Semisolid

Dosage
Forms
Introduction 1

q Semisolid dosage forms are dermatological preparations intended for application

externally on the skin to produce local or systemic effect.
q A well formulated pharmaceutical semisolid should be therapeutically effective &
cosmetically appealing , with a major effort in the medical direction.

Semisolids

Poultices Rectal &

Rigid
Ointments Creams Pastes Gels Emulgels Plasters Vaginal
(Cataplasms) Foams
Semisolids
Dosage Forms
Ointments 2

Introduction
Ointments are viscous, semisolid preparations with or without medicament, intended for external
application to the skin or mucous membranes.
q They have plastic type rheology i.e. they have specific yield value & resistance to flow drops as
application to skin is continued.

*Non-medicated ointments are used for emollient ,protective & lubricating effect on skin
Ointments 3

Formulation

1.Drug :
q It should have sufficient solubility in the respective vehicle but must not posses a very high affinity
towards it.
q Percutaneous absorption occurs by passive diffusion & depends on conc. of drug in formulation.

2. Ointment Bases :
The USP classifies ointment bases in 4 categories :
USP
Ointment
Bases

Water-
Hydrocarbon/
Absorption removable / Water Soluble
Oleaginous Emulsifying
Bases Bases Bases
Bases

Anhydrous Emulsion
form Form
Ointments 4

Formulation

3. Other Bases :
q Bases called polyols include hygroscopic bases like : glycerin, sorbitol(70%), propylene glycol.
q They are used for their humectant, emollient, anti-drying & anti-rolling properties.

4. Other additives :

• Added for skin compatibility , • Unsaturated Oily phase more • Oily prepn. Not a good media • Natural & certified dyes
drug solubility & stability prone to oxidation for microbial growth may be used if req. Eg D&C
• Skin has weak acidic nature ; • Oil soluble antioxidants more • Ointments containing water Red 22 (Eosin), D&C Yellow
tolerates weakly acidic suitable (BHT, BHA, require preservatives 7 (Flourescin) etc
formulations better tocopherol, propyl/methyl • Eg : methyl/propyl paraben, • Flower based perfumes
• Eg : sodium acetate, gallate Dowicil, benzoic acid & salts, preferred Eg: Lavender ,
potassium metaphosphate • Water soluble anti-oxidant BKC, phenyl mercuric salts Rose ,Jasmine
useful if water soluble
/washable base used.

Organoleptic
Buffers Antioxidants Preservatives
additives
Ointments 5

Compounding
Compounding of
Ointments

Incorporation Method Fusion Method

q Incorporation Method :
• Also known as levigation, trituration or mechanical mixing method

q Fusion Method: This method is suitable when:

• Ingredients are solid at room temp. & do not lend themselves well to mixing by incorporation. Eg :
hard paraffin, beeswax, wool alcohols, stearyl/cetyl alcohol etc.
• Solid drugs which are readily soluble in melted base
• Incorporation of significant amount of water in absorption base.
Ointments 6

Compounding

Incorporation Method Fusion Method

Size Reduction Grate the waxy base
(size sieve no 85)
Melt using water bath
Levigation
Melt bases together (High M.P base first, mix low M.P base in it)

Mixing with Base Solution of soluble drug Dissolve oil & heat stable
drug
Spatulation Trituration Add small volume phase Make aqueous solution of heat stable
in large volume phase drug

Addition of base for q.s Cool with stirrimg

Addition of insoluble
drug
Soft mass at 40°C
Homogenization Mixing of volatile / heat
unstable drug.

Filling
Homogenization Filing
Ointments 7

Compendial Requirements
q Microbial Content
• Ophthalmic preparations must be sterile ; preprarations Microbial
Minimum Fill
Content
containing water must include preservatives.
• Microbial limits are stated fo certain articles in the USP Compendial
Requirements
• Eg : Betamethasone
Packaging
Valerate Ointment, USP, must meet the requirements of the tests Additional
,Storage,
for absence of Staphylococcus Standards
Labelling
aureus and Pseudomonas aeruginosa.
• USP chapter “Microbiological Attributes of Nonsterile
Pharmaceutical Products” emphasizes :
• strict adherence to environmental control
• application of good manufacturing practices to minimize both the
type a&nd the number of microorganisms in unsterilized
pharmaceutical products
Ointments 8

Compendial Requirements
q Minimum Fill
• The USP's minimum fill test is determination of the net weight Microbial
Minimum Fill
Content
or volume of the contents of filled containers to ensure proper
contents compared with the labeled amount. Compendial
Requirements

Packaging
q Packaging, Storage & Labeling ,Storage,
Additional
• In addition to the usual labeling requirements for Standards
Labelling
pharmaceutical products, the USP directs the labeling for
certain ointments and creams including proper storage
conditions, dosing and administration

q Additional Standards (USP)

• Viscocity
• In vitro drug release (Diffusion cell studies)
Ointments 9

Evaluation
Melting
Point

Non-
Solubility
Irritancy

Evaluation
Rate of
Absorption Consistency

Identification Rheological
of API /Assay Properties
Ointments 10

Marketed Formulations
Creams 11

Introduction
Pharmaceutical creams are semisolid preparations containing one or more medicinal agents dissolved or
dispersed in either a water-in-oil (W/O) emulsion or an oil-in water (O/W) emulsion or in another
type of water-washable base.

q Creams are less greasy & easier to apply than ointments

q The cool feeling due to evaporation of water gives a soothing feeling to the inflamed areas
q Creams interfere less with skin functions & have more skin contact than ointments
q Creams are physically more stable than liquid emulsions due to reduces creaming & coalescence

Creams

Oily Creams Aqueous Creams

Creams 12

Introduction
Creams

Oily Creams Aqueous Creams

Oily Creams Aqueous Creams

q These are w/o emulsions. q They are o/w emulsions.
q Contain lipophilic emulsifying agents like wool q Contain ow emuslifiers like monovalent soaps
fat, wool alcohols, divalent soaps of fatty acids of fatty acids, hydrophilic surfactants, PEG
or fatty acid esters of sorbitan(Spans) derivatives of sorbitan fatty acid esters (
q Used as emollients & cleansing creams. Tweens)
q They are more useful as water washable bases
q On application , water evaporates & deposits
drug on skin
Creams 13

Introduction

Vanishing Steroidal
Creams Creams

Emollients Anti-
Keratolytic / Cold
Topical anti-
inflammatory Pruritic
Creams Creams
creams Creams

Creams Creams
Topical
Skin Antifungal Anti-Acne
Cleansers Sunscreens Creams
Creams
Barriers & Topical
Protective Antibacterial
Creams Creams
Creams 14

Formulation
Creams are an extension of oleaginous ointments.
Liquid emulsions
(oil, water & surfactants) + Stiffening Base Semisolid Creams

Absorption Base Type Surfactant Base Type Soap Type

• They absorb water & form w/o • Ionic & non-ionic surfactants • These are semisolid soap
emulsions are both used. emulsions
• Eg : lanolin ( 70% wool fat ; • Non-ionic creams are non-toxic • Soap is formed in situ by
30% water) & suitable for application on reaction of a base with a fatty
• Oily Cream IP contains wool broken skin. acid (soaps made from TEA are
acohol : water (1:1) • Aqueous Cream BP is a o/w neutral)
emulsion, 30% emulsifying • Eg : cerotic acid-borax soap is
ointment as base ; 69.9% water formed in beeswax-borax
;0.1 % preservative cream(cold cream)
Creams 15

Compounding
Separate ingredients in 2 phases

Lipid Phase Aqueous Phase

(all water insoluble ingredients) (all water soluble ingredients)

Drug
(heat-stable)

Heat to M.P of highest melting ingredient Heat to M.P of highest melting ingredient

Mixing
(continue until cooling to promote uniform mixing)

Add aqueous phase to lipid phase

Drug(heat unstable)
Levigation, Roller milling)
High Shear Homogenization
(reduces particle size & promotes physical stability)

Filling
Creams 16

Marketed Formulations
Gels & Jellies 17

Introduction
• Gels (sometimes called jellies) are transparent to opaque semisolid systems
consisting of dispersions/suspensions of small or large molecules in an aqueous
liquid vehicle rendered jellylike by the addition of a gelling agent.(forms 3D
colloidal network structure)
q Gelling agents include carbomer ,cellulose derivatives (HPMC, MC,HPC) &
natural gums like tragacanth

• Gels are more rigid than jellies. Jellies contain more fluid & less crosslinking .
Fig : Representation of gel network

• Properties
q They have viscoelastic properties.
q The 3D matrix gel structure breaks easily on shaking / squeezing the tube.
(easy skin application)
q Applied on skin , mucous membranes, eyes & cosmetics like dentrifices, skin
& hair preparations.
Gels & Jellies 18

Introduction
Types of Gels

Nature of
No of Phases Colloidal Phase Solvent used Uses

Xerogels (Low Lubricating Medicated

1 Phase Gels 2Phase Gels Inorganic Gels Organic Gels Hydrogels Organogels solvent conc.) gels Gels

Dermatologic
Dental al Nasal Ophthalmic Vaginal

1 Phase Gels : Gels in which the 2 Phase Gels : Gels consisting of floccules of small distinct
macromolecules are uniformly distributed particles is termed a
throughout a liquid with no apparent boundaries between the two-phase system, often referred to as a magma Eg : Magnesia
dispersed macromolecules Magma ( milk of magnesia)
and the liquid.
Inorganic Gels : Contain gelling agents such as bentonite, Organic Gels : Contain gelling agents like carbomer, poloxamer,
hectorite & aluminium hydroxide PVA & other polymers
Hydrogels : Aqueous gels containing an insoluble polymer . Organogels : Hydrophobic gels containing a non-aqueous
They contain water, glycerin or propylene glycol gelled with solvent in the continuous phase.(liquid paraffin with colloidal
hydrocolloids. silica, metallic stearates,PEG etc)
Gels & Jellies 19

Formulation
• The main ingredients which are used in the formulation of gels includes:

Gelling Agent

Buffers

Preservatives

Anti-oxidants

Flavoring & Coloring Agents

Gels & Jellies 20

Compounding
• There are 3 main methods :
q Fusion Method
This is used when waxy materials are employed as gelling agents in non-polar media. The waxy
material is first melted followed by addition of drug. Stirring is continued until aa uniform gel is
formed on cooling

q Cold Method
In this method , water is cooled to 4-10ºC & placed in a mixing container. Gelling agent is slowly added
& agitated until solution is complete. Temperature is maintained below 10ºC. Drug is added in
solution form slowly with gentle mixing.

q Dispersion Method
In this, gelling agent is dispersed in water with stirring at 1200 rpm for 30 mins. Drug is dissolved in
non-aqueous solvent with preservative. This solution is added in the above gel with continuous
mixing
Gels & Jellies 21

Marketed Formulations
Emulgels 22

Introduction
• Emulgels are modified gels or combination of
emulsions & gels which allow delivery of hydrophobic
drugs as an aqueous gel dosage form.

• Novel polymers have been developed with

complex functions as emulsifiers and thickeners.
The gelling capacity of these compounds allow
the formulation of stable emulgels by decreasing
surface & interfacial tension and at the same time
increasing the viscosity of the aqueous phase.

• Presence of gelling agent in aqueous phase of

classical emulsion converts it into an emulgel. Fig : Emulgel
Emulgels 23

Introduction
• Advantages of Emulgels

Hydrophobic drugs can

It shows better It has better loading
be easily incorporated
stability. capacity.
into gels.

Production feasibility
No need of intensive
and low preparation Controlled release
sonication.
cost.
Emulgels 24

Formulation
q Properties of excipients :
• They must be non-toxic.
• They must be commercially available in
applicable grade.
• Their cost must be acceptably cheap.
• They must not be contraindicated.
• They must be physically and chemically
stable by themselves & in combination
with drugs & other components.
• They must be color compatible
Emulgels 25

Compounding

Evaluation

Physical Appearance Rheological Studies

Spreadability Skin Irritation Study

Pastes 26

Introduction
• Pastes are ointment like preparations containing a high % of insoluble solids in them (usu 25-50% or
higher). They have good skin adhesion & form a thick coat.

q They are less greasy, stiffer & more absorptive than ointments
q Preferred over ointments for treating oozing lesions & absorb serous secretions.
q Produce protective barrier on skin due to heavy consistency (localize action on skin)
q Less macerating as they allow perspiration to escape due to porous nature.

• Toothpastes are dentrifices used for cleaning the teeth & providing a refreshing mouth feel. As per USP
29, a dental paste is intended for adhesion to the mucous membranes for local action. (Eg :
Triamcinolone Acetonide Dental Paste)
Pastes 27

Formulation Thickening
agents
Humectants

Bases Preservatives

Drug Pastes Organoleptic

additives

Oleaginious Base Water Miscible Base Hydrocolloid Base

Lassar’s Paste BP, zinc Resorcinol & Sulfur Paste Toothpastes, Unna’s Paste
oxide coal tar paste BPC, BPC, Magnesium Sulfate IP
zinc oxide paste IP paste BPC, titanium
dioxide paste BPC
Pastes 28

Compounding

Trituration Method Hydrocolloid Method

(for pastes containing oleaginoius / (for pastes containing hydrocolloud as
emulsifying base thickener)

Mix drug(solid) with a portion of congealed base Sprinkle hydrocolloid over humectant under
directly / after levigation agitatiaon

Add remaining base by trituration Add water phase containing soluble additives

Mix drug with above & homogenize to produce

Disperse well & ensure unifrom mixing of solids. a smooth paste.
Pastes 29

Marketed Formulations :
Poultice 30

Introduction
• Poultices are viscous pasty preparations applied hot onto the skin to reduce inflammation or to act as
counter-irritants. The material possesses the properties of heat-retention & absorption, due to which
they absorb infected fluid from the tissue when used on boils.

• Eg : Kaolin Poultice IP
q Heavy Kaolin , fine : 5.27 g
q Boric Acid , fine : 4.5 g
q Methyl Salicylate : 0.2ml
q Mentha Oil : 0.05mL
q Thymol : 0.05mL
q Glycerin : 4.25g

Fig : Clay Poultice

Plasters 31

Introduction
• Plasters are solid/ semisolid masses made by incorporating medicaments on resinous or waxy bases ,
which are melted & spread on a suitable backing material . They are intended for external application
to provide protection , mechanical support or for local / systemic effects.

Formulation
• salicylic acid, belladonna extract, capsicum
Medicaments used oleoresin, zinc oxide, menthol , thymol etc

• gum resins, oleoresins & waxes ( impart

Bases used firmness & cohesiveness to product )

• paper wool , cotton, rayon ,muslin, silk,

Backing Material linen, rubber or plastic.
Plasters 32

Formulation
• Backing material properties:
q Cotton / Cotton wool backing : Provides support & a feeling of warmth
q Porous Plastic : Completely permissible to water vapour & air ; hence prevents wound maceration
& delay of healing
q Waterproof plastic adhesives : Allow complete exclusion of water vapour & air.
q Adhesive Plaster : Adhesive base containing 30% pure rubber mixed with filler such as zinc oxide.
Plasters 33

Compounding

Lump free mass

Backing Semisolid Semisolid mass at moderate
material is cut mass is is mixed well temperature is Preparation is
into required prepared by to remove spread on allowed to dry.
shape & size fusion method lumps backing material
evenly.
Excipients in
Semisolid
Formulations
Ointment Bases 34

Types
Ointment bases are divided into 4 groups as per USP:

Oleaginous Absorption
Bases Bases

Water- Water
Removable Soluble
Bases Bases
Ointment Bases
Types
q Oleaginous Bases
• Also termed hydrocarbon bases
• They have emollient effect on skin
• Water and aqueous preparations may be
incorporated, but only in small amounts and
with some difficulty
• Eg: Petrolatum, white petrolatum, white
ointment, and yellow ointment.
• Liquid petrolatum (mineral oil) used as the
levigating agent : when powdered
substances are to be incorporated into
hydrocarbon bases
35
Petrolatum, USP, is a purified mixture of White Petrolatum, USP, is a purified
semisolid hydrocarbons obtained from
petroleum..
mixture of semisolid hydrocarbons from
petroleum that has been wholly or nearly
Petrolatum is also known as yellow
petrolatum and petroleum jelly
decolorized White petrolatum is also
known as white petroleum jelly.
Oleaginous
Bases
Yellow wax is the purified wax obtained
White Ointment, USP. This ointment
differs from yellow ointment by
from
the honeycomb of the bee Apis mellifera..
substitution
of white wax (bleached and purified
Also called simple ointment, it has a
slightly greater viscosity than plain
yellow
wax) and white petrolatum in the
petrolatum formula
Ointment Bases 36

Types
q Absorption Bases
• These bases may be used as emollients, although they do not provide the degree of occlusion
afforded by the oleaginous bases.
• Not easily removed from the skin with water washing, because the external phase of the
emulsion is oleaginous.
• Useful as pharmaceutical adjuncts to incorporate small volumes of aqueous solutions into
hydrocarbon bases (accomplished by incorporating the aqueous solution into the absorption
base and then incorporating this mixture into the hydrocarbon base)
• Types:
Result in w/o emulsion Are w/o emulsions (Emulsion bases)
Permit the incorporation of aqueous Permit the incorporation of additional
solutions resulting in the formation of quantities of aqueous solutions
waterin-oil (W/O) emulsions
Eg: Hydrophilic petrolatum Eg :Lanolin
Ointment Bases 37

Types
q Water Removable Bases
• Water-removable bases are oil-in-water emulsions commonly called creams
• They are easily washed from skin and are often called water-washable bases as their external
phase is aqueous.
• They may be diluted with water or aqueous solutions. They can absorb serous discharges
• Eg : Hydrophilic Ointment USP
Ointment Bases 38

Types
q Water Soluble Bases
• Water-soluble bases do not contain oleaginous components
• They are completely water washable and often referred to as greaseless.
• They mostly are used for incorporation of solid substances.
• Large amounts of aqueous solutions are not effectively incorporated into these bases as they
soften on addition of water.
• Eg :Polyethylene glycol Ointment NF
Ointment Bases 39

Factors influencing choice of base:

Selection of the base to use in the formulation of an ointment depends on careful assessment of a
number of factors, including the following:

q Desired release rate of the drug substance from the ointment base
q Desirability of topical or percutaneous drug absorption
q Desirability of occlusion of moisture from the skin
q Stability of the drug in the ointment base
q Effect, if any, of the drug on the consistency or other features of the ointment base
q Desire for a base easily removed by washing with water
q Characteristics of the surface to which it is applied
Creams 40

Preservatives
The following three criteria are considered critical for preservative selection:
(i) the preservative system must exhibit the required antimicrobial activity in the proposed formulation
over the duration of the product shelf life;
(ii) The preservative system must be nontoxic, nonirritant and nonsensitizing for the proposed method
of application for the cream;
(iii) It must be compatible with the product (particularly its pH) and package.

Commonly used preservatives include:

• Benzyl alcohols
• Propylparabens
• Methylparabens
• Chlorocresol
• Imidazolidinyl urea (Germaben)
• Sodium benzoate
Creams 41

Anti-oxidants
Antioxidants are often used to reduce oxidation of active substances and excipients in creams.
Creams 42

Emollients
Emollients are often added to cream formulations to modify either the characteristics of the
pharmaceutical vehicle or the condition of the skin itself to promote penetration of the active ingredient
to act either locally or systemically.

• The stratum corneum, being keratinized tissue, behaves as a semipermeable artificial membrane, and
drug molecules can penetrate by passive diffusion.
• Commonly used emollients include : glycerin, mineral oil, petrolatum, isopropyl palmitate, and
isopropyl myristate.
Gelling Agents 43

Acrylic Acid Based Polymeric Gelling Agents

• Carbomers and Pemulen polymeric emulsifiers are acrylic acid polymers crosslinked with
polyalkenyl polyethers.
• Commonly used carbomers in pharmaceutical applications are :
• Carbomer 934P
• Carbomer 940 differ in mol. Wt. between crosslinks
• Carbomer 941

• Traditionally, Carbomers are used between concentrations ranging from 0.1% to about 1%
• Monovalent ions simply reduce the thickening efficiency of systems containing carbomer polymer by
reducing the overall charge repulsion along the polymer backbone.

Thickening Mechanism

Neutralization of polymer with Use of hydroxyl donor with

base (NaOH, Tris) polymer to form hydrogen bonds
Gelling Agents 44

Cellulose Based Polymeric Gelling Agents

• Commonly used cellulose derivatives include hydroxypropyl cellulose (HPC), carboxymethylcellulose,
and hydroxyethyl cellulose (HEC).

• The choice amongst these cellulose derivatives is primarily based on

• Type of formulation (aqueous or hydroalcoholic)
• Compatibility with the physiologically active ingredient and other excipients in the formulation.

• HPC is a nonionic water-soluble cellulose ether that is manufactured by reacting alkali cellulose with
propylene oxide at elevated temperatures. (used conc 0.2%)
• HEC is a nonionic water-soluble cellulose ether that is manufactured by reacting alkali cellulose with
ethylene oxide at elevated temperatures. It dissolves readily in hot or cold water. (used conc 1% - 2%)
Gelling Agents 45

Natural Gelling Agents

Commonly used natural gelling agents are xanthan gum, gellan gum, pectin,
and gelatin.

• Xanthan gum and gellan gum are high molecular weight polysaccharides
produced by microbial fermentation.
• Gellan gum is a gelling agent, effective at extremely low use levels,
forming solid gels at concentrations as low as 0.1% Fig : Pectin

• Pectins are a family of partially methyl esterified polysaccharides

produced from citrus peel and sugar beet pulp by extraction and
controlled de-esterification. Types:
• high methoxyl (HM) pectin
• low methoxyl (LM) pectin.
Permeation Enhancers 46
• Permeation enhancers are a group of chemicals
which interact with stratum corneum components to
increase transdermal drug delivery
• Act by disrupting the highly organized lipid bilayer
packing through interacting with intercellular proteins,
by increasing partitioning into the membrane or by a
combination of these mechanisms.

• Eg : Water (safest & most widely used)

• Ethanol (disrupt intercellular lipid packing)
• Small aprotic solvents (DMSO) (interact with lipid
bilayer head groups in the stratum corneum to
disrupt their close packing)
• Azone (1-dodecylazacyclohpetan-2-one) : insert
within the lipid lamellae to disrupt the endogenous
stratum corneum lipid bilayers
• Terpenes (fragrance agent) & surfactants
Fig : Adapted from Ref 5
Evaluation
Rheology 47

• Rheology is very important as these creams are

marketed in tubes or containers. The rheology or
viscosity should remain constant.

• As these products are normally non-Newtonian in

nature, the viscosity can be measured using
viscometers

• Rheologic measurements are utilized to

characterize the ease of pouring from a bottle,
squeezing from a tube or other deformable
container, maintaining product shape in a jar or
after extrusion rubbing the product onto and into
the skin and pumping the product from mixing
and storage to filling equipment.
Consistency Testing 48
This is determined using penetrometry:

Procedure:

Preparation of test sample: 3 methods (A,B,C)

A: Carefully and completely fill three containers without forming air bubbles. Level if
necessary to obtain a flat surface.

B: Apply a suitable shear to the samples for 5 min carefully and completely fill three
containers without forming air bubbles. Level if necessary to obtain a flat surface.

C: melt 3 samples carefully and completely fill three containers without forming air
bubbles. Level if necessary to obtain a flat surface.
Consistency Testing 49
Determination Of Penetration :
Place the test sample on the basis of the penetrometer. Verify that its surface is perpendicular to the
vertical axis of the penetrating object. Bring the temperature of the penetrating object to 25 ± 0.5oC and
then adjust its position such that its tip just touches the surface of the sample . Release the penetrating
object and hold it free for 5 sec. clamp the penetrating object and measure the depth of penetration.
Repeat the test with 2 remaining containers.

Result:
The penetration is expressed in terms of mm as the arithmetic mean of the three measurements. If any of
the individual results differ from the mean by more than 3%,repeat the test and express the results of the
6 measurements as the mean
In vitro Skin Penetration 50

In Vitro Skin Penetration is done by :

Flow Through Cell Franz Diffusion

They mainly have two compartments

1) Donor
2) Receptor Method:

The passage of
semisolid
Placed in preparation
Mouse skin or between the through the Sampling ( Franz
human cadaver Detection
two epidermal surface diffusion cell )
skin is taken to receptor
compartments.
compartment is
measured by
Irritancy Testing & Preservative Efficacy 51

Draize-
Shelanski
Repeat Insult
Patch Test
21 Day
Kligman
Cumulative
Maximization
Irritancy
Test
Patch Test

Irritancy
Testing
Other Tests 52

Content Uniformity
• A known weight of semisolid is taken & assayed for amount of drug.

Penetration

• A weighed quantity of semisolid is rubbed over skin for a given period of time & the unabsorbed
semisolid is collected & analysed . Difference in drug content is determined.

Absorption of drug in blood stream

• A standard quantity of semisolid is rubbed over skin for a given period of time Under std conditions,
the conc of drug is measured in the plasma or urine.
Industrial Processing 53

Purified
Water

Lab Scale(1x)
Insoluble Hydrocarbons
powders

Raw Hydrocarbon
Pilot Scale(10x)
Polyols waxes
Materials

Production Scale(100x)
Oils
Emulsifiers (mineral/
vegetable)
Fatty Acids &
Alcohols
Industrial Processing 54

Major Unit Processes

All the below mentioned processes can be performed
in a stainless steel steam jacketed kettle with
attached mixing element or homogenizer

Preparation of Oil & Aqueous

Phases

Mixing of Phases

Cooling of Semisolid Emulsion

Homogenization
Industrial Processing 55

Mixing of Semisolids
The problems that arise during the mixing of semisolids (ointments and
pastes) stem from the fact that, unlike liquids, semi-solids will not flow easily.
Material that finds its way to a ‘dead spot’ will remain there.

Mixers for semisolids:

q Planetary Mixers Agitator Type Mixers
q Sigma Blade Mixers
q Triple Roller Mills Shear Mixers
q Colloidal Mills

Fig : Factors affecting scale-Up of

semisolids mixing

Fig : Planetary Mixer Fig: Triple Roller Mill

Industrial Processing 56

Homogenization
Creams / Ointments requiring further treatment are
transferred to a homogenizer. Selection of homogenizer
is governed by
q Degree of shear stress required
q Rate of shear
Fig : Gear Pump Fig : Roller Mill

Types of homogenizers available :

q Low shear gear pump
q Roller mill
q Colloidal Mill
q Valve type homogenizer
q Sonic homogenizers

Fig : Colloidal Mill Fig : Valve Type Homogenizer

Industrial Processing 57

Low Energy Emulsification

Industrial Processing 58
Filling

q Filling Jars
• Semisolids prepared by fusion may be poured directly into the jar to
congeal in it. This must be done cautiously to prevent stratification of
the components
• In large-scale manufacture of semisolids, pressure fillers force the
specified amount of into the jar.
q Filling Tubes
• Industrially, automatic filling, closing, crimping, and labeling machines
are used for large-scale tube packaging of semisolid pharmaceuticals
• Depending on the model, machines have the capacity to fill about 1,000
to 6,000 tubes per hour.
• Rotary machines have four stations for tube feeding, cleaning, filling, and
closing
Summary 59

Classification

Industrial Semisolid
Processing Dosage Forms

Permeation Formulation of
Enhancers Semisolids

Evaluation
Methods for
Parameters of
Compounding
Semisolids
Excipients used
in semisolids
References 60

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2. Lachman, L., & Liebermann, H. A. (2013). The Theory and practice of industrial pharmacy. New
Delhi: CBS Publishers & Distributors Pvt. Ltd.
3. Katdare, A., & Chaubal, M. V. (2006). Excipient development for pharmaceutical, biotechnology, and
drug delivery systems. New York: Informa Healthcare
4. Remington, J. P., Allen, L. V., Adeboye, A., & Philadelphia College of Pharmacy (1822-1921). (2013).
Remington: The science and practice of pharmacy. London: Pharmaceutical Press.
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