Integrated Physical Pharmacy and

Pharmaceutics II
Semisolid Dosage Forms

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 Content
 Introduction
 Classification of semisolid
 Rheological properties of semisolids
 Desired properties of semisolids
 Ointments and Pastes
 Creams and Gels

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 Objective
 After completion of this chapter, the student will be able to:

 Differentiate between the various types of ointment bases, based on their

physical and chemical properties

 List the criteria for the selection of an ointment base

 Describe the methods to incorporate (an) active ingredient(s) into an

ointment base

 Develop the knowledge and skills of extemporaneous preparation

(compounding) of semisolid

 Explain the difference between an ointment, a paste, a cream, and a gel

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 Introduction
 Dosage Forms
 Solid dosage forms
 Tablet, Capsule, Powder etc
 Semi-solid
 Ointments, Creams, Pastes, etc
 Liquid
 Solutions, Suspensions, Emulsions
 Gas
 Aerosol

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 Introduction cont’d
 Semisolid dosage forms are dermatological preparations

intended to be applied externally on the skin to produce local

or systemic effect.

 They have the property to cling to the skin or mucous

membrane for a protracted period of time.

 They may be applied to the skin, placed on the surface of the

eye, or used nasally, vaginally, or rectally.

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 Introduction cont’d
 Topical preparations are used for both local and systemic effects.

 Most of these preparations are used for the effects of the

therapeutic agents they contain.

 The unmedicated ones are used for their physical effects as

protectants or lubricants.

 Systemic drug absorption should always be considered if the

patient is pregnant or nursing.

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 Introduction cont’d
 Systemic delivery: Movement of substances from the skin

surface to the general circulation.

 It includes penetration through the stratum corneum

→Diffusion through each layer of the skin → Uptake by the

capillary network at the dermo-epidermal junction →
Finally transportation to the target tissues to achieve
therapeutic action

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 Classification
 Ointments
 Pastes
 Cream
 Gels

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 Classification cont’d
 Ointments: Semisolid preparations intended for external application to
the skin or mucous membranes
 Bases: The semisolid vehicle into which drug substances may be
incorporated in preparing medicated ointments.
 Ointment bases recognized for use as vehicles fall into four general
classes:
 hydrocarbon bases

 absorption bases

 water-removable bases

 water-soluble bases.

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 Classification cont’d
 Cream: dosage forms containing one or more drug substances
dissolved or dispersed in a suitable base.
 Traditionally been applied to semisolids that possess a relatively
fluid consistency formulated as either water-in-oil or oil-in-water
(emulsions).
 More recently the term has been restricted to products consisting
of oil-in-water emulsions or aqueous microcrystalline
dispersions of long-chain fatty acids or alcohols that are water
washable and more cosmetically acceptable.

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 Classification cont’d
 Gels: are transparent or translucent, non-greasy,
semisolid systems generally applied externally for
their medication, lubrication and miscellaneous
purposes.

 Pastes: semisolid dispersion system, where a solid

particles (> 25%, e.g. ZnO) are dispersed in ointment

bases - mostly oleaginous (Petrolatum)

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 Desired Properties of Semisolid Dosage Forms

Physical Properties Physiological Properties

o Smooth texture o Non irritating
o Elegant in appearance o Do not alter membrane /
o Non dehydrating skin functioning
o Non gritty
o Miscible with skin
o Non greasy and non
secretion
staining
o Non hygroscopic o Have low sensitization
index

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 Rheological properties of semisolids
 Semisolid dosage forms exhibit different
rheological properties
 Semisolids do not flow at low shear stresses but
undergo reversible deformation like elastic solids.
 When a characteristic shear stress, called the yield
value or yield stress, is exceeded, they flow like
liquids

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 Rheological properties, cont’d
 At a stress below yield value no flow will be

formed but only elastic deformation.

 When the yield stress is exceeded, the network is

partly ruptured and flow occurs.

 Gels or jellies are characterized by a comparatively

high degree of elasticity.

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 Rheological properties, cont’d
 They undergo rather large elastic deformation at
shear stresses below the yield value, from which
they recover their shape when the stresses are
removed.
 Recoverable deformations of 10 to 30% are not
unusual, especially for polymer gels.
 Clay gels are less elastic and more like pastes.

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 Rheological properties, cont’d
 Pastes have little elasticity

 Cannot recover their shape except from very small

deformations.
 At stresses above their yield values, pastes turns into
free-flowing liquids (plasticity).
 Brownian motion builds up the networks in gels and
pastes and restores them when they have been ruptured
by stress higher than yield stress.

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 Rheological properties, cont’d
 Plastic materials:- ointments and pastes, creams, butter ,

margarine…

 Semisolids with high yield values are described as “hard”.

 When their plastic viscosity is high, they are described as “stiff”.

 Instrument for determining the rheological properties of

pharmaceutical semisolid are:
 Rotational viscometer.

 Cone-plate viscometer

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 Transdermal drug delivery
 Percutaneous absorption : the absorption of substances from
outside the skin to positions beneath the skin, including
entrance into the blood stream.
 Drugs may penetrate intact skin after topical application
through
 The walls of the hair follicles,
 The sweat glands
 The sebaceous glands,
 Trough the cells of the horny layer

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 Transdermal cont’d
 The main route for the penetration of drug is generally

through the epidermal layers

 The stratum corneum is the outermost ‘horny’ layer of skin,

comprising about partially desiccated, dead, keratinized

epidermal cells.

 It is the rate-limiting barrier to percutaneous drug transport

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 Transdermal cont’d
 Transport of lipophilic drug molecules is facilitated by their
dissolution into intercellular lipids
 Absorption of hydrophilic molecules into skin can occur through
‘pores’ or openings of the hair follicles and sebaceous glands
 But, the relative surface area of these openings is barely 1% of the
total skin surface which limits the amount of drug absorption
 Permeation of the substances can occur by diffusion via:
 Transcellular penetration

 Intercellular penetration

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 Transdermal cont’d
Factors Affecting Percutaneous Absorption

Nature of the skin

Nature of the drug

Nature of vehicle

Miscellaneous Factors

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 Transdermal cont’d
 Maximizing the bioavailability of drug to skin
 Drug or prodrug selection
 Hydration
 Ultrasounds(phonophoresis)
 Iontophoresis
 Stratum corneum removal
 Chemical penetration enhancers

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 Chemical penetration enhancers
Materials used to enhance absorption:
 surfactants, dimethylsulfoxide (DMSO), dimethylacetamide,

dimethylformamide, alcohol, acetone, propylene glycol, and

polyethylene glycol.

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 Mechanism of action for percutaneous absorption enhancers

 Reduction of the resistance of the stratum corneum

 Alteration of the hydration of the stratum corneum

 Effecting a change in the structure of the lipids and

lipoproteins in the cellular channels, through denaturation

 Carrier mechanism in the transport of ionizable drugs

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 Iontophoresis and Sonophoresis
 Iontophoresis: the delivery of charged chemical compounds across

the skin membrane using an applied electrical field. Eg: lidocaine,

amino acids/peptides/insulin, verapamil, and propanolol

 Sonophoresis : high-frequency ultrasound, is also being studied as

a means to enhance transdermal drug delivery Eg.:

hydrocortisone, lidocaine, and salicylic acid in such formulations
as gels, creams and lotions

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 Rational of transdermal drug delivery
 Manipulate the barrier function of the skin:

 Topical antibiotics and antibacterials help a damaged

barrier to ward off infection

 Sunscreen agents protect the viable tissues from
ultraviolet radiation
 Emollient preparations restore pliability to a desiccated

horny layer

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 Rational… cont,d
 Directing drugs to the viable skin tissues

 Delivering drugs skin for systemic treatment.

 Eg., transdermal therapeutic systems provide systemic therapy for

conditions such as motion sickness, angina and pain.

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 Advantage of TDD
 Avoids gastrointestinal drug absorption difficulties

 Substitutes for oral administration of medication when that

routes is unsuitable.

 Avoids first-pass effect

 Provides the capacity for multiday therapy with a single

application

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 Advantage of TDD, cont’d
• Provides sustained and controlled administration(for chronic

diseases).

• Provides capacity to terminate drug effect rapidly.

• Permit self administration

• Extends the activity of drugs having short half-life through

the reservoir of drug present in the therapeutic delivery

system

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 Disadvantage of TDD
 unsuitable for drugs that irritate or sensitize the skin.

 Only relative potent drugs are suitable candidates

 Technical difficulties are associated with the adhesion of the

systems to different skin types and under various

environment conditions

 Poor diffusion of large molecules

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 Ointments and Pastes

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  Pharmaceutical ointments are semisolid systems that are applied
externally
 primarily to the skin

 mucous membranes e.g. the rectum, the vagina, the eye.

 Medicated ointments: for the treatment of infection, inflammation

…
 Non-medicated ointments are commonly used as emollient/
lubricating properties.

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 Advantages of pharmaceutical ointments, pastes, and gels

 Ointments easily spread on skin, being retained at the site of

application as an occlusive layer

 thereby preventing moisture loss from the skin.

 useful in restoration of the physical characteristics of the skin (e.g.

due to inflammation)

 Ointments are associated with lubricating properties that may be

employed to reduce trauma of an affected site upon spreading.

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  Pharmaceutical pastes are generally composed of ointment

bases that contain a high concentration of dispersed drug.

 The viscosity of pharmaceutical pastes is greater than that of

pharmaceutical ointments

 The increased viscosity of pharmaceutical pastes ensures that

a thick film of the dosage form is applied to the site of action

 shows excellent persistence

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 Advantages, Cont’d
 Due to the high solids content, Paste
 act to absorb moisture and chemicals within the exudates.

 enables to be used as a sun block.

 The chemical stability of therapeutic agents that are prone to

hydrolysis will be dramatically enhanced by formulation within
pharmaceutical ointments and pastes.
 Pharmaceutical gels may be formulated to provide excellent
spreading properties and will provide a cooling effect due to
solvent evaporation.

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 Disadvantage
 Ointments are generally greasy and difficult to remove (cosmetically
unacceptable).
 Pharmaceutical pastes are generally applied as a thick layer at the
required site (cosmetically unacceptable).
 Staining of clothes is the problem

 Problematic in ensuring spreading of the dosage form over the affected

site.
 The viscosity of pharmaceutical ointments, and in particularly pastes

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 Disadvantage
 Pharmaceutical ointments may not be applied to exuding sites

 Problems concerning drug release from pharmaceutical ointments

may occur if the drug has limited solubility in the ointment base

 Pharmaceutical pastes are generally not applied to the hair

 due to difficulties associated with removal.

 Drugs that are prone to hydrolysis should not be formulated into

aqueous gels.

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 Ointments
 Classification of Ointments

According to their therapeutic properties based on penetration

According to their therapeutic uses.

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 Ointments, cont’d
 According to their therapeutic properties based on penetration

1. Epidermic ointments
• Act on epidermis & produce local effect.
• Used as protectives, antiseptic, local anti-infectives & parasiticides.
2. Endodermic ointments
 Act on deeper layers of cutaneous tissues.
 Partially absorbed & act as a emollients, stimulants & local irritants.
3. Diadermic ointments
 Meant for deep penetration and release the medicaments and produce
systemic effects.

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 Ointments, cont’d
 According to their therapeutic uses. :

1. Antibiotic ointments: Used to kill micro-organisms. Eg-

bacitracin, Neomycin, Chlortetracylclines, etc.
2. Antifungal ointments- Inhibit or kill the fungi. Eg- Benzoic acid,
salicylic acid, nystatin etc.
3. Anti-inflammatory ointments: Relieve inflammatory, allergic &
pruritic conditions. Eg- Betamethasone valerate,
Hydrocortisone & its acetates.

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 Ointments, cont’d
4. Anti-pruritic ointments: Relieve itching Eg- Benzocaine & coal
tar

5. Astringent ointments: -Causes contraction of skin & decreases

discharge. Ex- Calamine, ZnO, Acetic acid, Tannic acid

6. Anti eczematous Ointments: -Prevent oozing & excretion from

vesicles on the skin. Ex- Hydrocortisones, ichthamol, coal tar &
salicylic acid

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 Ointments, cont’d
7. Keratolytic Ointments: Used to remove or soften the horny
layer of the skin. E.g- Resorcinol, salicylic acid & sulphur
8. Counter-irritant Ointments: Applied locally to irritate skin,
thus reducing or relieving another irritation or deep seated pain.
E.g- methyl salicylate, iodine, oleoresin
9. Protectant Ointments: Protect skin from moisture, air, sun
rays, chemicals. E.g-Calamine, ZnO, silicones, titanium dioxide
etc.

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 Ointments, cont’d
10. Antidandruff ointments: Eg- Salicylic acid, cetrimide.

11. Ointment For Psoriasis treatment: E.g.- coal tar,

coticosteroid, & salicylic acid mixed with suitable ointment
base.

12. Parasiticide ointments: Destroy or inhibit living

infestation like ticks & lice. E.g.- Benzyl benzoate,
hexachloride, sulphur etc.

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 Ointments, cont’d
 The formulation of ointments and pastes involves the

dispersal or dissolution of the selected therapeutic agent into

an ointment base

 The physicochemical properties of the ointment base are

fundamental to:
 the clinical

 non-clinical performance of this type of dosage form.

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 Ointments, cont’d
 The choice of ointment base is dependent on several factors,
including:
1. Dermatological factors
 Absorption and penetration
 Effect on the skin
 Miscibility with skin secretion
 Compatibility with skin secretion
 Non-irritant (eye ointments)
 Emollient property
 Patient skin condition ( old, baby and young)
 the site of application;

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 Ointments, cont’d
2. Pharmaceutical factors
 the required rate of drug release;
 the chemical stability of the drug; and
 the effect of the therapeutic agent on formulation viscosity

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 Types of base for ointments and pastes
 There are four types of base that are used to formulate

pharmaceutical ointments and pastes:

1. Hydrocarbon

2. Absorption

3. water-miscible/removable

4. water-soluble.

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 Types of base, Cont’d
1. Hydrocarbon bases (Oleaginous bases):
 non-aqueous formulations, emollient

 restrict water loss from the site of application

 Due to the formation of an occlusive film

 Excellent retention on the skin

 Predominantly hydrophobic
 Difficult to remove from the skin by washing

 difficult to apply to (spread over) wet surfaces (e.g. mucous membranes, wet
skin)

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 Hydrocarbon base, Cont’d
 Small amount of water ( 5%) can be incorporated into it with

difficulty

 Can be protective to water labile drugs such as tetracycline

and bacitracin.

 Greasy and can stain clothing.

 Chemically inert

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 Hydrocarbon bases, Cont’d
 E.g. of hydrocarbon bases:

1. Petrolatum, USP
 Yellow petrolatum/petrolatum jelly /Vaseline
 Melts at 38-60oC

2. White petrolatum, USP

 Decolored petrolatum,
 White petroleum jelly/white vaseline

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 Hydrocarbon bases, Cont’d
3. Yellow ointment, USP
 Yellow beeswax (5% w/w) + petrolatum (95% w/w )

4. White ointment, USP

 White beeswax + white petrolatum

 Hydrocarbon bases frequently contain the following components:

 hard paraffin
 white/yellow soft paraffin
 liquid paraffin (mineral oil)

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 Hydrocarbon bases, Cont’d
Hard paraffin
 A mixture of solid saturated hydrocarbons that are derived from
petroleum or shale oil.
 a colourless or white wax-like material that is physically composed
of a mixture of microcrystal.
 The melting temperature of hard paraffin is between 47 and 65oc
and,
 used to enhance the rheological properties of ointment bases.

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 Hydrocarbon bases, Cont’d
White/yellow soft paraffin

 A purified mixture of semisolid hydrocarbons that are

derived from petroleum.

 Consists of microcrystals embedded in a gel composed of

liquid and amorphous hydrocarbons.

 The melting range of the soft paraffins is between 38 and 60o

c.

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 Hydrocarbon bases, Cont’d
 White soft paraffin and yellow soft paraffin (the former being

a bleached form of yellow soft paraffin)

 used as an ointment base without the need for additional

components, although it may be combined with liquid

paraffin

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 Hydrocarbon bases, Cont’d
Liquid paraffin (mineral oil, Liquid petrolatum)

 mixture of refined liquid saturated hydrocarbons obtained

from petroleum
 Levigating agent to incorporate lipophilic solids

 An excipient in topical formulations where its emollient

properties are exploited

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 Hydrocarbon bases, Cont’d
 usually formulated with white/yellow soft paraffin to achieve

the required viscosity for application to the required site.

 Formulations containing liquid paraffin require the

incorporation of an antioxidant
 due to the ability of this material to undergo oxidation

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 Absorption bases
 Absorption bases, unlike the hydrocarbon types, are hydrophilic
and, therefore,can absorb considerable amounts of water or
aqueous solutions.
1. Non-emulsified bases
 These bases absorb water and aqueous solutions to produce water-
in- oil ( W/O ) emulsions.
 Compared with the hydrocarbon bases:-
 They are less occlusive, nevertheless, are good emollients
 They assist oil-insoluble medicaments to penetrate the skin
 They are easier to spread.

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 Absorption bases, cont’
 Typically non-emulsified bases are commonly composed of:

 one/more paraffins, and

 a sterol-based emulsifying agent.

 Examples: (1) lanolin (wool fat); (2) wool alcohols; and (3)

beeswax (white or yellow).

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 Absorption bases, cont’
Lanolin (wool fat)
 Lanolin is a wax-like material that is derived from sheep’s
wool.
 It is available in two forms, termed Anhydrous lanolin (wool
fat) and hydrous lanolin.
 Anhydrous lanolin:
 called wool wax, wool fat, or wool grease,
 a greasy yellow substance
 contains < 0.25% of wate

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 Absorption bases, cont’
 Typically mixed with paraffins to produce an ointment base

 Can absorb approximately twice its own weight of water to

produce water in oil emulsions.

 The usual concentrations of lanolin used in ointments (e.g.

Simple Ointment BP) range from 5 to 10% w/w.

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 Absorption bases, cont’
 Wool fat is a major constituent of Simple Ointment B.P and
Eye Ointment Simple ointment B.P
Hard paraffin ………50g
 Cetosteryl alcohol….50g
 Wool fat……………..50g
 Soft paraffin……….850g
Eye Ointment B.P
 Liquid paraffin…..100g
 Wool fat…………100g
 Yellow soft paraffin……850g

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 Absorption bases, cont’d
Wool alcohols

 A crude mixture of sterols and triterpene alcohols

 Added to mixtures of paraffins (hard, so white/yellow soft or

liquid) to produce the required consistency.

 The inclusion of wool alcohols (5% w/w) results in a 300%

increase in the concentration of water e.g. wool alcohol

ointment B.P

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 Absorption bases, cont’d
2. Water in oil emulsions
 These are similar in properties to the previous group and are
capable of absorbing water.
 Absorption bases are less occlusive than the hydrocarbon bases and
easier to spread.
 They are good emollients.

 Eg. hydrous lanolin, which is a mixture of lanolin and 25–30%

water.

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 Absorption bases, cont’d
 It is used alone as an emollient and is an ingredient of several

B.P. ointment bases, i,e Hydrous wool fat ointment Calamine

and coal tar ointment Methyl salicylate ointment

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 Absorption bases, cont’d
 Properties of absorption bases
 Non-emulsified absorption bases (anhydrous)
 Emollient
 Occlusive
 Absorbs water
 Greasy
 W/O emulsion
 Emollient
 Occlusive
 Contains water, absorbs additional water
 Greasy

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 Water-washable/removable bases
 Water-miscible bases that are used to form O/W emulsions.

 They can be applied to scalp and other hairy regions.

 There are 3 official anhydrous water-miscible bases.

 Emulsifying ointment B.P – anionic

 Cetrimide emulsifying ointment B.P – cationic

 Cetomacrogol emulsifying B.P- non-ionic

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 Water removable bases, cont’d
 Advantages of water-miscible bases

 able to accommodate large volumes of water

 able to accommodate excess moisture e.g. exudate from abrasions

& wounds.
 Reduced interference with skin function

 easily washed from the skin and from clothing.

 readily applied to (and removed from) hair, skin. Hence High

cosmetic acceptability

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 Water removable bases, cont’d
 Characteristics of water removable bases
 Resemble creams in their appearance
 May be diluted with water or with aqueous solution
 Certain medicinal agents may be better absorbed in the skin
 Water washable
 Contains water
 Can absorb water
 Non-occlusive
 Non-greasy

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 Water-soluble bases
 Completely water-soluble bases have been developed from

the Macrogols (Polyethylene glycols), a range of compounds

with the general formula:-

CH2OH.(CH2OCH2 )n.CH2OH

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 Water-soluble bases, cont’d
 Polyethylene glycols are polymers of ethylene oxide and
water Polycondensation
C2H4O + H2O Poyethylene glycol (Macrogol )
 The chain length may be varied to achieve polymers having
desired viscosity and physical form
 Macrogols 200,300 ,400 - Viscous liquids, Macrogol 1500 -
Semisolids, Macrogols 6000 - waxy solids
 Example: PEG ointment, NF
- PEG 3350 ………400 g
-PEG 400 ………. 600 g

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 Water-soluble bases, cont’d
 Advantages of water- soluble bases

 Water solubility

 Easily removal from the skin

 Readily miscible with tissue exudates

 Good absorption by the skin

 valuable when drugs are required to penetrate the skin

 Good solvent properties – For some water soluble dermatological

e.g. Hydrocortisone

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 water-soluble bases, Advantages,
cont’d
 Freedom from greasiness

 Satisfactory ageing properties

 They don’t hydrolyze, rancidity or support microbial growth

 Compatibility with many dermatological medicaments e.g. -

Ammoniated mercury -Yellow mercuric oxide

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 Disadvantages of water-soluble bases
 Less bland than paraffins, possibly due to their hygroscopic

nature.

 Reduction in activity of certain antimicrobial agents, due to

hydrolysis

 Solvent action on polythene and bakelite; these plastics

should not be used in containers or closures for macrogol

ointments

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 Disadvantages
 Inability to incorporate large volumes of aqueous solutions b/c
 Ointments will soften or
 dissolve the ointment base if the concentration of water is large
enough.
 Its use is usually reserved for the incorporation of solid
therapeutic agents.
 It may incorporate up to 25% of an aqueous solution if a portion
of the lower-molecular-weight polyethylene glycol is replaced
with stearyl alcohol.
 This enhance the mechanical properties of the ointment.

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 Properties of water-soluble bases
 Water soluble and washable
 Non-greasy
 Non/less occlusive
 Lipid free
 Synthetic base
 Relatively inert
 Does not support mold growth
 Little hydrolysis, stable

75
76
77
 Miscellaneous excipients
Miscellaneous excipients: of ointments and pastes

 the therapeutic agent may be added as a solid component

 In absorption and water-miscible bases, the addition may be in the

form of a solution.

 This solution may be aqueous, alcoholic (e.g. propylene glycol,

glycerol) or hydroalcoholic
 must not adversely affect the physical stability and/or the appearance

78
 Miscellaneous excipients, cont’d
 Other excipients may be included in ointments and pastes,

including:
(1) additional/alternative solvents;
(2) preservatives; and
(3) antioxidants.

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 Miscellaneous excipients, cont’d
Additional/alternative solvents

 Are hydrophobic liquid components that may be added to

ointment bases (predominantly hydrophobic or absorption bases).

 Examples of these include:

(1) liquid silicone;

(2) vegetable oils; and
(3) organic esters

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 Miscellaneous excipients, cont’d
Liquid silicone (polydimethylsiloxane)
 used in barrier ointments (water-repellent properties ) to protect
the skin against water-soluble irritants
Vegetable oils
 used to replace mineral oils

 added to hydrophobic or absorption bases to increase the

emollient properties.

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 Miscellaneous excipients, cont’d
Disadvantages: Prone to oxidation requiring the inclusion of
antioxidants, stabilizers which may cause sensitization in some
patients.
E.g. coconut oil, arachis oil, ……

Polar organic solvents

 used to disperse small quantities of active medicament though a
relatively large quantity of ointment base.

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 Miscellaneous excipients, cont’d
Organic esters
 used to replace a mineral oil to enhance the spreadability

 to enhance drug dissolution within the ointment base.

 more consistent in composition than the vegetable oils and are

more resistant to oxidation.

Eg. isopropyl myristate (most commonly used)

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 Miscellaneous excipients, cont’d
 Antioxidants

 The antioxidants that are used in ointment bases are similar to

those listed for emulsion
• Butylated hydroxyanisole BHA))
• ,Butylated hydroxytolnene (BHT),
• ethyl,propyl or dodecyl gallates.
 Chelating agents such as ethylendiaminetetra-acetic acid
(EDTA) may also be used.

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 Miscellaneous excipients, cont’d
 Preservatives

 Preservative may not be required in anhydrous ointments

because the substrate is generally unfavorable to the

multiplication of any contaminating micro-organisms.
 Ointment with an aqueous component requires effective

antimicrobial agents to prevent the growth of organisms that

may cause spoilage and pathogenecity.

85
 Miscellaneous excipients, cont’d
 The preservative for emulsions are also suitable for hydrous

ointment bases.

 Those used most commonly are mixtures of

hydroxybenzoate esters, sorbic acid, phenethyl alcohol,

organic mercurials and quaternary ammonium compounds.

 The effectiveness of the preservative system should be

established by challenge tests with appropriate organisms

86
 Method of preparation
 A well-made ointment is:-
a). Uniform throughout, i.e. it contains
no lumps of separated high melting pt
ingredient of the base.
b). Free from grittiness, insoluble powders
are finely subdivided and large clumps of
particles are absent.
 Methods of preparation must try to satisfy these
criteria.

87
 Method of preparation, cont’d
 Both an a large and a small scale, ointments are prepared by two
general methods.
 Incorporation
 Fusion

 The method for particular preparation depends primarily up on

the nature of ingredients.

88
 Method of preparation, cont’d
I. Incorporation method

In the incorporation method the component of the

ointment are mixed together by various means until a

uniform preparation has been attained.

Before incorporation the ingredient should have the

finest state.

89
 Method of preparation, Incorporation method…
 On a small scale, as in the extemporaneous cpding of Rx:

 Mortal and pestle

 Ointment tile (Slab) and spatula : are a large glass or porcelain plate

may be used to rub the ingredients together.

90
 Method of preparation, Incorporation method…
 Mortar and Pestle
 Used:
1. when large quantities of
liquids are to be
incorporated.

[Link] large quantity of

ointment is to be prepared

91
 Method of preparation, Incorporation method…

 Otherwise, tile and spatula

is satisfactory due to its
large
surface area.

 On a large scale
manufactured
in stainless steel tank.

92
 Method of preparation, Incorporation method…
1. Incorporation of solids
 When preparing an ointment by spatulation, the pharmacist
generally works the ointment with a stainless steel spatula
with a long, broad blade and periodically removes the
accumulation of ointment on the larger spatula with a smaller
spatula.
 If the component of an ointment are reactive with the metal
of the spatula (eg, phenol), hard rubber spatula may be used.

93
 Method of preparation, Incorporation of solids…
 The ointment is prepared by thoroughly rubbing and working

the component together on the hard surface with the spatula

until the product is smooth and uniform.

 Generally the ointment base is placed on one side of the

working surface, and the powdered components, previously

reduced to fine powders and thoroughly blended in the
mortar, area placed on the other.

94
 Method of preparation, Incorporation of solids…
Then a portion of powder is mixed with a portion of the
base until uniform, and the process is repeated until all
portions of the powder and base are combined.
The portions of prepared ointment are then combined
and thoroughly blended by continuous & movement of
the spatula and through the combined portions of
ointment.

95
 Method of preparation, Incorporation of solids…
 When only a small portion of powder is to be added, it may

be added in its entirely to a small portion of ointment base.

 If the quantity of active ingredient is very small you have to

use levigating agent (mineral oil, and glycerin)

 After levigation, the dispersion is incorporated with the

remainder of the base by spatulation or by using the mortar

and pestle

96
 Method of preparation…
2. Incorporation of liquids

Any liquids ingredients should be incorporated at the

end of levigation.

Generally, mortar and pestle is preferred when large

volumes of liquid are added than an ointment slab.

97
 Fusion method of preparation
 All or some of the components of an ointment are
combined by being melted together and cooled with
constant stirring until congested
 When ointment base contains several ingredients of
different melting point; first add constituent of high
melting point and then adding in descending order of
melting point.

98
 Fusion method…
 Advantages of melting in descending order of melting point:

Quicker
Require less heat
Avoid over heating of easily melted
constituent.

99
 Fusion method…
Those components not melted are generally added to the
congealing mixture as its is being cooled and stirred.

Naturally, heat-labile substances and any volatile

components are added last when the temperature of the
mixture is low enough not to cause decomposition and
volatilization of the component.

100
 Fusion method…
Many substances are added to the congealing mixture in
solution, others are added as insoluble powders generally
levigated with a portion of the base.
On a small scale; the fusion process may be conducted in
a porcelain dish or glass beaker
On a large scale; it is generally carried out in large
steam-jacketed kittles.

101
 Fusion method…
Once congealed, the ointment may be passed through:
 an ointment mill (in large-scale manufacture)

 rubbed with a spatula or in a mortar (in small scale ppn) to ensure a uniform

texture.

Many medicated ointments and ointment bases containing such

components as beeswax, hard paraffin, stearyl alcohol, and high
molecular weight polyethylene glycols, which do not tend themselves
well to mixture by incorporation, are prepared by fusion.

102
 Fusion method…
After melting; the melted ointment base should be stirred taking
care, not to cause localized cooling of high melting ointment
constituents .

Localized cooling can be occurred due to:-

 Cold spatula or stirrer

 Putting the dish on cold surface

 Transferring melted base to cold dish

103
 Fusion method…
If the product is granular after cooling, it has to be remelted with
minimum amount of heat and stirred gently until it sets fully.

We use fusion method when:-

 Constituents are with hard consistency (high

melting point components).

 The medicaments is soluble in melted base.

104
 Difficulties encountered in preparation of ointment
Danger of chemical reaction between steel spatula and
some reactive ingredients.
Ex. I2 , salicylic acid, Benzoic acid………
Solution :- to minimize this problem, use bone spatula,
wooden spatula or hard rubber spatula.
 Incorporation of aqueous solution in to hydrocarbon
base.
Solution: addition of wool fat.
 Incorporation of antibiotics sensitive to hydrolysis
Solution:- use hydrocarbon base.

105
 Packaging and storage of ointment
 Ointments are usually packaged either:-
 Jars
 Tubes
Jars : - May be made of glass,
uncolored, dark green,
amber, or blue
 Or made of plastic, or porcelain.

106
 Packaging and storage of ointment…
Tubes:- are made of tin or
of plastic (collapsible tube)

107
 Packaging and storage of ointment…
 Ointment jars may be filled on a small scale by packaging the

weighed amount of ointment in to the jar by means of a

flexible spatula and forcing the ointment down and along the
sides of the jar to avoid the entrapment of air.

 Ointments prepared by fusion may be poured directly in to

the ointment jars for congealing with in the jar. These oints.
normally assume a finished look

108
 Packaging and storage of ointment…
In the large-scale manufacture of ointments, pressure

fillers force a specified amount of an oint in to a jar.

Tubes are generally filled by pressure fillers from the

open back and (opposite and from the cap end) of the
tube which is then closed and sealed.

109
 Packaging and storage of ointment…
 Tube-filled ointment predominate over jar-filled ointments

primarily b/s they are more convenient for the patient.

 Ointments in tubes are less exposed to air and to potential

contaminants and are therefore likely to be more stable

 remain efficacious for longer periods of time

 Most oints must be stored at temperature below 300c to prevent

the softening and liquefying.

110
 2. pastes
 Pastes, like ointments, are intended for external application to the
skin.
 They differ from ointments primarily in that they containing large
proportion of solid materials
 as a consequence are thicker and stiffer than ointment.
 Pastes are used principally as
 absorbents,
 antiseptics
 protective, or to soothe broken skin surfaces,

111
 Pastes…
 They are emollient but, because of the powder content,
porous, hence, perspiration can escape.
 The powder absorb exudates, less macerating than
ointments with similar base.
 Are less greasy than ointments because of the absorption
of the fluid hydrocarbon fraction to the insoluble
particles.

112
 Pastes…
 Most are unsuitable for treating scalp conditions because

they are difficult to remove from the hair.

 Because of the stiffness and absorptive qualities of pastes, they

remain in place after application with little tendency to softer and

flow
 therefore effectively employed to absorb secretion from the site of

application.

113
 Pastes…
 Pastes are therefore preferred for acute lesions that have a

tendency toward crusting, or oozing.

 The film formed on application is opaque and thus can often serve

as a sun-block.

 Pastes are prepared similarly to ointments.

 However, when a levigating agents is to be used to render the

powdered component smooth, a portion of the base is often used

rather than a liquid like mineral oil

114
 Pastes…
 Among the few pastes in use today is zinc oxide paste (Lassar’s

Plain Zinc Paste),

 prepared by levigating and then mixing 25% each of zinc

oxide and starch and calamine with white petrolatum.

 The product is very firm and is better able to protect the skin and

absorb secretions than is zinc oxide ointment

115
 Zinc oxide paste, USP
o Zinc oxide 25.0%
o Starch 25.0%
o Calamine 5.0%
o White petrolatum q.s. 100%
Procedure:
 Titrate the calamine with the zinc oxide and starch and incorporate uniformly
in the petrolatum by levigation in a mortar or on a glass slab with a spatula.
 Mineral oil should not be used as a levigating agent,
 A portion of petrolatum can be melted and used as a levigating agent if so
desired.

116
 Creams
 The term ‘cream’ in pharmacy and medicine is applied to viscous

emulsion or semi-solid emulsion preparation consisting of

solutions or dispersions of one or more medicaments in suitable
base and intended for application to the skin or mucous
membrane.

 The term cream is widely used in pharmaceutical and cosmetic

industry.

117
 Creams …
Many patients and physicians prefer creams to ointments.

 they are generally easier to spread, and, in the case of cream of

the oil-in-water emulsion.

 Easier to remove than many ointments

 They are applied to the skin for:-

 Protective

 Beatifying

 Therapeutic or prophylactic purposes

118
 Creams …
 Creams may contain suitable antimicrobial or preservatives unless
the medicaments or basis have sufficient intrinsic bactericidal and
fungicidal activity
 Creams are mainly two types:-

1). Water- in –oil (W/O) - oily cream

2). Oil –in-water (O/W) - aqueous cream
 O/W emulsions are most useful as water-washable bases, whereas
w/o emulsions are emollient and cleansing.

119
 Creams …
 Patients often prefer O/W b/s

 Cream spreads more readily.

 Is less greasy

 Evaporating water soothes the inflamed tissue.

120
 Creams …
 O/W (vanishing cream) After application of the cream the

water evaporates leaving behind a thin residue film of the stearic

acid.
 For oozing or weeping surface (wound that release exudates from skin) =

b/s O/W mix oozing surface.

 Vanishing cream is prepared by incorporation of significant

amount of stearic acid in an oil-in-water emulsion.

121
 Creams …
Sodium or potassium hydroxide reacts with the stearic

acid to form a soap emulsifier.

Humectants (glycerin, PEG, 7% sorbitol) are

frequently added to vanishing creams and O/W
emulsions to decrease evaporation of water from the
surface of the base.

122
 General compounding procedure for creams
 Emulsified creams are prepared by heating the
components of the oily phase until molten and then
cooling to 600c .
 The component of the aqueous phase are mixed in a
separate vessel and also heated to 600c.
 The aqueous phase is then added to the oily phase at the
same temperature.

123
 General compounding of creams…
 This is important and a thermometer should be used.

 The resulting emulsion should be stirred until cool .

 Rapid cooling may result in separation of high melting point

components.

 Excessive aeration caused by vigorous stirring may also lead to a

granular product.

124
 General compounding of creams…
 If necessary the product may be homogenized after

cooling.

 Creams may contain one or more medicaments in

solution in one or other of the phases.

 Finally powdered insoluble medicaments may be

dispensed in a cream base

125
 Container of Creams
 Wide-mounthed squat jars may be used for creams
where the risk of contamination in use is considered to
be minimal, e.g. Oils creams.
 The container must be well closed and prevent water
evaporation.
 The mouth of the jar should be covered with a disc of
grease proof paper.

126
 Container of Creams…
 Collapsible metal or flexible plastic tubes are to

be preferred since these reduce the risk of contamination

in use and most proprietary products are packed in
tubes.

127
 Gels (gelies)
 Gels are transparent or translucent semi-solid or solid
preparations, consisting of solutions or dispersions of
one or more active ingredients in suitable hydrophilic or
hydrophobic bases.
 Semisolid preparations that contain small inorganic
particles or large organic molecules interpenetrated by a
liquid.

128
 Gels (gelies)…
 Gels made of inorganic materials are usually two - phase
systems where small discrete particles are dispersed
throughout the dispersion medium.
 When the particle size of the dispersed phase is larger, they
are referred to as magmas.
 Gels made of organic molecules are single - phase systems,
where no apparent physical boundary is seen between the
dispersed phase and the dispersion medium.

129
 Gels (gelies)…
The dispersion medium:
 aqueous

 Hydroalcoholic or oleaginous base

 Gels are attractive delivery systems:

 simple to manufacture

 suitable for administering drugs through skin, oral, buccal, ophthalmic, nasal,
otic, and vaginal routes
 provide intimate contact between the drug and

the site of action or absorption.

130
 Gels (gelies)…
 Gels exhibit different physical properties, namely,
imbibition, swelling, syneresis, and thixotropy
 Thixotropy: non -Newtonian flow nature of gels,
which is characterized by a reversible gel - to – sol
formation with no change in volume or temperature
 Imbibition- is the taking up of a certain amount of
liquid by a gel without a measurable increase in volume.

131
 Gels (gelies)…
 Swelling-is the taking up of a liquid by a gel with an
increase in volume.
 Syneresis-Syneresis refers to the contraction or
shrinkage of gels as a result of squeezing out of
dispersion medium from the gel matrix.
 Syneresis is a form of instability in aqueous and non
aqueous gels

132
 Classification and Types of Gels
Classification based on the chemical nature

1. Inorganic hydrogels -are usually two phase systems

such as aluminum hydroxide gel

2. Organic Gels -are usually single phase systems and may

include such gelling agents as Carbomer and Tragacanth

and those that contain an organic liquid, such Plastibase.

133
 Classification and Types of Gels
 Gels are also classified as hydrogels and organogels based on the

physical properties of the gelling agent in the dispersion.

1. Hydrogels: prepared with water - soluble materials or water -

dispersible colloids.
Eg. Natural and synthetic gums such as tragacanth, sodium alginate, and pectin
 inorganic materials: alumina, bentonite, silica, and veegum
 organic materials such as cellulose polymers

134
 Classification and Types of Gels
Organogels (oleaginous gels): prepared using water - insoluble
oleaginous materials
• Prepared using water - insoluble lipids such as glycerol esters of

fatty acids, which swell in water

Eg. Glycerol monooleate, glycerol monopalmito stearete, and

glycerol monolinoleate

 Allows incorporation of both hydrophilic and lipophilic drugs.

135
 Components in gel formulation
Gelling agent

Gelling agent causes thickening

 are either organic hydrocolloids or hydrophilic inorganic
substance.
 They are water dispersible, possess swelling properties, and
improve the viscosity of dispersions

136
 Components in gel formulation …
An ideal gelling agent
 Not interact with other formulation components
 Be free from microbial attack.
 Changes in the temperature and pH during pps and
preservation should not alter its rheological properties.
 Economic
 Readily available
 Colorless gels,
 provide cooling sensation on the site of application, and
possess a pleasant odor.

137
 Examples of Gelling Agents
1. Acacia 13. Cetostearyl Alcohol
2. Bentonite 14. Ethylcellulose
3. Carboxymethylcellulose Na 15. Guar gum
4. Colloidal silicon dioxid 16. Hydroxypropryl cellulose
5. Gelatin 17. Magnesium Al silicate
6. Hydroxyethylcellulose 18. Methylcellulose
[Link] 19. Povidone
8. Maltodextrin 20. Sodium alginate
9. Polyvinyl alcohol 21. Sodium starch glycolat
10. Propylene carbonate 22. Starch
11. Alginic acid 23. Tragacanth
12. Carbomer 24. Xanthan gum

138
 Components in gel formulation …
 Preservatives

 Methylhydroxybenzoate

 Propylhydroxybenzoate

 Hygroscopic agents ( Humectant)

 Eg. Glycerol, propylene glycol or sorbitol solution.

 Chelating agents

 For ingredients which are sensitive to heavy metals. eg. EDTA.

139
 Components in gel formulation
Flavours/sweetening agents
 Included in pharmaceutical gels that are designed for
administration into the oral cavity
e.g. for the treatment of infection, inflammation or ulceration.
Buffers
 As in other pharmaceutical formulations, buffers (e.g. phosphate,
citrate) may be included in aqueous& hydroalcoholic-based gels
Colorants

140
 Magmas
 Are aqueous suspensions of insoluble, inorganic drugs

and differ from gels mainly in that the suspended

particles are larger.

 When prepared, they are thick and viscous, so no need

of a suspending agent.

141
 Preparation of Gels and Magmas
 Generally, the water soluble components are initially dissolved in

the vehicle in a mixing vessel with stirring.

 The hydrophilic polymer must be added to the stirred mixture

slowly to prevent aggregation then continuing stirring until

dissolution of the polymer
 excessive stirring of pharmaceutical gels results in entrapment of air.

 Therefore, to prevent this the mixing rate must not be excessive

142
 Preparation of Gels and Magmas
 By freshly precipitating the disperse phase (chemical rxn)
 The desired gelatinous precipitate results when solutions of
inorganic agents react to form an insoluble chemical having a
high attraction for water.

 Eg: Milk of magnesia is a preparation containing 7 to 8.5%

magnesium hydroxide.

143
 Preparation of Gels and Magmas
 It may be prepared by a reaction between sodium
hydroxide and magnesium sulfate.
2NaOH + MgSO4 Mg(OH)2 + Na2SO4

 By direct hydration of inorganic chemical in water.

Example: Hydration of Magnesium oxide
MgO + H2O Mg(OH)2

144
 Gels (gelies)….
 Use: for medication, lubrication and some miscellaneous
application
 Medicated Jellies
 Jellies contain a considerable amount of water and are particularly
suitable as vehicle for water–soluble medicaments such as local
anesthetics, spermicides, and antiseptics.
 Lubricants Jellies
 Lubricants for - glove
 Miscellaneous jellies
 Patch testing : As a vehicle for allergens applied to the skin to detect
sensitivity

145
 Examples of Magmas and Gels
Bentonite Magma NF suspending agent
Sodium Fluoride and Phosphoric Acid USP dental care prophylactic
Gel
Fluocinonide Gel USP Anti-inflammatory corticosteroid
Tretinoin Gel USP treatment for acne
Erythromycin and Benzoyl peroxide Gel

Clindamycin Topical Gel

Hydroquinone Gel Hyperpigmented skin

Salicylic acid Gel keratolytic

Desoximethasone Gel anti-inflammatory and antipruritic

Aluminum Phosphate Gel USP antacid

(Amphogel)
Aluminum hydroxide Gel USP antacid
Dihydroxyaluminum Aminoacetate USP antacid
Magma
146 Milk of Magnesia (Magnesia Magma) USP Antacid; laxative
 Containers
Containers should be well-filled, to minimize
evaporation of water into the air space, well closed and
stored in a cool place, to prevent drying out.

147