FORMULATION OF SEMISOLID

DOSAGE FORMS

1
INGREDIENTS USED FOR
FORMULATING SEMISOLIDS INCLUDE

API,
Bases,
Antimicrobial preservative,
Chelating agents,
Humectants,
Fragrances.
2
ACTIVE PHARMACEUTICAL INGREDIENTS
Disease treated API
Keratolytic Salicylic acid

Acne Sulphur, Resorcinol

Antipruritic Benzocaine, Menthol, Camphor

Emollient Lanolin

Anti-inflammatory Corticosteroid

Antifungal Benzoic acid, Salicylic acid

3
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 bases.
B) Absorption bases.
C) Emulsion bases.
D) Water soluble bases.
E) Water removable bases.

4
 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 hydroxyl benzoate,

 Propyl- hydroxy benzoate,

 Chlorocresol,

 Benzoic acid,

 Phenyl mercuric nitrate,

 Benzalkonium chloride,

 Chlorhexidine acetate,

 Benzyl alcohol. 5
ANTIOXIDANTS: -
Example of commonly used antioxidants
include
Butylated hydroxy anisole (BHA, E320),
Butylated hydroxy toluene.

6
CHELATING AGENTS: -
chemicals that form soluble, complex
molecules with certain metal ions, inactivating
the ions so that they cannot normally react
with other elements or ions to produce
precipitates or scale
Example of commonly used chelating agents
include
Citric acid,
Maleic acid

7
HUMECTANTS: -
Example of commonly used humectants
includes
Poly Ethylene Glycol,
Glycerol or

Sorbitol

8
FRAGRANCES:-
Examples of widely use fragrances are
Lavender oil,
Rose oil,

Lemon oil,

Almond oil

9
 METHODS OF MANUFACTURING
AND QUALITY CONTROL OF
SEMISOLIDS

10
 There are four methods of preparation,

BY BY CHEMICAL BY OINTMENT
TRITURATION
BY FUSION REACTIONS MILLS

11
BY TRITURATION

 When base contain soft fats and oils or medicament is

insoluble solid or liquid, then this method is use.
 Application of shear forces.

 It is laboratory and small scale method mostly using

Mortar and Pastel.

12
BY FUSION

 When soft fats or waxes are to be incorporated with hard fats

or waxes then of this to be melted to get homogenous
mixture with stirring.

13
BY CHEMICAL REACTIONS
 In chemical method a new product is formed by
chemical reaction, which involves both fusion and
mechanical mixing.
 Best example of such method is Iodine ointment.

14
BY OINTMENT MILLS
 It is used for large scale production where triple roller
mill is utilized which is faster than others.

15
Quality assurance
and Quality Raw material In process Finished product
control of specification control specifications
semisolids 

16
17
1. Description

2. Solubility

3. Identity

a. Specific chemical test

b. Infrared absorption

c. Ultraviolet absorption

d. Melting range

e. Congealing point

f. Boiling point or range

g. Thin layer, paper, liquid or gas

chromatoghraphy 18
4. Purity and quality
 a. General completeness of solutions, pH, specific rotation, non-volatile residue, ash,
acid- insoluble ash, residue on ignition, loss on drying, water content, heavy
metals, arsenic, lead, mercury, selenium, sulphate, chloride, carbonates, acid value ,
iodine value, saponification value

b. Specific quality tests ,particle size, Crystallinity characteristics ,and polymorphic

forms

c. Specific purity tests , related degenerated products

5. Assay , calculated either on anhydrous or hydrous basis
6. Microbial limit test, especially for raw materials from natural sources
 
E. Test procedure
 
1. Compendial USP or NF references
2. Noncompendial, detailed analytical procedures, weights, dilutions, extraction,
19
normality, reagent, instrumentation used and procedure, if any calculation
IN PROCESS CONTROL

 Complete solubilization (if applicable)

 pH
 Viscosity measurement
 Uniformity of distribution of active
ingredients
 Physical stability
 Measurement of density or specific gravity.

20
FINISHED PRODUCT
SPECIFICATIONS

 MICROBIAL TEST
 PHYSICAL TESTS 
 CHEMICAL TESTS
 IN-VITRO RELEASE PROFILE TEST
 INSTRUMENTAL ANALYSIS

21
MICROBIAL TEST
 Topical preparations are not require being sterile.
 They must meet acceptable standards for microbial
contents
 USP chapter titled “Microbial Attributes of Non sterile
Pharmaceutical Products”.
 Betamethasone valerate ointment USP, must meet the
requirements of the tests for absence of Staphylococcus
aureus and Pseudomonas aeruginosa.

22
PHYSICAL TESTS 

23
CHEMICAL TESTS

 Chemical tests to be performed includes

Chemical potency test:-
 Can be performed by using Animal Models.
Content uniformity test:-
 Assay
pH measurement
 Ph-Meter

24
IN-VITRO RELEASE PROFILE TEST
 Skin penetration involves use of some variety of a diffusion cell like
 Franz cell and
 Flow through cell in which animal or human skin is fastened to a
holder and the passage of compounds from the epidermal surface to a
fluid bath is measured.
 Hairless rats were sacrificed
 The skin from the dorsal surface was excised, and the adherent fat and
subcutaneous tissue were removed.
 The skin was mounted on Franz diffusion cells with the epidermis
25
facing the donor compartment.
 For the skin retention studies, the donor cell was removed, and the
excess formulation was removed from the surface of the skin
using a cotton swab.
 The skin was then washed with 50% ethanol: water and blotted
dry with lint-free absorbent wipes.
 The entire dosing area (0.636 cm2) was collected with a biopsy
punch.
 Active drug content of epidermis and dermis was extracted using
a previously reported method.
 Briefly, the samples were homogenized and boiled for 10 minutes
in solvent.
 The samples were then centrifuged and the supernatant was
collected for analysis of drug by HPLC.
 The experiments were repeated at least 3 times using the skins
from different rats. 26
 GELS
 Controlledrelease gels 
 Organogels

 Extended release gels

 Amphiphilic gels

 Hydrophilic gels

 Non aqueous gels

 Bioadhesive Gels

 Thermosensitive sol-gel reversible hydrogels

 Complexation gels

27
 CONTROLLED RELEASE GELS 
 Drug delivery to nasal or ocular mucosa for either local or
systemic action suffers from many obstacles.
 Gel formulations with suitable rheological and mucoadhesive
properties increase the contact time at the site of absorption.
 However, drug release from the gel must be sustained if benefits
are to be gained from the prolonged contact time.
 Case Study:- Gelrite gels were formed in simulated tear fluid at
concentrations of polymer as low as 0.1%, and it was shown that
sodium was the most important gel-promoting ion in vivo.
28
 Kinetics:-

 It was possible to control the release of uncharged drug substances

by including surfactants that form micelles in the gel.

 The release depends on lipophillic interactions between the drug

and the polymer and/or the micelles.

 Controlled-release formulations of charged drugs could be

designed by mixing the drugs with oppositely charged

surfactants in certain fixed ratios.

 In this way, vesicles in which the drug and surfactant constituted

29

the bilayer formed spontaneously.

 ORGANOGELS
 Sorbitan monostearate, a hydrophobic nonionic surfactant,
gels a number of organic solvents such as hexadecane,
isopropyl myristate, and a range of vegetable oils.
 Gelation is achieved by dissolving/dispersing the
organogelator in hot solvent to produce an organic
solution/dispersion, which, on cooling sets to the gel state.

30
 Cooling the solution/dispersion causes a decrease in the
solvent-gelator affinities, such that at the gelation
temperature, the surfactant molecules self-assemble into
toroidal inverse vesicles.
 Further cooling results in the conversion of the toroids into
rod-shaped tubules. Once formed, the tubules associate with
others, and a three-dimensional network is formed which
immobilizes the solvent. An organogel is thus formed.

31
 Sorbitan monostearate gels are opaque, thermoreversible
semisolids, and they are stable at room temperature for weeks.
 Such organogels are affected by the presence of additives such
as the hydrophilic surfactant, polysorbate 20, which improves
gel stability and alters the gel microstructure from a network of
individual tubules to star-shaped "clusters" of tubules in the
liquid continuous phase.
 Another solid monoester in the sorbitan ester family, sorbitan
monopalmitate, also gels organic solvents to give opaque,
thermoreversible semisolids. 32
 EXTENDED RELEASE GELS
 TIMERx is a controlled release technology consists of an
agglomerated, hydrophilic complex that, when compressed, forms
a controlled-release matrix. The matrix, consisting of xanthan and
locust bean gums (two polysaccharides) combined with dextrose,
surrounds a drug core.
 In the presence of water, interactions between the matrix
components form a tight gel while the inner core remains
unwetted.
 The drug is encapsulated in the pores of the gel, and as the matrix
travels through the patient’s digestive system, the tablet swells and 33
begins to erode.
 This erosion allows the drug to “back-diffuse” out through the
gel-matrix at a controlled rate until the matrix erodes and a
majority of the drug is released.
 The fundamental component controlling the rate of release lies
in the properties of the gel matrix.
 Advantage of this system includes,
 a) Predictable modified release profile like zero order or first order
or initial immediate release kinetics
 b) It can be manufacture on standard manufacturing equipment.
 c) Cheap.
34