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Transcript of Include drug delivery systems and dosage forms intended to be applied to the skin. Creams Ointments...
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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