Include drug delivery systems and Include drug delivery systems and

dosage forms intended to be applied to dosage forms intended to be applied to

the skin. the skin.

CreamsCreams

OintmentsOintments

GelsGels

PastesPastes

Preparations are applied to the skin for:Preparations are applied to the skin for:

Physical effectsPhysical effects

skin protection, lubricants, emollients, drying agentsskin protection, lubricants, emollients, drying agents

Medical effectsMedical effects

•Treatment of skin conditions (non-systemic topical effect)Treatment of skin conditions (non-systemic topical effect)

as skin infections, itching, burns, diaper rash, insect as skin infections, itching, burns, diaper rash, insect

stings and bites, corns, calluses, warts, dandruff, acne, stings and bites, corns, calluses, warts, dandruff, acne,

psoriasis, and eczema.psoriasis, and eczema.

• Systemic effectSystemic effect

The Skin The Skin

The skin has a wide variety of functions:The skin has a wide variety of functions:

Protect the organism from water loss and Protect the organism from water loss and

mechanical, chemical, microbial, and physical mechanical, chemical, microbial, and physical

influences. influences.

Structure of the SkinStructure of the SkinThe skin is the largest human organ and is composed of:The skin is the largest human organ and is composed of:

A film of emulsified material present upon the surface of A film of emulsified material present upon the surface of

the skin composed of a complex mixture of sebum, sweatthe skin composed of a complex mixture of sebum, sweat

Three functional layers: Three functional layers:

Epidermis, Epidermis,

Dermis (true skin) Dermis (true skin) Hypodermis Hypodermis (Subcutaneous fat layer).(Subcutaneous fat layer).

Blood capillaries and Blood capillaries and

nerve fibersnerve fibers

Sweat glandsSweat glands

Hair folliclesHair follicles

The epidermis is the outermost layer of the skinThe epidermis is the outermost layer of the skin

0.02 to 5 mm thickness 0.02 to 5 mm thickness

It has five layers,It has five layers,

o Barrier layer (stratum germinativum)Barrier layer (stratum germinativum)

Beneath the hornylayerBeneath the hornylayer

Composed of living epidermal cellsComposed of living epidermal cells

o Horny layer Horny layer

(stratum corneum)(stratum corneum)

The uppermost layerThe uppermost layer

Composed of dead epidermal cells forms the permeability barrierComposed of dead epidermal cells forms the permeability barrier

The stratum corneum consists of:The stratum corneum consists of:

Horny skin cells Horny skin cells (corneocytes)(corneocytes) which are connected which are connected

via protein-rich attachments of the cell membranevia protein-rich attachments of the cell membrane

The corneocytes are embedded in a lipid matrix in The corneocytes are embedded in a lipid matrix in

““Brick and mortarBrick and mortar” structure.” structure.

The corneocytes of hydrated keratin comprise the The corneocytes of hydrated keratin comprise the

bricks and the epidermal lipids fill the space bricks and the epidermal lipids fill the space

between the dead cells like mortarbetween the dead cells like mortar

Routes of skin PenetrationRoutes of skin Penetration

Include transport via:Include transport via:

1-1- Hair follicles and sebaceous Hair follicles and sebaceous

glands glands

2-2- Sweat glandsSweat glands

1 2

These routes avoid penetration through the stratum These routes avoid penetration through the stratum

corneum and therefore known as corneum and therefore known as shunt routesshunt routes. .

These routes avoid penetration through the stratum These routes avoid penetration through the stratum

corneum and therefore known as corneum and therefore known as shunt routesshunt routes. .

The Transappendageal route:The Transappendageal route:The Transappendageal route:The Transappendageal route:

There are two diffusional routes to penetrate intact skinThere are two diffusional routes to penetrate intact skin::

1 2

Although these routes offer high permeability, they are of Although these routes offer high permeability, they are of

minor importance because of their relatively small area, minor importance because of their relatively small area,

0.1% of the total skin area. 0.1% of the total skin area.

The transappendageal route The transappendageal route

seems to be most important for seems to be most important for

ions and large polar molecules ions and large polar molecules

which hardly permeate through which hardly permeate through

the stratum corneum.the stratum corneum.

The transappendageal route The transappendageal route

seems to be most important for seems to be most important for

ions and large polar molecules ions and large polar molecules

which hardly permeate through which hardly permeate through

the stratum corneum.the stratum corneum.

Transepidermal transport Transepidermal transport

means that molecules cross means that molecules cross

the intact horny layerthe intact horny layer

The The tra

nsepidermal ro

ute :

transepiderm

al route :

The The tra

nsepidermal ro

ute :

transepiderm

al route :

Two potential micro-routes are existingTwo potential micro-routes are existing

**The transcellular (intracellular) routThe transcellular (intracellular) rout

*The intercellular pathways*The intercellular pathways

The principal pathway taken by The principal pathway taken by

drugs is decided by its partition drugs is decided by its partition

coefficientcoefficient

Hydrophilic drugs partition into the intracellular pathways, Hydrophilic drugs partition into the intracellular pathways,

whereas lipophilic drugs traverse the stratum corneum via whereas lipophilic drugs traverse the stratum corneum via

the intercellular route.the intercellular route.

Factors Affecting Percutaneous AbsorptionFactors Affecting Percutaneous Absorption

Factors concerning the nature of the drug Factors concerning the nature of the drug

Factors concerning the nature of the vehicleFactors concerning the nature of the vehicle

Factors concerning the condition of the skinFactors concerning the condition of the skin

Percutaneous absorptionPercutaneous absorption is the absorption of substances is the absorption of substances

from outside the skin to positions beneath the skin, from outside the skin to positions beneath the skin,

including entrance into the blood stream.including entrance into the blood stream.

1.1. Drug concentration Percutaneous absorption Drug concentration Percutaneous absorption

2.2. Drug partition coefficient (greater attraction to the skin Drug partition coefficient (greater attraction to the skin

than to the vehicle) Percutaneous absorptionthan to the vehicle) Percutaneous absorption

3.3. Molecular weight below 800 Molecular weight below 800

Percutaneous absorptionPercutaneous absorption

4.4. Particle SizeParticle Size

Percutaneous absorptionPercutaneous absorption

5. Solubility in mineral oil and water5. Solubility in mineral oil and water

Percutaneous absorptionPercutaneous absorption

Factors concerning the nature of the drug Factors concerning the nature of the drug

1.1. Spreadability of the vehicle Spreadability of the vehicle

Percutaneous absorptionPercutaneous absorption

2.2. Mixing with the sebum Mixing with the sebum

Percutaneous absorptionPercutaneous absorption

3.3. Hydration of the skin Percutaneous absorption Hydration of the skin Percutaneous absorption

Oleaginous vehicles act as moisture barriers through Oleaginous vehicles act as moisture barriers through

which the sweat from the skin cannot pass, thus which the sweat from the skin cannot pass, thus

increased hydration of the skin beneath the vehicle and increased hydration of the skin beneath the vehicle and

increase Percutaneous absorption.increase Percutaneous absorption.

Factors concerning the nature of the vehicleFactors concerning the nature of the vehicle

Factors concerning the condition of the skinFactors concerning the condition of the skin

Transdermal absorption follow Transdermal absorption follow Fick’s First LawFick’s First Law of of DiffusionDiffusion

Js = Js = Km D CsKm D Cs

EE

Js = Flux of solute through the skinJs = Flux of solute through the skin

Km = Distribution coefficient of drug between Km = Distribution coefficient of drug between vehicle and vehicle and

stratum corneumstratum corneum

Cs = Concentration difference of solute across the Cs = Concentration difference of solute across the

membranemembrane

D = Membrane Diffusion coefficient for drug in D = Membrane Diffusion coefficient for drug in stratum stratum

corneumcorneum

E = Thickness of stratum corneum E = Thickness of stratum corneum

1.1. The thickness stratum corneum The thickness stratum corneum

Percutaneous absorptionPercutaneous absorption

2.2. Multiple application dosing Multiple application dosing

Percutaneous absorption than single Application Percutaneous absorption than single Application

3.3. Time of contact with the skin Time of contact with the skin

Percutaneous Percutaneous

absorptionabsorption

4.4. Broken skin permit (remove of the stratum corneum) Broken skin permit (remove of the stratum corneum)

Percutaneous absorptionPercutaneous absorption

Percutaneous Absorption Enhancers

Mechanisms of action by which Materials enhance Mechanisms of action by which Materials enhance

absorption through stratum corneum is either by absorption through stratum corneum is either by

Enhancing drug release from the formulation to the skinEnhancing drug release from the formulation to the skin

Reduction of the resistance of the stratum corneum by Reduction of the resistance of the stratum corneum by

altering it physicochemical propertiesaltering it physicochemical properties

Alteration of the hydration of the stratum Alteration of the hydration of the stratum

corneum using occlusive formulationscorneum using occlusive formulations

Carrier mechanisms in the transport of ionisable Carrier mechanisms in the transport of ionisable

drugsdrugs

Enhance absorption by directly Enhance absorption by directly

influencing influencing

the stratum corneum the stratum corneum

(CHEMICALLY or PHYSICALLY)(CHEMICALLY or PHYSICALLY)

This can be achieved by the following This can be achieved by the following mechanisms:mechanisms:

Chemicals used to enhance absorption by directly Chemicals used to enhance absorption by directly

influencing the stratum corneuminfluencing the stratum corneum

Chemicals interact with the Chemicals interact with the keratin structurekeratin structure in the stratum in the stratum

corneum and open the tight protein structure, this leads corneum and open the tight protein structure, this leads

increase the diffusion coefficient D for substances which use increase the diffusion coefficient D for substances which use

the transcellular route: the transcellular route:

Surfactants, Dimethylsulfoxide (DMSO)Surfactants, Dimethylsulfoxide (DMSO) and Urea

Solvents extract lipids and making the stratum corneum more Solvents extract lipids and making the stratum corneum more

permeable: permeable: Dimethylsulfoxide (DMSO) and EthanolDimethylsulfoxide (DMSO) and Ethanol

Chemical enhancersChemical enhancers which intercalate into the structured which intercalate into the structured

lipids of the horny layer and disrupt the packing. Thus lipids of the horny layer and disrupt the packing. Thus

make the regular structure more fluid and increases the make the regular structure more fluid and increases the

diffusion coefficient of drugs: diffusion coefficient of drugs:

Azone, Oleic acid, and isopropyl myristateAzone, Oleic acid, and isopropyl myristate

Solvents increase solubility and improve partitioning:Solvents increase solubility and improve partitioning:

Alcohol, acetone, polyethylene and propylene glycolAlcohol, acetone, polyethylene and propylene glycol

Ointments are semisolid preparations intended for Ointments are semisolid preparations intended for

external application. external application.

Ointments may be medicated or non-medicated Ointments may be medicated or non-medicated

Non-medicatedNon-medicated ointment bases used for their ointment bases used for their

emollient, lubricating effect or as vehicles in the emollient, lubricating effect or as vehicles in the

preparation of preparation of medicated ointmentsmedicated ointments

Ointment bases are classified into 4 groups: Ointment bases are classified into 4 groups:

(1)(1) Hydrocarbon bases (Oleaginous Base)Hydrocarbon bases (Oleaginous Base)

(2)(2) Absorption bases Absorption bases

(3)(3) Water-removable basesWater-removable bases

(4)(4) Water soluble basesWater soluble bases

Ointment BasesOintment Bases

1.1. Water-free Water-free

2.2. Difficult to wash offDifficult to wash off

3.3. Aqueous preparations are difficult to be Aqueous preparations are difficult to be

incorporated into themincorporated into them

4.4. Used as occlusive dressings for their emollient effect Used as occlusive dressings for their emollient effect

(helps the skin retain moisture) (helps the skin retain moisture)

It can treat diaper rash (protect skin It can treat diaper rash (protect skin

from from

urine) and dry skin (retain moisture) urine) and dry skin (retain moisture)

5.5. Stable, don’t dry upon agingStable, don’t dry upon aging

Hydrocarbon bases (oleaginous bases)Hydrocarbon bases (oleaginous bases)

Petrolatum (Soft Paraffin)Petrolatum (Soft Paraffin)

Yellow Petrolatum (Vaseline)Yellow Petrolatum (Vaseline)

Mixture of semisolid hydrocarbons obtained from petroleum. Mixture of semisolid hydrocarbons obtained from petroleum.

Melts at temperatures between 38° and 60°CMelts at temperatures between 38° and 60°C

Form an ointment-like gel with Polyethylene (PLASTIBASE) Form an ointment-like gel with Polyethylene (PLASTIBASE)

which is compatible with most medicaments.which is compatible with most medicaments.

White Petrolatum (White Vaseline) White Petrolatum (White Vaseline)

Decolorized petrolatum Decolorized petrolatum

More esthetically acceptable to patients than petrolatum.More esthetically acceptable to patients than petrolatum.

White Ointment (Simple Ointment)White Ointment (Simple Ointment)

Contains 5% of White wax and 95 % of White petrolatumContains 5% of White wax and 95 % of White petrolatum

Contains 5% of yellow wax and 95 % of petrolatum. Contains 5% of yellow wax and 95 % of petrolatum.

Yellow Wax, is the purified wax obtained from the honeyYellow Wax, is the purified wax obtained from the honey

Yellow Ointment (Simple Ointment)Yellow Ointment (Simple Ointment)

Absorption BasesAbsorption Bases

An absorption base is an oleaginous base that permit the An absorption base is an oleaginous base that permit the

incorporation of aqueous solutions, and can be used asincorporation of aqueous solutions, and can be used as

emollients emollients

Like the oleaginous bases,Like the oleaginous bases,

• Absorption bases are not water washableAbsorption bases are not water washable

• They can incorporate 50% of their volume water,They can incorporate 50% of their volume water,

where aqueous solution first incorporated into the where aqueous solution first incorporated into the

absorption base, then added into the oleaginous baseabsorption base, then added into the oleaginous base

2)2) Water-in-oil emulsions (emulsion bases) that permit the Water-in-oil emulsions (emulsion bases) that permit the

incorporation of small, additional quantities of aqueous incorporation of small, additional quantities of aqueous

solutionssolutions

(e.g. Lanolin and Cold cream)(e.g. Lanolin and Cold cream)

There are two types of absorption bases: There are two types of absorption bases:

1)1) Contains a w/o emulsifying agent: Contains a w/o emulsifying agent:

When water is taken up into the base, it will form a When water is taken up into the base, it will form a w/ow/o

emulsionemulsion

(e.g. Hydrophilic Petrolatum and Anhydrous Lanolin)(e.g. Hydrophilic Petrolatum and Anhydrous Lanolin)

It has the ability to absorb It has the ability to absorb

water (upto 3 times its water (upto 3 times its

weight), with formation of weight), with formation of

water-in-oil emulsion W/Owater-in-oil emulsion W/O

Hydrophilic Petrolatum (Aquaphor)Hydrophilic Petrolatum (Aquaphor)

Hydrophilic Petrolatum is composed of 3% cholesterol, Hydrophilic Petrolatum is composed of 3% cholesterol,

3% stearyl alcohol, 8% white wax, and 86% white 3% stearyl alcohol, 8% white wax, and 86% white

petrolatum. petrolatum.

Obtained from the wool of sheepObtained from the wool of sheep

It is a water-in-oil emulsion W/O that contains between It is a water-in-oil emulsion W/O that contains between

25 and 30% water 25 and 30% water Additional water may be incorporated into Additional water may be incorporated into

lanolin by mixinglanolin by mixing

Lanolin (Hydrous Wool Fat)Lanolin (Hydrous Wool Fat)

It is insoluble in water, but mixes It is insoluble in water, but mixes

without separation with water twice without separation with water twice

its weight of water with the its weight of water with the

formation of a water in-oil emulsion formation of a water in-oil emulsion

Anhydrous Lanolin (Wool Fat)Anhydrous Lanolin (Wool Fat)

Oil in Water emulsionsOil in Water emulsions

Have the general formula: 30 % Emulsifying waxHave the general formula: 30 % Emulsifying wax

50 % White soft Paraffin50 % White soft Paraffin

20 % Liquid Paraffin20 % Liquid Paraffin Water washableWater washable

They can be diluted with water or with aqueous They can be diluted with water or with aqueous

solutions. “solutions. “water-lovingwater-loving “ “

They have the ability to absorb serous discharges They have the ability to absorb serous discharges

in dermatologic conditionsin dermatologic conditions

Water-Removable BasesWater-Removable Bases oil-in-water emulsionsoil-in-water emulsions

Methyl and propyl parabens are used as preservativesMethyl and propyl parabens are used as preservatives

Sodium Lauryl SulfateSodium Lauryl Sulfate1 %1 %    emulsifying agentemulsifying agent

Stearyl AlcoholStearyl Alcohol25 %25 % emulsifying agentemulsifying agent

White PetrolatumWhite Petrolatum25 %25 %    oleaginous phase oleaginous phase

Propylene GlycolPropylene Glycol12 %12 %    aqueous phaseaqueous phase

Purified WaterPurified Water37 %37 % aqueous phaseaqueous phase

Hydrophilic OintmentHydrophilic Ointment

Have the general formula:Have the general formula:

Water-Soluble Bases (Water-Soluble Bases (greaseless bases)greaseless bases)Water-Soluble Bases (Water-Soluble Bases (greaseless bases)greaseless bases)

Unlike water-removable basesUnlike water-removable bases, ,

which contain both water-soluble and water-insoluble which contain both water-soluble and water-insoluble

components, water-soluble bases contain only water soluble components, water-soluble bases contain only water soluble

components with the absence of any oleaginous materialscomponents with the absence of any oleaginous materials

Like water-removable basesLike water-removable bases, ,

They are water washableThey are water washable

Because they soften greatly with the addition of water, aqueous Because they soften greatly with the addition of water, aqueous

solutions are not preferred to be incorporated into these bases. solutions are not preferred to be incorporated into these bases.

They are better used for the incorporation of nonaqueous or They are better used for the incorporation of nonaqueous or

solid substancessolid substances

Polyethylene glycols are polymers of ethylene oxide and Polyethylene glycols are polymers of ethylene oxide and

water represented by the formula water represented by the formula

HOCHHOCH22(CH(CH22OCHOCH22)nCH)nCH22OHOH

The chain length varied to achieve polymers with different The chain length varied to achieve polymers with different

physical form (liquid, semisolid, or solid).physical form (liquid, semisolid, or solid).

Polyethylene Glycol OintmentsPolyethylene Glycol Ointments

PEGPEGAPPEARANCE AT 25° C APPEARANCE AT 25° C PHPHAVERAGE AVERAGE

MOLECULAR MOLECULAR WEIGHT WEIGHT

MELTING MELTING POINT POINT

HYDROXYL HYDROXYL VALUEVALUE

MOISTURE MOISTURE CONTENT CONTENT

MAX. MAX.

PEG-200PEG-200Clear viscous colorless Clear viscous colorless liquidliquid4.0-7.04.0-7.0190-210190-210<65°C<65°C500-550500-5501.0%1.0%

PEG-300PEG-300Clear viscous colorless Clear viscous colorless liquidliquid4.0-7.04.0-7.0290-310290-310<15°C<15°C340-394340-3941.0%1.0%

PEG-400PEG-400Clear viscous colorless Clear viscous colorless liquidliquid4.0-7.04.0-7.0390-410390-4104-8°C4-8°C264-300264-3001.0%1.0%

PEG-600PEG-600Clear viscous colorless Clear viscous colorless liquidliquid4.0-7.04.0-7.0590-610590-61015-17°C15-17°C176-200176-2001.0%1.0%

PEG-1000PEG-1000White waxy solidWhite waxy solid4.0-7.04.0-7.0950-1050950-105037-38°C37-38°C105-120105-1201.0%1.0%

PEG-1500PEG-1500White waxy solidWhite waxy solid4.0-7.04.0-7.01450-15501450-155044-45°C44-45°C70-9070-901.0%1.0%

PEG-2000PEG-2000White flakesWhite flakes4.0-7.04.0-7.01950-20501950-205045-46°C45-46°C50-7050-701.0%1.0%

PEG-4000PEG-4000White flakesWhite flakes4.0-7.04.0-7.03800-42003800-420053-56 °C53-56 °C30-3630-361.0%1.0%

PEG-6000PEG-6000White flakesWhite flakes4.0-7.04.0-7.05500-65005500-650055-63 °C55-63 °C16-2016-201.0%1.0%

Preparation of polyethylene glycolPreparation of polyethylene glycol

ointment base:base:

Combine polyethylene glycol 3350 (solid) 40 % Combine polyethylene glycol 3350 (solid) 40 %

and polyethylene glycol 400 (liquid) 60 % and polyethylene glycol 400 (liquid) 60 %

If an aqueous solution is to be incorporated into the base, If an aqueous solution is to be incorporated into the base,

substitution some of polyethylene glycol 3350 with an equal substitution some of polyethylene glycol 3350 with an equal

amount of stearyl alcohol would be advantageous to render amount of stearyl alcohol would be advantageous to render

the final product more firm.the final product more firm.

  

OLEAINOUS OLEAINOUS GG

OINTMENT OINTMENT BASESBASES

ABSORPTION ABSORPTION OINTMENT OINTMENT

BASESBASES

WATER-WATER-REMOVABLEREMOVABLE

OINTMENT BASESOINTMENT BASES

WATER-WATER-SOLUBLE SOLUBLE OINTMENT OINTMENT

BASESBASES

CompositioCompositionn

Oleaginous Oleaginous compoundscompounds

Oleaginous Oleaginous bases +bases +w/o w/o surfactantsurfactant

Oleaginous base + Oleaginous base + Water (> 45%) + Water (> 45%) + O/W surfac. (HLB O/W surfac. (HLB >>9)9)

Polyethylene Polyethylene Glycols Glycols (PEGs)(PEGs)

Water Water ContentContent

AnhydrousAnhydrousanhydrousanhydroushydroushydrousanhydrous, anhydrous, hydroushydrous

Affinity Affinity for Waterfor Water

HydrophobicHydrophobichydrophilichydrophilichydrophilichydrophilichydrophilichydrophilic

SpreadabiliSpreadabilityty

difficultdifficultdifficultdifficulteasyeasymoderate to moderate to easyeasy

WashabilitWashabilityy

non-non-washablewashable

non-non-washablewashable

washablewashablewashablewashable

StabilityStabilityoils poor; oils poor; hydrocarbonhydrocarbons betters better

oils poor; oils poor; hydrocarbons hydrocarbons betterbetter

unstableunstablestablestable

Drug Drug IncorporatIncorporat

ion ion PotentialPotential

Solids Solids Oils (oil Oils (oil soluble soluble drugs)drugs)

SolidsSolidsOilsOilsAqueous Aqueous solutions solutions

Solid Solid Aqueous solutions Aqueous solutions (small amounts)(small amounts)

Solid Solid Aqueous Aqueous solutionssolutionsNon-aqueous Non-aqueous solutionssolutions

Continue Continue 

OLEAGINOUOLEAGINOUSS

OINTMENT OINTMENT BASESBASES

ABSORPTION ABSORPTION OINTMENT BASESOINTMENT BASES

WATER-WATER-REMOVABLEREMOVABLEOINTMENT OINTMENT

BASESBASES

WATER-WATER-SOLUBLE SOLUBLE OINTMENT OINTMENT

BASESBASES

Drug Drug ReleaseRelease

poorpoorpoorpoorbut > oleaginousbut > oleaginous

fair to goodfair to goodgoodgood

OcclusiveneOcclusivenessssyesyesyesyesnononono

UsesUses

ProtectantsProtectantsEmollientsEmollients Vehicles Vehicles for for hydrolysable hydrolysable drugsdrugs

ProtectantsProtectantsEmollients Emollients Vehicles for Vehicles for aqueous aqueous solutions, solutions, solids, solids, and non and non hydrolyzable hydrolyzable drugsdrugs

EmollientsEmollients Vehicles for Vehicles for solid, liquid, or solid, liquid, or non-non-hydrolyzable hydrolyzable drugsdrugs

Drug Drug vehiclesvehicles

ExamplesExamples

Yellow Yellow PetrolatumPetrolatum White White PetrolatumPetrolatum Yellow Yellow Ointment Ointment White White OintmentOintment

Hydrophilic Hydrophilic Petrolatum Petrolatum (Aquaphor®),(Aquaphor®), Anhydrous Anhydrous LanolinLanolin Lanolin Lanolin

Hydrophilic Hydrophilic OintmentOintment

PEG PEG OintmentOintment

Selection of the Appropriate BaseSelection of the Appropriate BaseSelection of the Appropriate BaseSelection of the Appropriate Base

The condition of the patient's skin, e.g. oozing or dryThe condition of the patient's skin, e.g. oozing or dry

The rule in dermatology thatThe rule in dermatology that

if a patient's skin is dry-wet it, If it is wet-dry itif a patient's skin is dry-wet it, If it is wet-dry it

if a patient's skin is dry, occlusive ointment base that retain if a patient's skin is dry, occlusive ointment base that retain

moisture is preferablemoisture is preferable

The selection of the base of an ointment

depends on many factors:

Patient FactorsPatient Factors

Physicochemical FactorsPhysicochemical Factors The desired release rate of the drug from the ointment base

The desired enhancement of the percutaneous absorption

of the drug

The desired occlusion of moisture from the skin by the base

The stability of the drug in the ointment base, for a drug that

hydrolyzes rapidly as antibiotics, a hydrocarbon base would

provide the greatest stability

The influence of the drug on the consistency of the ointment

base

11

22

33

44

55

The influence of the drug on the consistency of the ointment

base

The desired washability of the base as for application to

hairy regions, a Polyethylene Glycol base is preferred

For ophthalmic ointments, non-irritant bases are desired.

Absorption O/W emulsion bases and water soluble bases

are irritants due to the effect of the surfactants in the base

It is preferred to use yellow paraffin but not white due to the

irritation effect of the bleaching agents

88

77

66

Preparation of OintmentsPreparation of Ointments

depending on the nature of the ingredients depending on the nature of the ingredients

ointments are prepared by two methods: ointments are prepared by two methods:

A- INCORPORATION OF SOLIDS:A- INCORPORATION OF SOLIDS:

Using the geometric dilution methodUsing the geometric dilution method

The powdered components reduced to fine powders to The powdered components reduced to fine powders to

prevent grittinessprevent grittiness

Fine powdered drugs are blendedFine powdered drugs are blended

Then powder are levigated with agent that is compatible Then powder are levigated with agent that is compatible

with the base, e.g., mineral oil or glycerinwith the base, e.g., mineral oil or glycerin

The amount of levigating agent equal to the material to be The amount of levigating agent equal to the material to be

levigatedlevigated

Incorporation method Incorporation method

Solid materials soluble in a solvent that is compatible Solid materials soluble in a solvent that is compatible

with the product may first be dissolvedwith the product may first be dissolved

e.g., dissolve salicylic acid crystals in alcohole.g., dissolve salicylic acid crystals in alcohol

Mix with a portion of the base until the product is smooth Mix with a portion of the base until the product is smooth

and uniformand uniform

Another portion of the base is added to the Another portion of the base is added to the

mixturemixture

The process being repeated until all of the The process being repeated until all of the

ointment base has been incorporated ointment base has been incorporated

Ointment roller mills resulting in a products Ointment roller mills resulting in a products

that are smooth and uniform in composition that are smooth and uniform in composition

and textureand texture

INCORPORATION OF LIQUIDSINCORPORATION OF LIQUIDS

For aqueous solutions:For aqueous solutions:

Water-absorbable or hydrophilic ointment bases are suitableWater-absorbable or hydrophilic ointment bases are suitable

In oleaginous ointment base, a portion of the base must In oleaginous ointment base, a portion of the base must

be replaced with a hydrophilic base, be replaced with a hydrophilic base,

Incorporates the solution in it, and mixes the product Incorporates the solution in it, and mixes the product

with the original basewith the original base

For Alcoholic solutionsFor Alcoholic solutions

Oleaginous vehicles or emulsion bases are suitableOleaginous vehicles or emulsion bases are suitable

Other liquid materials as natural balsams Other liquid materials as natural balsams (Peru balsam) (Peru balsam)

It is difficult to be incorporated into ointment bases It is difficult to be incorporated into ointment bases

Mix balsam with an equal portion of castor oil before Mix balsam with an equal portion of castor oil before

incorporating it into the baseincorporating it into the base

This procedure reduces the surface tension of the This procedure reduces the surface tension of the

balsam balsam

and aid in distribution of the balsam through the vehicleand aid in distribution of the balsam through the vehicle

Ointment bases containing components as:Ointment bases containing components as:

beeswax, paraffin, stearyl alcohol, and high molecular beeswax, paraffin, stearyl alcohol, and high molecular

weight polyethylene glycols, which do not mix well by weight polyethylene glycols, which do not mix well by

incorporation, are prepared by fusionincorporation, are prepared by fusion

Fusion methodFusion method

The components of an ointment are combined by being The components of an ointment are combined by being

melted together and cooled with constant stirring until melted together and cooled with constant stirring until

congealedcongealed

Components not melted are added to the congealing Components not melted are added to the congealing

mixture during cooling and stirringmixture during cooling and stirring

Heat-labile and volatile substances are added when the Heat-labile and volatile substances are added when the

temperature of the mixture is low enoughtemperature of the mixture is low enough

Many substances are added to the congealing Many substances are added to the congealing

mixture in solution, others are added as insoluble mixture in solution, others are added as insoluble

powders levigated with a portion of the basepowders levigated with a portion of the base

Once congealed, the ointment may be passed Once congealed, the ointment may be passed

through an ointment mill to ensure a uniform through an ointment mill to ensure a uniform

texturetexture

If the item having the highest melting point is If the item having the highest melting point is

melted first and the other components are added to melted first and the other components are added to

this hot liquid, all the components will be subjected this hot liquid, all the components will be subjected

to this high temperature, irrespective of their own to this high temperature, irrespective of their own

individual melting pointsindividual melting points

By melting the component having the lowest By melting the component having the lowest

melting point first and adding the components of melting point first and adding the components of

higher melting points in order of their individual higher melting points in order of their individual

melting points a lower temperature is usually melting points a lower temperature is usually

sufficient to achieve fusionsufficient to achieve fusion

*This is due to the solvent action exerted by the first *This is due to the solvent action exerted by the first

melted component on the other componentsmelted component on the other components

In the preparation of ointments having an In the preparation of ointments having an

emulsion type:emulsion type:

Melting process and emulsification process are usedMelting process and emulsification process are used

The water immiscible components such as oil and The water immiscible components such as oil and

waxes are melted together in a steam bath to aboutwaxes are melted together in a steam bath to about

70 to 75°C70 to 75°C

Aqueous solution of all of the heat-stable, water-soluble Aqueous solution of all of the heat-stable, water-soluble

components is prepared in the amount of water in the components is prepared in the amount of water in the

formula and heated to the same temperature as the formula and heated to the same temperature as the

oleaginous componentsoleaginous components

The aqueous solution is slowly added to the melted The aqueous solution is slowly added to the melted

oleaginous mixture, with constant stirringoleaginous mixture, with constant stirring

The temperature is maintained for 5 to 10 minutes The temperature is maintained for 5 to 10 minutes

to prevent crystallization of waxes.to prevent crystallization of waxes.

Then the mixture is slowly cooled with the stirring Then the mixture is slowly cooled with the stirring

until congealinguntil congealing

Preservation of OintmentsPreservation of Ointments

Semisolid preparations as ointments especially Semisolid preparations as ointments especially

those utilizing bases which contain water require those utilizing bases which contain water require

the addition of antimicrobial preservatives to the addition of antimicrobial preservatives to

inhibit the contaminationinhibit the contamination

Using preservatives as p hydroxybenzoates, Using preservatives as p hydroxybenzoates,

phenols, benzoic acid, sorbic acid, quaternary phenols, benzoic acid, sorbic acid, quaternary

ammonium saltsammonium salts

Ultra filtration of the vehicle and using aseptic Ultra filtration of the vehicle and using aseptic

manufacturing processesmanufacturing processes

Packaging and Storage of OintmentsPackaging and Storage of OintmentsPackaging and Storage of OintmentsPackaging and Storage of Ointments

Semisolid preparations must be protected Semisolid preparations must be protected

through proper packaging and storage from the through proper packaging and storage from the

destructive influences of air, light, moisture, and destructive influences of air, light, moisture, and

heat, and the possible chemical interactions heat, and the possible chemical interactions

between the preparation and the container between the preparation and the container

Opaque and colored-glass containers are useful for Opaque and colored-glass containers are useful for

ointments containing drugs that are light sensitiveointments containing drugs that are light sensitive

Jars for ointments may vary in size from as little as 1/2 oz Jars for ointments may vary in size from as little as 1/2 oz

to 1lb or moreto 1lb or more

Ointments are usually

packaged

either in jars or in tubes May be made of Plastic or glass, May be made of Plastic or glass,

uncolored, colored green, amber, or uncolored, colored green, amber, or

blue, or opaque and porcelain-white.blue, or opaque and porcelain-white.

Ointment jars are filled by forcing the ointment down and Ointment jars are filled by forcing the ointment down and

along the sides of the jar to avoid the entrapment of airalong the sides of the jar to avoid the entrapment of air

Ointments prepared by fusion may be poured directly into Ointments prepared by fusion may be poured directly into

the ointment jars for congealing within the jarthe ointment jars for congealing within the jar

Most ointments must be stored at temperatures below Most ointments must be stored at temperatures below

30°C to avoid the softening and liquefying of the base, 30°C to avoid the softening and liquefying of the base,

o to prevent settling of insoluble medicaments to the bottom to prevent settling of insoluble medicaments to the bottom

of the containersof the containers

o to prevent separation of emulsionto prevent separation of emulsion

bases into two phasesbases into two phases

Some tubes co-packaged with special tips when the Some tubes co-packaged with special tips when the

ointment is to be used for rectal, ophthalmic, vaginal or ointment is to be used for rectal, ophthalmic, vaginal or

nasal applicationnasal application

Tubes of ointments for topical use are of Tubes of ointments for topical use are of 5 g to 30 g size5 g to 30 g size

TubeTubess

The collapsible tubes are The collapsible tubes are

made of made of tin or plastictin or plastic

Tubes of ointments for ophthalmic use are Tubes of ointments for ophthalmic use are

most commonly packaged in small, tin or most commonly packaged in small, tin or

plastic collapsible tubes holding about 3.5 g plastic collapsible tubes holding about 3.5 g

of ointmentof ointment

Tubes are filled by pressure fillers from the open back end Tubes are filled by pressure fillers from the open back end

which is then closed and sealedwhich is then closed and sealed

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

contaminants and are more stablecontaminants and are more stable

than ointments packaged in jarsthan ointments packaged in jars

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