Semi Solids

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SEMISEMISOLIDSSOLIDS

VENUVENUMADHAVMADHAV


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Semisolid pharmaceutical systems comprise a body of products, which when

applied to the skin or accessible mucous membranes tend to alleviate or treat

a pathological condition or offer protection against a harmful environment.

Property to cling to the skin or mucous membrane for a protracted period of

time.

Adhesion is due to their plastic rheologic behavior which allows semisolid to

retain their shape and cling as film until acted upon by an outside force.

Semisolid dosage forms usually are intended for localized drug delivery. In thepast few years, however, these forms also have been explored for the

systemic delivery of various drugs.

Can be applied topically to the skin, cornea, rectal tissue, nasal mucosa,

vagina, buccal tissue, urethral membrane, and external ear lining.

Introduction


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DEFINITION

Semisolid dosage forms are dermatological products of semisolid

consistency and applied to skin for therapeutic or protective action or

cosmetic function.

IDEAL PROPERTIES OF SEMISOLIDDOSAGEFORMS

Physical properties

Smooth texture

Elegant in appearance

Non dehydrating

Non gritty

Non greasy and non staining

Non hygroscopic


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Physiological properties

Non irritating

Do not alter membrane / skin functioning

Miscible with skin secretion

Have low sensitization index

Application properties

Easily applicable with efficient drug release.

High aqueous washability


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Storage properties

Stable under various real world storage conditions as per ICH guidelines.

Storage of semisolids should be at temperatures not exceeding 25C unless

otherwise authorized.

They should not be allowed to freeze and must be stored in a well-closed

container or, if the preparation contains water or other volatile ingredients,

store in an air-tight container.

The containers are preferably collapsible metal tubes from which the

preparation may be readily extruded. If the preparation is sterile, store in a

sterile, airtight, tamper-proof container.


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Climatic

zones

Definition Storage/test

conditions

I Temp. climate 21C + 2C

45% RH + 5% RH

II Mediterranean & subtropical

climate

25C + 2 C

60% RH + 5% RH

III Hot dry climate 30C + 2C

35% RH + 5% RH

IV Hot, humid climate 30C + 2C

75% RH + 5% RH

Types of Climatic Zones


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Types of Semisolid Dosage Forms

OINTMENTS

Soft hydrocarbon based semisolid preparation, composed of fluid

hydrocarbon meshed in a matrix of higher melting solid hydrocarbon

petrolatum being a tasteless, odorless, unctuous material with a melting

range.

Principle ingredients forming the system hydrocarbon and silicon oil are

generally poor solvent for most drugs, seemingly setting a low limit on the

drug delivery capabilities of the system.

CREAMS

Viscous semisolid emulsion system with opaque appearance as contrasted

with translucent ointments. Consistency and rheological character depends

on whether the cream is w/o or o/w.


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Properly designed O/W creams are elegant drug delivery systems, pleasing

in both appearance and feel post application, non greasy and are rinsable.

Good for most topical purpose and are considered particularly for

application to oozing wounds.

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 through

direct interactions of the dispersed particulates and by adsorbing the liquid

hydrocarbon fraction the vehicle on the particle surface.

Pastes are usually prepared by incorporating solids directly into a

congealed system by levigation with a portion of the base to form a paste

like mass.


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Pastes are less penetrating and less macerating and less heating than

ointment.

Good protective barrier when placed on the skin for, in addition to formingan unbroken film, the solid they contain can absorb and thereby neutralize

certain noxious chemicals before they ever reach the skin, an effective sun

block accordingly.

Skiers apply paste around the nose and lips to gain a dual protection.

Pastes are less greasy because of the absorption of the fluid hydrocarbon

fraction to the particulates.

GELS (JELLIES)

Gels are semisolid system in which a liquid phase is constrained within a

3-D polymeric matrix (consisting of natural or synthetic gum) having a high

degree of physical or chemical cross-linking.


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Gels are aqueous colloidal suspensions of the hydrated forms of insoluble

medicament.

Jellies are transparent or translucent non-greasy semisolid gels.

Used for medication, lubrication.

POULTICES

Soft, viscous, pasty preparation for external use.

Applied to skin while they are hot. Poultice must retain heat for a considerable

time because they are intended to supply warmth to inflamed parts of body.

e.g. Kaolin poultice (B.P.C.)

PLASTERS

RIGID 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, aerosolized shaving creams


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FACTORS AFFECTINGSKIN PENETRATION

The principle physicochemical factor in skin penetration is the hydration

state of stratum corneum, which affects the rate of passage of all

substances that penetrate the skin.

The temperature of skin and the concentration of the drug play significant

roles, but they are secondary to that of hydration.

The solubility of a drug determines the concentration presented to the

absorption site, the water or lipid partition coefficient influences the rate of

transport.

An inverse relationship appears to exist between the absorption rate and

the molecular weight. Small molecules penetrate more rapidly than large

molecules, but within a narrow range of molecular size, there is little

correlation between the size and the penetration rate.


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1. BASES

2. HYDROCARBONWAXES

3. OLEOGENOUSSUBSTANCES

4. FATTY ACIDS & ALCOHOLS

5. EMULCIFIERS

6. POLYOLS

7. INSOLUBLE POWDERS

8. FRAGRANCES

9. ANTIOXIDANTS

10. PRESERVATIVES

11. CHELATING AGENTS

12. HUMECTANTS

Formulation of Semisolid Dosage Forms


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1. BASES

An ointment base should be compatible with skin, stable, smooth and

pliable, non-irritating, non-sensitizing, inert, capable of absorbing water

or other liquid preparations, and of releasing the incorporated

medicament, readily.

A base for ophthalmic ointments must be non-irritating to the eye, should

permit the diffusion of the drug and should retain the activity of the

medicament for a reasonable period often under proper storage

conditions. It should also be sterilizable conveniently.

A)Oleaginous orHydrocarbon bases

Combination of more than one oleaginous material such as water-insoluble hydrophobic oils and fats.

Combinations of these materials can produce a wide range of meltingpoints and viscosities.

e.g. Petrolatum and White ointment (Petrolatum with 5% beeswax)


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Commonly used petrolatum consistency, bland, neutral, spread easily

difficult to wash, occlusive covering

B)Absorption (Emulsifiable)Bases

Formed by addition of substances miscible with hydrocarbons & posses

polar group sulfate, sulfonate, carboxyl, hydroxyl, ether

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 W/O type emulsions and have capacity to absorb

considerable quantities of water or aqueous solution without marked changes

in consistency.

e.g. Lanolin, Lanolin isolates, Cholesterol, Lanosterol, Acetylated alcohols or

partial esters of polyhydric alcohols (sorbitan mono stearate or mono

laurate)added to make hydrocarbon bases hydrophilic.


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Do not absorb moisture , but agitation absorb.

2 types

1. Anhydrous type Lanolin & hydrophilic Petrolatum

2. Emulsion Non ionic emulsifiers Glyseryl mono stearare,

Cholesterol, Cetyl alcohol.

C).Emulsion orWater removable Bases

W/O emulsions are not water-washable as the oil is in the external phase

and O/W emulsions are used in dermatological preparations and cosmetic

creams. Some of the popular creams include cold creams, vanishing

creams. Skin creams, emollient creams, foundation creams, hand creams

etc.

e.g. Stearic acid, Stearyl alcohol, Cetyl alcohol, GMS


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D)WaterSoluble Bases

Both anhydrous and hydrous dermatological non-emulsion bases which are

water soluble and contain no oil phase.e.g. Polyethylene glycols or one or more of the other hydrocolloids.

Polyethylene glycols (Carbowaxes) are water soluble, non-volatile,

unctuous compounds.

Different grade of cabowaxes are available which are designated by anumber approximating their average molecular weights e.g.- 200, 300, 400,

600, 1000, 1540, 4000 and 6000.

At RT, carbowaxes 200 to 400 are clear liquids whereas carbowaxes 1000

to 60000 are white, waxy solids.

A variety of water washable ointment bases with consistencies ranging from

semi-solid to solid can be obtained by blending different polyethylene

glycols. Polyethylene Glycol Ointment USP is a blend of Carbowaxes 4000

and 400.


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Appropriate Selection ofOintment Base

Desired release rate of the drug substance from the ointment base.

Rate and extent of topical or percutaneous drug absorption.

Desirability of occlusion of moisture from skin. Stability of the drug in the ointment base.

Effect of drug on the consistency of base.

Easy removal of base on washing.

Characteristic of the surface to which it is applied.


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2.HYDROCARBONWAXES

Frequently employed in mfr of cream & ointments to increase viscosity

of mineral oil in order to prevent its separation from ointment.

E.g.: Ozokerite M.P. 65-750c consist mixture of hydrocarbons.

Paraffin wax M.P. 35-750c obtained from petrolatum.

Ceresin mixture of ozokerite & paraffin wax.

Synthetic waxes: Developed from veg oils & naturally occurring oils

by process of hydration and catalytic splitting.

Complex mixtures of long chain saturated aliphatic chemical entities.

Exhibit thermoplastic and crystalline properties.


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3.OLEOGENOUSSUBSTANCES

E.g: Veg oils Peanut oil, Almond oil, Sesame oil, Olive oil.

4. FATTY ACIDS & ALCOHOLS

FATTY ACIDS: Stearic acid, Palmitic acid

. Various ratios are used

. Stearic acid used in water removable creams & give matt

appearance to skin

. Stearate soap used enough KOH or Triehanolamine added

ALCOHOLS: Stearyl alcohol & Cetyl alcohol as emulcifiers or

emollients

Stearyl alcohol produce firm cream, Cetyl produce softer


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5.EMULCIFIERS

E.g.: Water soluble soaps

Increase viscosity & stability of o/w type emulsion.

Combination of surfactant & oil soluble emulsifier called mixed

emulsifier. (Triehanolamine stearate soap with cetyl alcohol).

Soap type emulsion is unstable in presence of acidic substances.

- Cationic or non-ionic emulcifiers are preferable for drugs requiring

acid pH (Quaternary ammonium compounds cetyl trimethyl

ammonium chloride help to stabilize these compounds along with

cetyl alcohol).

- Non ionic emulsifiers are used for both o/w & w/o

(Promulgens mixture of fatty acids & their ethoxylates)

Recently chemically bonded lactic acid with fatty acids.

mild & non irritating to skin and eye, produce emollient effect


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6.POLYOLS

Prevent drying of skin, improve consistency and rubout qualities of cream

E.g.: Glycerin, Propylene glycol, Sorbitol(70%).

Sorbitol more hygroscopic than glycerine used at low conc.

PEG & PG occasionally used in combination with glycerine less

moisture absorption.

7.INSOLUBLE POWDERS

8.FRA

GRANCES- Lavender oil, Rose oil, Lemon oil, Almond oil

9. ANTIOXIDANTS

- BHA, BHT, Propyl gallate.


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10. PRESERVATIVES

- Parabens, Chlorocresol, Benzoic acid,

11. CHELATING AGENTS

12.HUMECTANTS

- PEG, Glycerol or Sorbitol


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USEOF PERMEATIONENHANCERSIN FORMULATIONOF

SEMISOLIDDOSAGE FORMS

Skin can act as a barrier and prevent deep penetration of drug molecules.With the introduction of various penetration enhancers, however, systemic

drug delivery through the transdermal route has gained major footing.

Permeation enhancer Drugs used

Menthol, carvacrol, linalool Propranolol hydrochloride

Limonene Indomethacin, ketoprofen

Geraniol, nerolidol Diclofenac sodium

Oleic acid PiroxicamLecithin Hydrocortisone acetate, heparin

Propylene-glycol-

dipelargonate

Heparin

Cyclodextrins Hydrocortisone


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TRITURATIONWhen base contain soft fats and oils or medicament is insoluble and/or

liquid.

FUSION

When soft fats or waxes are to be incorporated with hard fats or waxesthen of this to be melted to get homogenous mixture with stirring.

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.

OINTMENTMILLS

It is used for large scale production where triple roller mill is utilized which

is faster then others.

Methods of preparation


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PACKINGAND LABELING

` Large-mouth jar (glass or plastic)

` Metal (Aluminium) or plastic tubes

`Well closed containers to protect against contamination

` Cool place to protect against product separation by heat

` When requires light resistance or opaque container for light sensitive drugs

` In addition to the usual labeling, the USP directs that for certain ointments and

creams include the type of base used either water soluble or water insoluble


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Quality control ofSemisolid Preparations


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OTHERS

SPREADABILITY

PRESENCEOR ABSENCEOF GRITTY PARTICLES

WASHABILITY

IRRITANCY

STABILITY

Semi Solids

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