principles of topical therapy in dermatology
DESCRIPTION
dermatologyTRANSCRIPT
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mikhin
PRINCIPLES OF TOPICAL THERAPY
MIKHIN GEORGE THOMAS
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• Topical therapy is the use of medicaments directly on
surface of skin or mucosa
• Stratum Corneum the rate limiting barrier to percutaneous
drug delivery.
• Drug penetration is inversely proportional to the thickness
of the str corneum .
• Maximal over mucous membranes>eye lids>scrotum.
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• Surface area : 1.6-2 m sq.
• Enables the enhancement of
systemic treatment measures
• An extensive region for the
application and absorption of topical
medications
• Penetration via transepidermal or
transfollicular pathways
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PERCUTANEOUS ABSORPTION
• TRANSCELLULAR PENETRATION (across the cells)
• INTERCELLULAR PENETRATION (between the cells)
• TRANSAPPENDAGEAL PENETRATION (via hair follicles, sweat and sebaceous glands, and pilosebaceous apparatus)
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• Selection of an appropriate agent
• Thoughtful consideration of the areas of the body
affected
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1. State of the diseased skin(pathologic changes)
2. Age of the patient
3. Area of the body
4. Concentration of the drug
5. Type of vehicle
6. Method of application
7. A defined duration of use that maximizes efficacy and
minimizes adverse side effects.
BASIC
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• Drug concentration
• Thickness
• Surface area applied
• Friction and heat
• Occlusion
- Cover skin surface easily, mix readily with sebum
- Promotes hydration of skin
- Hair follicles
FACTORS AFFECTING PERCUTANEOUS ABSORPTION
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• Vinyl gloves or plastic wrap, occlusion with cotton gloves or socks .
•Greatest benefit – increased hydration
•Increases efficacy as well as side effects .
OCCLUSION
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• Specify concentration of the drug, the vehicle and the frequency of application.
• Quantity to be used.
• Precisely where it should be/should not be applied.
• Timing of application in relation to bathing or other treatments.
• Warn regarding potent irritant or allergic effects, factors that influence systemic absorption.
PRESCRIBING TOPICAL TREATMENT
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• w/w : % representing proportion of the formulation, by weight, which is the active constituent. ( 1% = 1 g of drug in 100g formulation)
• w/v : % representing proportion of the volume of the formulation.( 1% = 1 g in 100ml)
• ‘parts’ : describe conc. of solution (1 part in 1000 solution contains 1 g in 1L = 0.1 % w/v)
DRUG CONCENTRATION
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FREQUENCY OF APPLICATION
• Maximize response whilst avoid side effects.
• Excessive application – systemic exposure
• Emollients- Frequent application several times a day
• Active preparations – once or twice a day.
• Pharmacological actions persist long after drug has left the skin surface.
• Increasing interval bet. applications effective way of tapering intensity of treatment.
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QUANTITY TO BE APPLIED
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• Fingertip unit:
- Qty of ointment, extruded from a tube with nozzle 5 mm diameter, extending from distal crease of forefinger to ventral aspect of fingertip.
- O.49 g in males, 0.43 g in females; covers area appx 300 cm sq.
• Rule of hand:
- Area of the size that can be covered by four adult hands can be treated by 1g of ointment or two FTUs.
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FTU per body site:
AGE Face & Neck
One upper limb
One lower limb
Trunk Whole body
ADULT 2.5 4.5 7.6 13.5 40
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• Estimates of the quantity of cream or ointment have
varied.
• Recent study : male patients treating themselves,
applied an average of 20 g of ointment, and females
applied 17 g.
• Quantity required for 1 week of once-daily
application to the whole body would be
approximately 140 g for males and 120 g for
females.
QUANTITY OF APPLICATION
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SITE Relative levels of
absorption%
Forearm 1.0
Sole 0.1
Palm 0.8
Back 1.7
Scalp 3.5
Axilla 3.6
Forehead 6.0
Scrotum 42
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CLEANSING MEASURES
1. Soap and water wash
2. 3% solution hydrogen peroxide or saline
wash
3. Wet dressings
4. Soaking with grease or oils
5. After using the above said cleansing measures
, mechanical removal of crusts and scales
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VEHICLE
•Substances that bring specific drugs
into contact with the skin
•Non specific effect- cooling,
protective, emollient, occlusive,
astringent, carrier.
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CHOICE OF VEHICLE
1. Reservoir : local release
2. Delivering the active drug
3. Beneficial effects like astringent, cooling, soothing, lubricating, occlusive, protective.
Types of vehicles:
4. Monophasic: liquids, powders, grease
5. Biphasic: Lotion, paste, cream, ointment
6. Triphasic: cooling paste
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CHOİCE OF VEHİCLES
Two main determinants to choose the right vehicle are:
Patient’s skin type
Nature of the lesions
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Powders
Greasy pastes
Cooling pastes
Shake lotionsDrying pastes
Greases
w/o creams
o/w creams
Liquids
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POWDERS
• Mixture of finely divided drugs and/or chemicals in dry form.
Cooling effect
prevents friction
absorbs moisture
covering property.
• Most useful in intertriginous areas.
• Not used in oozing dermatoses due to crust formation.
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• Organic powders –
• starch
more absorbent
Prone to microbial decomposition
• Inorganic powders
- Zn oxide
- TiO2
- Stick- Lanolin
- Slip- starch, zinc stearate
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• Zinc oxide, Talcum- clean, white, absorbent
• Kaolin, Diatomaceous earth- highly absorbent
• Titanium oxide- light and puffy
• Boric acid- disinfectant properties
• Tannic acid- astringent
• Nystatin- anti candidal
• Neomycin- antibacterial
• Aluminium acetate- antiperspirants
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• Finely mulled and of small particle size
• Insoluble powder should not be dusted into open
wounds
• Previous application should be washed off
CHECKPOINT
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LIQUIDS
• Solutions = Liquid preparations that contain one or more soluble chemical substances usually dissolved in water and that do not, by reasons of their ingredient, method of preparation or use, fall into another group of products.
• Solvent for the active drug
• Cooling effect, soothing and antipruritic.
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• Water : important in Dermato therapeutics, used in creams, shake lotions, cooling pastes and wet dressings.
• Alcohol (spirit) : 94.9 to 96 % C2H5OH by volume, absolute alcohol = 99% C2H5OH
- Most useful solvent in pharmacy next to water.
• Glycerol : Trihydroxy alcohol obtained by hydrolysis of fats; clear syrupy liquid used in shake lotions
• Propylene glycol : viscous liquid miscible with water and alcohol.
• Ether : Readily evaporating liquid used in tinctures, collodions.
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PAINTS
• Aqueous, alcoholic or hydro alcoholic preparations applied to skin or mucous membrane.
Tinctures
• Solutions of active ingredients in alcohol, ether, chloroform or other organic solvents.
Advantages:
- Treatment confined to circumscribed areas.
- Water insoluble medicament as substitute for ointments.
- Ease of application and relative lack of messiness.
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PAINTS…
• Ant i ba c t e r i a l• Ant i m on i l i a l• Der m a t ophy t os i s
Gentian violet
• Antibacterial(folliculitis)Brilliant green
• In ter t r igo• Paronychia• Tinea infect ions
Castellani paint
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LOTIONS & SHAKE LOTIONS
• Lotions are liquid formulations which are usually simple suspensions or solutions of medications in water, alcohol or other liquids.
• Shake lotions are composed of an equal proportion of powders and liquids, when correctly compounded a highly viscous liquid results. Shaken well before use.
Uses
- Subacute or chronic less inflammed dermatoses.(transitional stages)
- Generalized dermatoses
- Drying action
• Avoid:
- Exudative lesions
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• Advantages:
- Convenience of application and removal
- Less chances of systemic and toxic effects
- Variations possible by altering the nature
and ratios of inert and active ingredients.
• Disadvantages
- Too drying or irritating.
- Difficulty in removing the sometimes very adherent remains of lotions, scales and secretions.
- Sting
- Sedimentation of solids in the preparation.
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BATHS
• Mode of treatment where whole or a part of the body is immersed.
• Widespread less exudative lesions.
- General cleansing baths
- Medicated baths
- Cleansing of particular body areas.
• Amount of water:
- Full length bath tub: 150 – 250 L (adults)
- For hand and foot: 5 – 10 L
• Duration: Should be limited to 30 min.
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BATHS
• Mode of treatment where whole or a part of the body is immersed.
• Widespread less exudative lesions.
- General cleansing baths
- Medicated baths
- Cleansing of particular body areas.
• Amount of water:
- Full length bath tub: 150 – 250 L (adults)
- For hand and foot: 5 – 10 L
• Duration: Should be limited to 30 min.
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• Cleansing baths:
- Removes accumulated dirt, debris, crusts, scales and adherent remains of medication.
- Temp. – 95-100 deg. F
- Washing with soft cloth and copious lather of plain white soap with < 0.0125 % of free alkali.
- Careful and repeated rinsing, warm spray followed by cool one.
- Drying immediately.
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• Medicated baths
- Removes dirt, debris, crusts
& scales, and have soothing,
antipruritic, decongestive &
anti inflammatory actions.
- Effects of active medical ingredients – antiparasitic, antieczematous, antiseborrhoiec …
- KMnO4 baths - exudative, vesicular & bullous eruptions, superficial infected dermatoses.
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- Psoralen bath- 3.75 mg/L
- Starch bath – soothing action in generalized itching
dermatoses.
- Tar bath – Psoriasis(good ventilation)
• Bran, cornstarch, Oatmeal- soothing action
• Chamomile tea in sitz bath- pruritus and eczema
• Tannic acid bath- astringent
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WET DRESSINGS
Useful form of topical therapy that consists of application of aqueous liquid preparation to the skin
Methods
• Compresses
• Soaks
-.
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Mechanical cleansing action.
Antipruritic action
Soothening agents- relieves superficial inflammation
Opens blisters, brings medications to the eroded or
ulcerating areas
Decongestant action by causing vasoconstriction.
Keratolytic action by macerating the skin.
Facilitates drainage.
Act as vehicles for drugs.
Prevents rapid change of temperature.
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• Solutions for wet dressings
Sterile water
Tap water
Any doubt- boil the water first.
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• Solutions of choice:
1. Normal saline (0.9%) – 1 tsp salt per pint (500ml) water
2. Astringents
- Burrow’s solution: 5% aluminium acetate diluted 1:20-1:40 in water.
- Condy’s compresses: Freshly prepared 1:8000 solution of KMnO4.
3. Antimicrobial agents: Silver nitrate 0.1%-0.5%, acetic acid 1%
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• Open wet dressings:
- Clean laundered unstarched cloth preferred, dipped in prepared solution, wrung and applied over the area; removed every 5-10 min and reapplied.
- 10 - 30 min.
- 3-4 times a day.
• Wring out to be soppy and not drippy
• Avoid maceration of surrounding skin
- Indicated in acute, swollen, inflamed, vesiculating or oozing dermatoses.
- Not more than 1/3rd body surface.
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• Closed wet dressings
- Protected from evaporation.
- More maceration, less cooling.
- Treatment of cellulitis, abscess.
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COMPRESSES
A/c exudative conditions
Dil KMNO4 compress
Fresh milk
Liquor alumni subacetatis(1:15-30)
Liquor alumini acetatis (Burrow’s soln)
AgNO3 soln 0.1-0.5%
Thiersch soln
EUSOL
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SOAKS
• P re f e r re d f o r e x t re m i t i e s
• C o n v e n i e n t f o r t h e p a t i e n t
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POULTICES
• H o t w e t d r e s s i n g ,
• M a i n t a i n m o i s t h e a t .
• B o i l s a n d a b s c e s s e s . C l e a n s e r s a n d a b s o r p t i v e a g e n t s i n c / c e x u d a t i v e l e s i o n s . ( s c a l p )
• P r e p a r e d f r o m p l a n t s , h e r b s a n d s e e d s ( e g : fl a x s e e d , s t a r c h ) i n t h e p a s t . N o w , p o r o u s b e a d s o f d e x t r a n o m e r
• G l y c e r i n – p r e v e n t s d r y i n g f a s t
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• Boric acid- starch poultice
1 tbsp. starch+1 tbsp. boric acid+ 2 tbsp. cold
water+ ½ cup boiling water
Corn starch preferred
Mechanism of action :
Starch+ crust glycogen
• Complication
o bleeding
o Scalding
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CREAMS
• Semisolid emulsions containing both lipid and water.
• Emulsions are suspensions, either lipid droplets in water (oil in water = o/w) or aqueous solutions suspended in an oily medium (water in oil = w/o).
• Transition between lotions and ointments.
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EMULSIFYING AGENTS
• Emulsions contain droplets of one substance, called inner or disperse phase, suspended in liquid or semisolid outer or continuous phase.
• Emulsifying agents act as interphase stabilizing emulsions.
• Eg: Emulsifying wax, cetearyl alcohol
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Emulsifier
Anionic Cationic Non ionic
•Alkyl sulphates•Soaps•Dodecyl benzene•Sulfonates•Lactylates •Sulfosuccinates •Monoglycerides •Sulfonates•Phosphate esters •Silicones •Taurates
•Quaternary ammonium compounds•alkoxyalkylamines
•Polyoxyethylene •Alkyl-aryl ethers •Polyoxy ethylene •Sorbitan esters •Sorbitan fatty acid esters •Glyceryl fatty acid esters
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W/O
Immiscible with water, difficult to
wash off
Emollient, lubricant and mildly occlusive.
{COLD CREAMS}
O/W
Water miscible
Cooling and soothing, well absorbed into
skin. {VANISHING CREAM}
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LINIMENTS
• Alcoholic or oleaginous emulsions intended for external appln. with rubbing.
• Alcoholic or hydroalcoholic vehicle- rubefacient, counterirritant, penetrant.
• Oleaginous vehicle (oils)- massage
• Shaken well before use to ensure uniform distribution of dispersed phase.
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OINTMENTS
• Semisolid preparations intended for external application.
• Ointment Bases
One of the most important ingredients used in
the formulation of topical preparations
carrier of the medicaments.
control the extent of absorption of medicaments
incorporated with them.
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Compatible with skin pH and drug
Inert ,non irritating and non sensitizing
Good solvent and/or emulsifying agent
Emollient , protective , non greasy and easily
removable
Release medicaments easily at the site of
administration
Pharmaceutically elegant and possess good
stability.
Ideal properties of a base
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BASES
OLEAGENOUS BASE
ABSORPTION BASE
EMULSION BASE
WATER SOLUBLE
BASE
Classification Of Bases
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Oleagenous ( hydrocarbon) bases:
Consist of a combination of more than one oleaginous material such as
water insoluble hydrophobic oils and fats
Highly compatible ; occlusive ; good emollients
Anhydrous, do not absorb water, hydrophobic, non washable
liquid paraffin
Uses : protective, emollient and vehicle for solid drugs.
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Absorption (Emulsifiable) base:
Have capacity to absorb considerable quantities of water or
aqueous solution
Anhydrous, water insoluble and water unwashable.
Good emollient but poor occlusive property.
Uses: protective, emollient and vehicle for aqueous solutions and
solid drug.
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Water soluble Bases:
Include both hydrous and non hydrous dermatological non - emulsion
bases which are water soluble and contain no oil phase.
Water soluble, water washable, non greasable
Because they soften with the addition of water, large amount of
aqueous solutions are not effectively incorporated into the bases.
Eg : carbowax compounds such as the polyethylene glycol bases
containing pectin, cellulose, bentonite and gelatin.
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Ointments…
Advantages:- Best occlusive
- Good hydration
- Used in chronic, dry, brittle,
lichenified dermatoses.
- Most potent effect of the drug.
- Fewer preservatives as they contain
less water and do not sustain
microorganisms.
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Ointments…
• Disadvantages:
- Difficult to spread and wash.
- Adherent to skin
- Decreased evaporation/heat loss.
- Cannot be used in acute weeping lesions and intertriginous areas.
- Cosmetically unacceptable
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DRYING PASTES & VARNISHES
Drying pastes:
• By carefully choosing the proportion between the powders and liquids; increasing the percentage of powders; possible to obtain paste like substance drying on the skin.
• Soothe and dry the skin; used along with dressings as paste bandages.
Varnishes:
• Applications which dry on the skin as a smooth, resistant, covering layer readily soluble in water.
• Prepared by dissolving powder, or a powder mixture which absorbs water and swells, in water and glycerol
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PASTES
• Semisolid preparations consisting of greases which carry in suspension insoluble, finely dispersed powders
• Equal parts of suspended powder and greasy or oily vehicle.
• Uses:
- Acute inflammation (prefer wet dressings, lotions)
- sub acute inflammation.(prefer lotions)
- Dry scaly, thickened skin conditions.(prefer ointments)
• Zinc oxide
• Talcum
• petrolatum
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• Advantages:
Comparison with ointment:
1. Thicker, drier and more solid.
2. Less impermeable, less penetrating, less macerating, less heating.
3. Stiffness permits accurate localization.
• Disadvantages:
- Greasy pastes messy and water insoluble; difficult to remove and apply.
Eg: Lassars paste – Zinc oxide 24% + Starch 24% + Salicylic acid 2% + petrolatum
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FIXED DRESSINGS
• Bandages impregnated
• Hardens and stiffens
• Flexible cast
• Unnas boot
• Excludes effects of external irritants, trauma,
scratching
• Varicose complexes of legs
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PLASTERS
• Adhere to the skin
• Macerating action
• Plantar warts, callus
• 1-7 days
• Salicylic acid, phenol
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DIRECT APPLICATION
1. Podophyllin (15-20%)
2. Silver nitrate(50%)
3. Trichloro acetic acid
4. Phenol
5. NaOH/KOH –(30-50%)
6. Resorcin – (10-50%)
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• Readily spreading
• During or after bath
• Asteatotic eczema, icthyosis, atopic dermatitis
• Coconut oil, glycerin, liq paraffin
BATH OILS
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VEHICLESPowder
s
Greasy pastes
Cooling pastes
Shake lotionsDrying pastes
Greases
w/o creams
o/w creams
Liquids
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GREASES
• True fats : Triglycerides, and waxes which are aliphatic or cyclic alcohols with one or two OH groups esterified with fatty acids
• Mineral greases : Saturated hydrocarbons of the paraffin series, petroleum distillation products.
• Advantages:
- Diluents and solvents
- EMOLLIENTS ; coats SC preventing evaporation of water, exerting softening and moisturizing effects.
- Greater absorption of drug due to occlusive effect
- Not prefered in oozy dermatoses and hairy areas.
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TRUE FATS
• Vegetable oils : composed of triglycerides which contain large proportion of unsaturated fatty acids.
- Vulnerable to oxidation- rancidity manifesting as unpleasant odour
- Eg: Olive oil, coconut oil, cocoa butter, shea butter, Castor oil, Arachis oil
• Waxes
- Beeswax- chemically stable, free cerotic acid and myricyl palmitate; thickening agent for creams, ointments.
- Emulsifying wax – cetostearyl alcohol, sodium lauryl sulphate and water
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PARAFFINS (MINERAL GREASES)
• Aromatic and unsaturated compounds eliminated; fully saturated and thus more stable and not vulnerable to oxidn.
• Examples:
- Liquid paraffin: White mineral oil, is a colourless, transparent oil of rather high viscosity.
- Petrolatum (Vaseline) : Yellow soft paraffin & White soft paraffin.
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GELS
• Might be regarded as thickened lotions.
• Semisolid preparations containing high molecular weight polymers, such as methylcellulose.
• Tendency to dry when left on the skin
• Uses:
- Treatment of scalp and other hairy areas.
- Cosmetically acceptable formulation for use on the face.
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Collodions
• Liquid preparations consisting of cellulose nitrate in organic solvent.
• Evaporate readily to leave flexible film which can hold medicaments in contact with skin.
• Uses:
- Seal minor cuts and abrasions.
- Apply salicylic acid to warts.
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MICROSPONGES
- Patented polymeric delivery systems.
- Controlled release of topical agents using microspheres, macroporous beads. (10-25 mm in diameter)
- Extremely small, inert, indestructible spheres, gets collected in the crevices of the skin and slowly release medications, time bound or in response to stimuli.(eg: rubbing, temp, pH)
- Significantly reduce irritation of effective drugs.
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LIPOSOMES
- Lipid bilayer surrounding an aqueous phase.
- Both hydrophilic and hydrophobic molecules (dissolved in membrane) delivered.
- Drug delivery by fusion of lipid bilayer with cell membrane bilayer, by diffusion or by endocytosis.
- Mainly used in cosmetics and reduce irritation from topicals.
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AEROSOLS
- Facilitates delivery of drugs formulated as solutions, suspensions, powders and semisolids.
- Drug kept in an emulsion with a foaming agent (surfactant), solvent (water or ethanol), and a propellant.
- Foam broken by heat and rubbing, dispensing thin layer of drug.
- Non irritant.
- Expensive; non eco-friendly (CFCs)
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PRESERVATIVES…
• Ointments and w/o emulsions don’t require preservatives.
• Lotions, o/w creams and gels, as they contain water, easily contaminated by bacteria.
• Animal and vegetable oils susceptible to oxidation.
• The ideal preservative is effective at a low concentration against a
broad spectrum of organisms, nonsensitizing, odor free, color free,
stable, and inexpensive
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Commonly used preservative include:
Methyl hydroxy benzoate
Propyl hydroxy benzoate
Chlorocresol
Benzoic acid
Phenyl mercuric nitrate
PRESERVATIVES
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CHOICE OF PREPARATIONS
Depends on product ; disease ; patient; condition of the skin
Condition of skin Preparation of choice
Acute inflamed, red, swollen, vesiculating or oozing dermatoses
Wet dressings, Lotions
Subacute, chronic, less inflamed Lotions, pastes, creams
Dry, scaly, thickened, lichenified Ointments, pastes
Generalized widespread eruptions
Lotions, creams
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UNSUITABLE COMBINATION OF DRUG AND VEHICLE
• Pharmaceutical incompatibility which inactivates the drug.
Zinc oxide in pastes inactivate dithranol and salicylic acid
• Ointment bases may be innapropriate for the skin condition
that is being treated
• Vehicle may bind too firmly to the drug to permit adequate
delivery into the diseased layer of skin
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CHOICE OF THE TYPE OF APPLICATION
• Irritable dermatoses- treatment to be started with bland
application such as wet dressing or cooling pastes
• Powders- for cosmetic and hygienic purposes
• Liquids – for open wet dressing in acute oozing
dermatoses.
• Occlusive wet dressings enhance drug penetration and
advantageous in hyperkeratotic and fissured conditions.
• Hydrogels- useful in dry conditions such as chapped skin
• Ointments- emollient effect, occlusive effect(disadvantage
in oozing conditions)
•
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• Environmental factors: Heat, humidity, wind, exposure to sunlight.
• Site of involvement and accessibility.
• Time of application
• Habits, occupation of the patient.
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• Hairy scalp- Shake lotion, non water washable ointment
or paste
• Ext. ear canal- shake lotion, paste
• Face- strong keratolytics, alcohol, menthol , phenol,
anthralin
• Axilla – macerating greases
• Pubic area – shake lotion
• Intertriginous – ointment or paste
CHECKPOINT (AVOID)
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HAZARDS DUE TO TOPICAL TREATMENT
• M.C. - localized irritant or allergic reactions.
Minimized by optimizing the concentration and treatment
intervals and by selection of the correct vehicle.
• Contact allergy: active medicament & constituents of the
vehicle.
o Ethylenediamine, propylene glycol, emulsifiers, sorbic acid ,
cetyl and stearyl alcohols and fragrances.
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• Rare
• Absorption depends on the region of skin being treated.
• Occlusion enhances absorption.
• Greater in children due to their relatively high ratio of skin
surface to body mass.
• Increased penetration in the elderly ; hydrophilic drugs
• Inflammation impairs barrier function and increases
absorption.
SYSTEMIC SIDE EFFECTS
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