procedure, packaging and evaluation.
Formulation
Quality control tests
Packaging and storage
C. Capsules (2CU).
- Advantage and disadvantages of capsule dosage form,
material for production of hard gelatin capsules, size of
capsules.
- Methods of capsule production, soft gelatin capsule shell
and capsule content, importance of base absorption and
minim/gm factors in soft capsules.
- Quality control, stability testing and storage of capsule
dosage forms.
Microcapsulation (2CU).
-Types of microcapsules; importance of
microencapsulation in pharmacy.
-Microcapsulation by phase seperation, co-acervation
multiorifice, spray drying, spray congealing, polymerization,
complex emulsion, air suspension technique, coating pan
and other techniques.
4
D. Micromeritics (2CU).
Particle size and size distribution.
Methods for determining particle size.
Particle shape and surface area.
Porosity.
Densities of particles.
Methods used for determination of powder
density, with practical examples
Flow properties.
Compaction.
Semisolid Dosage Forms
5
objectives
To introduce the student to the structure,
functions and topical treatment of human
skin
To deal with the principles of membrane
diffusion, skin transport and properties
affecting transdermal delivery
To identify dermatological vehicles and
methods of preparation
To review the philosophy of transdermal
patches
SEMISOLID PREPRATIONS
DEFINITION:
Semisolid dosage forms are products of
semisolid consistency and applied to skin
or mucous membranes for therapeutic or
protective action or cosmetic function.
6
IDEAL PROPERTIES OF SEMISOLID
DOSAGE FORMS
1- PHYSICAL PROPERTIES:
a)Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non staining
f) Non hygroscopic
IDEAL PROPERTIES OF SEMISOLID
DOSAGE FORMS
2-PHYSIOLOGICAL PROPERTIES:
a) Non irritating
b) Do not alter membrane / skin functioning
c) Miscible with skin secretion
d) Have low sensitization effect
3-APPLICATION PROPERTIES:
a) Easily applicable with efficient drug release
b) High aqueous washability
7
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
1-OINTMENTS:
They are soft hydrocarbon based semisolid
preparations, composed of fluid hydrocarbon
meshed in a matrix of higher melting solid
hydrocarbon, e.g. pertrolatum.
Since they are of greasy nature so they stain
cloths, are generally poor solvent for most drugs,
and usually decrease the drug delivery
capabilities of the system.
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
2-CREAMS:
They are viscous semisolid emulsion system
with opaque appearance compared with the
translucent ointments. Consistency and
rheological characters depend on weather the
cream is w/o or o/w.
Properly designed O/W creams are elegant drug
delivery system, pleasing in both appearance
and feel after application.
O/W creams are non greasy and are rinsable.
They are good for most topical purposes.
8
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
3-PASTES:
Pastes are basically ointments into which a high
percentage of insoluble solid has been added. The
extraordinary amount of particulate matter stiffens the
system.
Pastes are less penetrating than ointment .
Paste make particularly good protective barrier when
placed on the skin for, in addition to forming an unbroken
film, the solid they contain can absorb and thereby
neutralize certain noxious chemicals before they ever
reach the skin .
Like ointments, paste forms an unbroken relatively water
impermeable film. Unlike ointments, the film is opaque
and therefore, an effective sun block accordingly.
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
4-GELS (JELLIES):
Gels are semisolid coherent system in
which a liquid phase is constrained
within a polymeric matrix (consisting of
natural or synthetic gum) having a high
degree of physical or chemical cross-
linking .
Gels are transparent or translucent
non-greasy semisolid gels .
Some are as transparent as water
itself, an aesthetically pleasing state,
other are turbid, as the polymer is
present in colloidal aggregates that
disperse light .
They are used for medication or
lubrication.
9
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
5- POULTICES:
It is soft, viscous, pasty preparation for
external use. Poultice must retain heat for a
considerable time because they are intended
to supply warmth to inflamed parts of body.
Poultices act by increasing blood flow,
relaxing tense muscles, soothing inflamed
tissues, or drawing toxins from an infected
area. Thus, they can be used to relieve the
pain and inflammation associated with
abscesses; (e.g. Kaolin poultice B.P.C.)
TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS
6-SEMISOLID FOAMS:
Foams are system in which air or some
other gas is emulsified in liquid phase to
the point of stiffening .
E.g. shaving creams, whipped creams,
aerosolized shaving creams .
10
Conventional topical vehicles, such as
ointments, creams or gels, predominantly exert
their effect by releasing the drug onto the skin
surface, and the drug molecules then diffuse
through the skin layers. The extent and duration
of diffusion depends on the (1) physicochemical
properties of the drug, (2) the type of base and
(3) skin condition.
In general, the modification of drug absorption
kinetics by these vehicles is the result of their
ability to provide increased hydration by
occlusion or some other mechanism.
Functions
Structure
11
Structure of the skin: its barrier
properties
The skin is the largest organ of the body and acts as a
protective barrier with sensory and immunological
functions.
Human skin is, on average, 0.5 mm thick (ranging from
0.05 mm in eye lid to 2 mm).
Classification of skin based on the epidermis alone
especially the surface layer (stratum corneum):
- thick: palms of hand, soles of feet
- thin: rest of the body
Although the skin is one of the major sites for non-
invasive delivery of therapeutic agents into the body, this
task can be relatively challenging owing to the
impermeability of the skin.
12
Skin Structure
The skin consists of three major layers:
- Epidermis
- Dermis
- Subcutaneous tissues
Skin Structure
Schematic cross section of the skin
13
Skin Structure
Skin Structure
1. Epidermal layer:
- Stratum Corneum (SC) or horny layer
- Viable epidermis
14
Stratum corneum (SC) = horny layer
The stratum corneum (10-20-m) is the
outermost horny layer of skin, comprising
about 15-20 rows of flat, partially
desiccated, dead, keratinized epidermal
cells (corneocytes), which are constantly
shed and renewed.
Its organization can be described by the
brick and mortar model, in which extra
cellular lipid accounts for ~10% of the dry
weight and arranged in a bilayer format and
form so called lipid channels
It represent the main barrier function of the
skin.
Stratum corneum (cont.)
Because of its highly organized
structure, the SC is the major
permeability barrier to external
materials, and is regarded as the
rate-limiting factor in the
penetration of therapeutic agents
through the skin.
The ability of various agents to
interact with the intercellular lipid
therefore dictates the degree to
which it can penetrate.
15
Viable epidermis
The viable epidermis consists of multiple layers of
keratinocytes at various stages of differentiation.
Does not contain blood vessel but contain nerve ending
for touch and pain.
The role of the viable epidermis in skin barrier function is
mainly related to the intercellular lipid channels.
Depending on their solubility, drugs can partition from
layer to layer after diffusing through the SC.
contains metabolic enzymes
Cell types:
Keratinocytes: produce keratine
Melanocytes: produce melanine
Langrhans cells: immune cells, defense mechanism
Layers of epidermis
16
2. Dermis & Subcutaneous Tissue
Dermis = layer beneath epidermis (3-5 mm)
Composed of collagen fibril and elastic tissue providing elasticity
and flexibility.
Connective tissue
Nerves
Blood vessels
Lymphatics
- Supports and nourishes skin
- Minimal barrier to drug penetration
Subcutaneous tissue = layer beneath dermis
Connective tissue
Fat
- Insulate the body, protect against physical shock and source of
energy supply
- Absent in eyelid
Skin appendages
There are three main appendages:
A. Hair follicles; found all over the body except load-
bearing areas (soles of feet and palms of hands) and lips.
B. Sebaceous glands; secret sebum (mix. of fatty acids
and waxes) which help to lubricate skin surface and
maintain surface pH of around 5.
Sweat gland;
- Eccrine glands at density of 100-200 per cm
2
-Apocrine glands less in number and limited to certain area
of the skin e.g. armpit, nipples and per anal region.
17
Preparations for dermal use
Preparations for transdermal use
(percutaneous absorption)
18
The skin
The most extensive and readily accessible organ
Covers a surface area of approximately 2 m
2
Receives about one-third of the blood circulation.
Composed of three tissue layers:
Epidermis
Dermis
Subcutaneous fat tissue or hypodermis
Skin structure
19
Dermal and transdermal drug
delivery
Semisolid dosage forms for dermatological drug
therapy are intended to produce desired
therapeutic action at specific sites in the
epidermal tissue .
A drugs ability to penetrate the skins epidermis,
dermis, and subcutaneous fat layers will lead to
transdermal (percutaneous) drug delivery giving
rise to systemic action .
Therefore, the extent the drug can travel through
the different skin layers determine the delivery
system.
- Avoiding hepatic first pass effect
- Continuous drug delivery
- Fewer side effect
- Therapy can be terminated at any time
- Improved patient compliances
Disadvantages:
- Cosmetically non-appealing
- May display erratic (irregular) absorption
Why Transdermal drug delivery?
20
Possible Routes of Skin Penetration
Drugs can penetrate skin barrier by three routes:
-Transcellular (across cells)
-Intercellular (between cells)
-Transappendageal (via hair follicles, sweat
and sebum glands)
Percutaneous drug absorption results from direct
penetration through the stratum corneum, followed
by passing through the epidermal tissues and into
the dermis.
Pathways of drug penetration
through skin
Simplified diagrams showing routes of drug penetration.
(a) Macroroutes of drug penetration (1) across the continuous stratum
corneum; (2) through the hair follicles with their associated sebaceous
glands or (3) via the sweat duct.
(b) Representation of the stratum corneum membrane, illustrating two
possible microroutes for permeation. (1) Intercellular (2) transcellular
21
Micro-routes of Penetration through SC
Penetration through SC could be:
- Trans-cellular pathway
- Inter-cellular pathway
Schematic of Skin Absorption
22
Process of transdermal permeation.
RATIONAL APPROACH TO TOPICAL
FORMULATION
In dermatology, we aim at five main target regions: skin
surface, horny layer, viable epidermis and upper dermis,
skin glands, and systemic circulation
(1) Surface treatment
We care for the skin surface mainly by using cosmetic
application, by forming a protective layer, or by attacking
bacteria and fungi.( sunscreens, barriers that hinder
moisture loss, antimicrobials and insect repellants)
(2) Stratum corneum treatment
The main therapies aimed at the horny layer improve
emolliency by raising water content or stimulating
sloughing (keratosis, Exfolients such as salicylic acid).
23
RATIONAL APPROACH TO TOPICAL
FORMULATION
(3)Skin appendage treatment
Antiperspirants (aluminium) reduce hyperhydrosis of the
sweat glands. Depilatory,Topical antibiotics, Antifungals,
Exfolients for acne treatment.
(4) Viable epidermis and dermis treatment
We can treat many diseases provided that the
preparation efficiently delivers drug to the receptor (anti-
inflammatory, anesthetic, antihistamine).
RATIONAL APPROACH TO TOPICAL
FORMULATION
(5) Systemic treatment via percutaneous absorption
In recent years considerable scientific work has led the
route being used to treat several conditions by means of
transdermal patches (e.g. motion sickness (hyoscine),
angina (nitroglycerin).
24
The fraction of the drug that penetrate the
skin via any route depends on:
The physicochemical nature of the drug,
specially its size, solubility and partition
coefficient
The site and condition of the skin
The formulation
How vehicle component temporarily change
the properties of the stratum corneum
25
( )
2 1
C C
h
DAK
dt
dQ
p

|
|
.
|

\
|
=
dQ/dt - rate of diffusion D - diffusion coefficient
A - surface area of membrane K
p
- partition coefficient
h - membrane thickness
C
1
- C
2
= concentration difference for solute
Generally, C
1
>>C
2
- Basic principle of diffusion through membranes
Ficks Law of Diffusion
Skin Permeability
Skin Permeability
Since D, Kp, and h are constant for a given
drug/membrane; and given that C1>>C2:
1
PC
dt
dQ
=
Where P - permeability constant
26
Ideal molecular properties for drug
penetration
A low molecular weight (generally less than 500
Daltons)
An adequate solubility in oil and water
A balanced partition coefficient
A low melting point
Potent drug (maximum 50 mg/day)
Factors Affecting Transdermal
Delivery
Physiological factors
Physicochemical factors
27
PHYSIOLOGICAL FACTORS
1. Skin condition
Intact skin is a barrier
Damaged skin more permeable
Diseased skin usually more permeable
2. Skin age
- babies and children greater area/weight than
adult- absorb more drug e.g. steriod
- premature infants- no stratum corneum
- e.g. the use of topical caffeine for breathing
difficulties
3. Regional skin site
- wide variation e.g face to foot
Effect of Nitroglycerin on Systolic Blood Pressure When
Adminisitered Percutaneously at Different Sites
-15
-10
-5
0
5
0 50 100 150 200
C
h
a
n
g
e

i
n

M
e
a
n

S
B
P

(
m
m
H
g
)
Forehead
Chest
Ankle
PHYSIOLOGICAL FACTORS
28
PHYSICOCHEMICAL FACTORS
1. Skin hydration
- important as it usually promotes permeation
- principle factor
- Rank order:
- occlusive film
- ointment
- creams
PHYSICOCHEMICAL FACTORS
2. Temperature and pH
- diffusion depends on temperature (direct
relationship).
- pH- Partition theory applies i.e nonionic
molecules is more permeable than ionic
- Stratum corneum, pH = 4.5 6
- How pH affect drug penetration???
29
PHYSICOCHEMICAL FACTORS
3. Drug concentration
- obeys Ficks law
dQ/dt = KDC/h
4. Partition coefficient
- also obeys Ficks law
- moderate value (Why????)
5. Diffusion coefficient
6. Molecular size
- absorption should be inversely proportion to
size (M.Wt.)
Topical dosage forms
Ointments
Creams
Pastes
Gels/jellies
Solution
Plasters
Aerosols
Powders
30
FORMULATION OF SEMISOLID
DOSAGE FORMS
1- INGREDIENTS USED IN PREPARATION OF
SEMISOLIDS:
Ingredients used for formulating semisolids include : -
-Active pharamaceutical ingredient API ,
-Bases,
-Antimicrobial preservative ,
-Humectants ,
-Fragrances,
-Emulsifier
-Gelling agent,
-Permeation enhancer
INGREDIENTS USED IN PREPARATION OF SEMISOLIDS
1.1. ACTIVE PHARMACEUTICAL INGREDIENTS, API
Disease treated API
Warts (Keratolytic) Salicylic acid
Acne Sulphur, resorcinol
Antipruritic Benzocain, menthol
Emollient lanolin
Anti-inflammatory corticosteroid
Antifungal Benzoic acid
31
32
Ointments
An ointment is a viscous semisolid preparation used
topically on a variety of body surfaces. These include
the skin and the mucus membranes of the eye (an eye
ointment), vagina, anus, and nose.
An ointment may or may not be medicated.
Typically used as:
Emollients to make skin more pliable
Protective barriers
Vehicles in which to incorporate medication
Ointment
1.2. Ointment Bases
Semisolid bases do not only act as the carriers of the
medicaments, but they also control the extent of absorption of
medicaments incorporated therin .
An ointment base should be compatible with skin, stable,
smooth, non-irritating, non-sensitizing, inert, capable of
absorbing water or other liquid preparations, and of releasing
the incorporated medicament, readily .
A base for ophthalmic semisolids must be non-irritating to the
eye, and It should also be sterilizable conveniently .
33
INGREDIENTS USED IN PREPARATION OF SEMISOLIDS (CONT(.
ointment bases
Appropriate Selection of Ointment Base:
Selection of ointment base depends on the following :
1-Desired release rate of the drug substance from the
ointment base .
2-Rate and extent of topical or percutaneous drug
absorption .
3-Desirability of occlusion of moisture from skin .
4-Stability of the drug in the ointment base .
5-Effect of drug on the consistency of base .
6-Easy removal of base on washing .
7-Characteristic of the surface to which it is applied .
INGREDIENTS USED IN PREPARATION OF
SEMISOLIDS (CONT(.
ointment bases
Ointment bases may be classified in several
ways but the following classification based on
composition is generally used which are as
follow ,
A) Oleaginous (hydrocarbon) bases .
B) Absorption bases .
C) Emulsion bases .
D) Water soluble bases .
34
A) Oleaginous )hydrocarbon) bases:
This is a purified mix of liquid, semi-solid or
solid hydrocarbons from petroleum
Most of the early ointment bases used to be
exclusively oleaginous in nature but nowadays
the materials obtained from plant, animal, as
well as synthetic origin are employed as
oleaginous ointment bases.
Combinations of these materials can produce a
wide range of melting points and viscosities .
Ointment bases
A) Oleaginous (hydrocarbon) bases - :
These bases are:
- Immiscible with water (they are difficult to wash off)
- Not absorbed by the skin, remain on the skin for
prolonged period of time without drying out
- Absorb very little water from formulation or from
skin exudates.
- Inhibit water loss from the skin by forming a water
proof film (OCCLUSIVE DRESSING).
- Improving hydration, may encourage penetration of
the medication through skin.
Examples: Vaseline, hard paraffin, liquid paraffin,
white ointment
Uses: protectants, emollient, and vehicle for solid
drugs
35
Occlusive and skin hydration
B) Absorption (Emulsifiable) Bases:
They are called as emulsifiable bases because
they initially contain no water but are capable of
taking it up to yield W/O and O/W emulsions .
Absorption bases are mostly W/O type
emulsions and have capacity to absorb
considerable quantities of water or aqueous
solution without marked changes in consistency .
36
Ointment bases
Absorption bases are:
- less occlusive than the hydrocarbon bases.
- Incorporation of aqueous solution is possible.
- easier to spread.
- good emollients
- They hydrate the stratum corneum.
- Not easily removed from the skin with water
washing (external phase is oleaginous)
- Uses: protectants, emollient, and vehicle for
aqueous solutions and solid drugs
Ointment bases (cont.)
Absorption base (cont.)
Lanolin, anhydrous lanolin, wool fat, wool
wax (obtained from wool of sheep)
This is a type of wax- like that can absorb about 50%
of its weight of water and is used in ointments in
which the proportion of aqueous fluid is too large for
incorporation into a hydrocarbon base.
- Wool fat is a major constituent of Simple Ointment
BP
Other examples: hydrous lanolin, bees wax and
cholesterol (they are added to some ointment bases to
increase their water-absorbing power)
37
Ointment bases (cont.)
(C) Emulsion Bases:
They are either w/o or o/w
Hydrophilic Ointment USP
Cold cream: W/O emulsions, emollient, cleansing, not
water washable, non occlusive, shiny appearance, not
need glycerin.
Vanishing cream: O/W emulsion contains large % of
water and humectant. An excess of stearic acid in the
formula helps to form a thin film when the water
evaporates.
Ointment bases (cont.)
Properties of Emulsion bases:
Water-washable, easier to remove
Non/less greasy
Can be diluted with water
Non/less occlusive
Better cosmetic appearance
Better compliance; Patients prefer cream to an
ointment because the cream spreads more readily,
less greasy, evaporating water soothes the inflamed
tissue.
Uses: Cleansing creams, emollients and vehicle for
solid and liquid drugs.
38
INGREDIENTS USED IN PREPARATION OF SEMISOLIDS (CONT).
Ointment bases
D) Water Soluble Bases:
Water soluble and water washable
greaseless,
Because they soften with the addition of water,
large amounts of aqueous solutions are not
effectively incorporated into these bases.
Uses: drug vehicle
Ointment bases (cont.)
D) Water Soluble Bases
The water-soluble bases have the advantages of
being:
- Water soluble and washable
- Non-greasy, non-staining
- Non/less occlusive
- Lipid free
- Relatively inert
- Does not support mold growth
- Little hydrolysis, stable
-Disadvantages: May dehydrate skin and hinder
percutaneous absorption.
39
The macrogols (carbowax) are
mixtures of poly-condensation
products of ethylene oxide and water
and they are described by their
average molecular weights (viscous
liquids to waxy solids).
Different grades of cabowaxes are
available which are designated by a
number roughly representing their
average molecular weights e.g.-
PEG 200, PEG 400, PEG1000,
PEG1540 and PEG 6000.
40
A general rule is that:
For wet lesions the patient should use
an aqueous dressing,
For dry skin a lipophilic base is best.
ANTIMICROBIAL PRESERVATIVES:
Some base, although, resist microbial attack but
because of their high water content, it require an
antimicrobial preservative. Commonly used
preservatives include Methyl hydroxybenzoate,
Propyl- hydroxybenzoate, Chlorocresol, Benzoic
acid, Phenyl mercuric nitrate, Benzalkonium
chloride, Chlorhexidine acetate, Benzyl alcohol
and Mercurial .
41
INGREDIENTS USED IN PREPARATION OF
SEMISOLIDS (CONT.)
ANTIOXIDANTS:
Example of commonly used antioxidants include
Butylated hydroxy anisole, Butylated hydroxy toluene .
HUMECTANTS:

Example of commonly used humectants includes

Poly Ethylene Glycol, Glycerol or Sorbitol is added as
humectants .
FRAGRANCES:
Examples of widely use fragrances are Lavender oil,
Rose oil, Lemon oil, Almond oil .
METHODS OF PREPARATION
1- BY TRITURATION:(incorporation).
When base contain soft fats and oils or
medicament is insoluble or liquid, then this
method is use with spatula or mortar and pestle.
2- BY FUSION:
Used for large quantities or for ointments in
which waxes or solids of high melting points are
to be mixed with semisolid or oils. Constituents
are melted successively in decreasing order of
melting point.
3- BY OINTMENT MILLS:
It is used for large scale production where triple
roller mill is utilized which is faster then others .
42
Requirement for ointments
Microbial content: do not need to be
sterile, but must meet the FDA
requirement of the test for absence of
bacteria such as S. areus and P.
aeruginosa for dermatological
products.
Packaging, storage, labeling: (label
should include the type of base used)
Additional standards: viscosity, in
vitro release
CREAM
Semisolid preparations containing one or
more medicinal agents dissolved in either
an o/w or w/o emulsion or in another type
of water-washable base.
Typically of low viscosity, two phase
system (w/o or o/w)
Appears creamy white due to the
scattering of light.
Traditionally, it is the w/o cold cream
Currently and most commonly, it is the o/w
emulsion.
43
Creams as drug delivery systems
Good patient acceptance
Water evaporation concentrates drug on skin
surface
Examples;
Vanishing cream: o/w with high % of water and stearic
acid.
Cold cream: (an emulsion for softening and cleansing the
skin): w/o, white wax, spermaceti, almond oil, sodium
borate.
CREAM
EMULSIFIER:
Important in creams
Ideal properties of emulsifier includes:
a) Must reduce surface tension for proper
emulsification .
b) Prevents coalescence .
c) Effective at low concentration .
44
GELLING AGENTS:
Important for gel (jelly) semisolid preparations
These are organic hydrocolloids or hydrophilic
inorganic substances. They are Tragacanth,
Sodium Alginate, Pectin, Starch, Gelatin,
Cellulose Derivatives, Carbomer, and Poly Vinyl
Alcohol Clays .
There are numerous gelling agents varying in
gelling ability. Commonly used gelling agents
INGREDIENTS USED IN PREPARATION OF
SEMISOLIDS (CONT).
Material % Brookfield viscosity
CP
0

Carbomer 941resin NF
Carbomer 941resin NF
Carbomer 941resin NF
Carbomer 941resin NF
Sodium carboxymethyl cellulose
Guar gum
Methyl cellulose
Locust bean gum
Sodium alginate
0.15
0.25
0.50
1.00
1.50
1.50
2.00
2.50
2.50
2900
6300
44000
81000
5000
8040
5200
22800
10400
Table 4.4 : Gelling agents
(6)

- Commonly used Gelling agents
45
Some recent semi-solid preparation are
used via other routes of administration i.e.
other than topical route
46
Recent Advances in Semisolids
1. Ointment
Rectal Ointment: it is used for the
symptomatic relief against anal and peri-anal
pruritus, pain and inflammation associated with
hemorrhoids, anal fissure, fistulas and proctitis .
For intrarectal use, apply the ointment with the
help of special applicator .
Recent Advances in Semisolids
2. Creams
Creams containing microspheres:
Albumin microsphere containing vitamin A
can be administered by using creams
topically. These microspheres were able to
remain on the skin for a long period of
time, and as a consequence they were
able to prolong the release of vitamin A.
47
Recent Advances in Semisolids
3. Bioadhesive gels
Gel formulations with suitable rheological
and mucoadhesive properties increase the
contact time at the site of absorption
(nasal or ocular delivery(.
E.g. Chitosan bioadhesive gel was formulated for nasal
delivery of insulin .
Bioadhesive and pH sensitive
hydrogel
48
Recent Advances in Semisolids
4. Hydrogels
Usually made of hydrophilic polymers, which
under certain conditions and concentration,
jellify .
The polymer produces a coherent three-
dimensional net-like structure, which fixes the
liquid vehicle as the external phase. .
Intermolecular forces bind the molecules of the
solvent to a polymeric net, thus decreasing the
mobility of these molecules and producing a
structured system with increased viscosity .
Recent Advances in Semisolids
Hydrogel (cont(.
Example: In peroral administration, hydrogels
can deliver drugs to four major specific sites;
mouth, stomach, small intestine and colon.

By controlling their swelling properties or
bioadhesive characteristics in the presence of a
biological fluid, hydrogels can be a useful device
for releasing drugs in a controlled manner at
these desired sites .
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Recent Advances in Semisolids
Hydrogel (cont(.
Additionally, they can also adhere to certain
specific regions in the oral pathway, leading to a
locally increased drug concentration, and thus,
enhancing the drug absorption at the release
site.
Example: Oral anesthetic gel for the temporary
relief of minor irritation and pain associated with
minor dental procedures; minor irritation of the
mouth or stomatitis .
Recent Advances in Semisolids
Thermosensitive and pH-senstive sol-gel
reversible hydrogels :
They are the aqueous polymeric solutions which
undergo reversible sol to gel transformation
under the influence of environmental conditions
like temperature and pH which result in in situ
hydrogel formation .
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Recent Advances in Semisolids
Thermosensitive sol-gel reversible hydrogels
(cont . (
Example; The goal of oral insulin delivery devices is to
protect the sensitive drug from proteolytic degradation in
the stomach and upper portion of the small intestine .The
use of pH-responsive, poly (methacrylic-g-ethylene
glycol) hydrogels as oral delivery vehicles for insulin
were evaluated .
In the acidic environment of the stomach, the gels were
unswollen due to the formation of intermolecular polymer
complexes. Insulin remained in the gel and was
protected from proteolytic degradation .
In the basic environment of the intestine, the complexes
dissociated which resulted in rapid gel swelling and
insulin release