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Seminar principles of topical therapy


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topical therapy, factors that affect absorption, frequency of applicatoin, preparations, creams, ointments, lotions, gels

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Seminar principles of topical therapy

  1. 1. Seminar presentation Principles of Topical Therapy Moderator:- Dr. R. S. Meena
  2. 2. • The skin has a surface area of 1.6-2 m2 • This area enables the enhancement of systemic treatment measures • An extensive region for the application and absorption of topical medications • The active ingredients penetrate the skin either via transepidermal or transfollicular pathways
  3. 3. • Sensible topical drug therapy involves not only the selection of an appropriate agent, but also a thoughtful consideration of the areas of the body affected. • Basic principles1. State of the diseased skin(Pathologic changes) 2. Age of patient 3. Area of the body 4. Concentration of the drug 5. Type of vehicle (e.g., ointment, cream, lotion) 6. Method of application 7. A defined duration of use that both maximizes efficacy and minimizes adverse side effects.
  4. 4. FACTORS THAT AFFECT ABSORPTION CUTANE OUS DRUG DELIVERY Therapeutic efficacy-relates to both its inherent potency and its ability to penetrate the skin. Percutaneous absorption necessitates passage through the stratum corneum, epidermis, papillary dermis, and into the bloodstream. Topical medicines generally have a poor total absorption . But it does not necessarily translate into low efficacy. Stratum Rate-limiting barrier to percutaneous drug delivery. Composed of Corneum ceramides, free fatty acids, and cholesterol in a 1:1:1 molar ratio and By weight 50%, 35 % and 15% respectively. Drug penetration, will vary depending on body site, due to its thickness. Diseased skin- Abraded or eczematized skin presents less of a barrier. Solvents, surfactants, and alcohols can denature the cornified layer and increase penetration Occlusio n Range from application under an airtight dressing such as vinyl gloves or plastic wrap, to occlusion with cotton gloves or socks at night for treatment of hands and feet, to application of a medication already impregnated into an airtight dressing, as seen in flurandrenolide (Cordran) tape. Greatest benefit-should hydrate the skin by immersion in water. It increased- both efficacy and side effects .
  5. 5. • • • • • • • • • • • Regional Differences in Penetration in decreasing orders 1.Mucous membrane 2. Scrotum 3. Eyelids 4. Face 5.Chest and back 6.Upper arm and legs 7.Lower arm and legs 8.Dorsa of hand and feets 9.Palmer and planter skin 10.Nails
  6. 6. Frequency of Application • Must be specified in order to maximize the response whilst avoiding side effects such as irritation. • Emollients should be applied frequently enough to maintain their physical effect. • Active preparations are usually applied just once or twice a day. • As a general rule, twice daily application of drugs such as corticosteroids or deltanoids is only marginally more effective than once daily application. • Increasing the interval between applications can be a useful method of gradually reducing the intensity of a treatment, especially when it is difficult to do so by using a lower concentration or less potent agent.
  7. 7. Drug concentration • The concentration is usually written as a percentage representing the proportion of the formulation, by weight, which is the active constituent. • A concentration of 1% indicates that 1 g of drug will be contained in 100 g of the formulation. • 1% solution contains 1 g of drug in 100 ml of the formulation. • Abbreviations w/w (weight in weight) and w/v (weight in volume) are often employed to indicate which convention is being used. • Concentration of a solution is in ‘parts’; thus a 1 part in 1000 solution of potassium permanganate contains 1 g in 1 L of solution, which could be expressed as 0.1% (w/v).
  8. 8. Quantity of Application • The total quantity to be dispensed should be specified and it is helpful to inform the patient how long the prescribed quantity is expected to last. • Estimates of the quantity of cream or ointment have varied. • In one study a range of 12–27 g (average 18 g) was required for applications by ‘trained operators’, whilst a range of 8–115 g (average 44 g) was required when the treatment was self administered. • In a more 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.
  9. 9. Quantities (g) of medication required for twice daily application to the entire body at various ages. Age Requirement Daily (g) 8 Weekly (g) 3 months 8 56 6months 10 67 12 months 12 84 18 months 13 93 2 years 14 95 3 years 16 112 4 years 19 135 5 years 20 140 7 years 25 172 10 years 30 210 12 years 37 256
  10. 10. Approximate quantities (g) required for each application of Medication to different anatomical regions. Anatomical region Males Females Trunk (including buttocks) 6.6 5.8 One leg 2.9 2.5 One foot 0.9 0.7 One arm and forearm 1.7 1.3 One hand 0.6 0.5 Face, neck and ears 1.3 0.9 Whole body 20 17
  11. 11. Fingertip unit- An approximate but practical measure of topical medication is the fingertip unit. •This is the quantity of ointment, extruded from a tube with a nozzle of 5 mm diameter (note that nozzles do vary somewhat), extending from the distal crease of the forefinger to ventral aspect of the fingertip. fingertip unit •This unit weighs approximately 0.49 g in males and 0.43 g in females and covers, on average, an area of approx 300 cm2. The fingertip unit.
  12. 12. Fingertip units required for a single treatment of various regions in children and adults adapted from. The unit is measured using an adult finger. Age Face and One upper One lower Trunk neck limb limb Whole body 3–6 month 1 1 1.5 2.5 8.5 1–2 years 1.5 1.5 2 5 13.5 3–5 years 1.5 2 3 6.5 18 6–10 years 2 2.5 4.5 8.5 24.5 Adult 2.5 4.5 7.6 13.5 40
  13. 13. Compliance • Generally, adherence to a treatment regimen is associated with female gender, employment, being married, and low prescription costs. • Lower adherence is seen for patients with extensive disease, and paradoxically, Disease on the face. • Furthermore, compliance is negatively affected by depression, which is common in people with chronic skin conditions and found in up to 20 percent of patients with psoriasis.
  14. 14. Miscellaneous Factors • Vigorous rubbing or massaging of the drug -increases the surface area and blood supply to the area locally, augmenting systemic absorption . • Presence of hair follicles on a particular body site also enhances drug delivery with the Scalp and beard areas presenting less of a barrier when compared with the relatively Hairless body sites. • Skin of older individuals is poorly hydrated, with fewer hair follicles and therefore may impede drug delivery. • Reducing the particle size of the active ingredient increases its surface area-volume ratio, allowing for a greater solubility of the drug in its vehicle.
  15. 15. CLASSIFICATION AND CLINICAL APPLICATION OF TOPICAL FORMULATIONS • The vehicle is the inactive part of a topical preparation that brings a drug into contact with the skin. • Beneficial non-specific effectsCooling, protective, emollient, occlusive, or astringent properties. • Functions optimally when it is stable both chemically and physically and does not inactivate the drug. • It also should be nonirritating, nonallergenic, cosmetically acceptable, and easy to use. • Additionally, the vehicle must release the drug into the pharmacologically important compartment of the skin. • Finally, the patient must accept using the vehicle or else compliance will be poor.
  16. 16. Frequently employed constituents of vehicles Lipids Castor oil, Cetyl alcohol, Cocoa butter, Isopropyl myristate, Isopropyl palmitate, Lanolin, Liquid paraffin, Shea butter, Stearic acid, Stearyl alcohol, White soft paraffin (petrolatum) Emulsifiers Alkyl sulphates and sulphonates, Glyceryl monostearate, Lanolin and derivatives, Phosphoric acid esters, Polyethylene glycols, Polyvalent metallic soaps, Propylene glycol fatty acid esters, Quaternary ammonium cationic compounds, Sorbitan monolaurate, monopalmitate and mono-oleate, Triethanolamine oleate Humectants Gelatine, Glycerin, Propylene glycol, Pyrrolidone carboxylic acid, Sorbitol, Urea Penetration enhancers Azone, Dimethyl sulphoxide, Propylene glycol, Salicylic acid, Urea Preservative s Benzyl alcohol, Butylated hydroxyanisole, Butylated hydroxytoluene Chlorocresol, Edetic acid/disodium edetate, Hydroxybenzoates (parabens), Propylene glycol, Sodium metabisulphite, Sorbic acid/sorbates Solvents Acetone, Ethanol, Ether, Chloroform, Glycerin, Isopropyl alcohol Methanol, Propylene glycol, Water
  17. 17. Powders Absorb moisture and decrease friction Used in the intertriginous areas and on the feet Eg. antifungals Contain zinc oxide eg. calamine (antiseptic and covering properties), talc (lubricating and drying properties), and stearate (improved adherence) Poultices Wet solid mass (cataplasm of particles, ) sometimes heated, that is applied to diseased skin Used as wound cleansers and absorptive agents in exudative lesions such as decubiti and leg ulcers. Historically, contained meal, herbs, plants, and seeds. Modern poultice often consists of porous beads of dextranomer. Ointments Semisolid preparations that spread easily. Protective, hydrating, Classified into five categories: and lubricating. Hydrocarbon bases, Absorption bases, Emulsions of water-in-oil, Emulsions of oil-in-water, and Water-soluble bases. Dermatologists commonly refer to the hydrocarbon bases and absorption bases as ointments and the water-in-oil/oil-in-water emulsion bases as creams. In pharmaceutical terms, all of these preparations are ointments.
  18. 18. HYDR0CARB0N BASES (oleaginous bases) Composed of a mixture of hydrocarbons of varying molecular weights, m.c. petrolatum Greasy and can stain clothing. stable and do not contain preservatives. not used for watersoluble drugs. silicon ointments are composed of alternating oxygen and silicon atoms bonded to organic groups, such as phenyl or methyl, and are excellent skin protectants. ABSORPTI0N BASES Contain hydrophilic substances that allow for the absorption of water-soluble drugs. Lubricating and hydrophilic, can form emulsions. Function as emollients and protectants Greasy but easier to remove, do not contain water. Eg. anhydrous lanolin and hydrophilic petrolatum.
  19. 19. CREAMS( WATERIN-0IL EMULSIO N) By definition, contains <25% water, with oil being the dispersion medium. two-phase systems may separate unless shaken Less greasy, spread easily, and provide a protective film of oil, slow evaporation of the water phase provides a cooling effect Emulsifier( or surfactant) is soluble in both phases and surrounds the dispersed drops to prevent their coalescence. Preservatives are frequently added to increase the emulsion's shelf life. Eg. surfactants- sodium lauryl sulfate, the quaternary ammonium Compounds, Spans( sorbitan fatty acid esters), and Tweens (polyoxyethyiene sorbian fatty acid esters). Oil-inwater Emulsion s Contains >31 % water. Contain preservatives, such as the parabens, to inhibit the growth of molds. Spread very easily, are water washable and less greasy, and are easily removed from the skin and clothing. Contain a humectant (an agent that draws moisture into the skin), such as glycerin, propylene glycol, or polyethylene glycol(PEG), to prevent the cream from drying out. oil phase may contain either cetyl or stearyl alcohol (paraffin alcohols) to impart a stability and velvety smooth feel upon application to the skin.
  20. 20. Water- Consist either primarily Water soluble, require no soluble or completely of various PEGs. preservative bases Depending on their M.W., PEGs are either liquid (eg. PEG 400) or solid (PEG 4000). Gels additives. nonstaining, greaseless, and easiiy washed off of the skin Made from watersoluble bases by formulating water, propylene glycol, and/or PEGs with a cellulose derivative or carbopol. Newer gel contain the humectant glycerin, the emollient dimethicone, or the viscoelastic polysaccharide hyaluronic acid Clear and ease of both application and removal. Easy to use on the hair-bearing body sites It will be useful in scenarios where the practitioner desires a high surface concentration and low percutaneous absorption of the drug. e.g. topical antifungal and antibiotics (mupirocin). They lack any protective or emollient properties. If they contain high concentrations of alcohol or propylene glycol, they tend to be drying or cause stinging. Gels require preservatives. After application the aqueous or alcoholic component evaporates, and the drug is deposited in a concentrated form.
  21. 21. Pastes High concentrations of powders (up to 50 %) into an ointment such as a hydrocarbon base or a water-in-oil emulsion Must be insoluble in the ointment. Stiffer than the original ointment. Commonly used are zinc oxide, starch, calcium carbonate, and talc. Solution Dissolution of two or Liquid vehicle may be more substances into aqueous, homogenous clarity hydroalcoholic, or non-aqueous (alcohol, oils, or propylene glycol). Liniment s Non-aqueous solutions of drugs in oil or alcoholic solutions of soap. Function- localize the effect of a drug that may be staining or irritating (i.e. anthralin). Impermeable barriers that serve as protectants or sunblocks. Less greasy than ointments, more drying, and less occlusive. Aqueous solution- aluminum acetate or Burow's solution. Hydroalcoholic solution with 50% alcohol is called a tincture. Base of oil or soap Used as counterirritants, facilitates application astringents, antipruritics, to the skin with emollients, and analgesics. rubbing or massage.
  22. 22. Coliodion Non-aqueous solution Flexible collodions have added castor oil of pyroxylin in a and camphor and are used, eg. to deliver mixture with ether and 10% salicylic acid as a keratolytic agent. ethanol applied to the skin with a soft brush Suspension Two-phase system or Lotion consisting of a finely divided, insoluble drug dispersed into a liquid in a concentration of up to 20%. Eg. calamine lotion, steroid lotions, and emollients containing urea or lactic acid easier to apply and allow for uniform coating of the affected area, and are often the favorite preparation in treating children. more drying than ointments. Shake lotions Application of shake lotions effectively dries and cools wet and weeping skin. consist of zinc oxide, talc, calamine, glycerol, alcohol, and water, to which specific drugs and stabilizers may be added. Powder is added to Lotions to increase the surface area of evaporation
  23. 23. Aerosols Formulating the drug in a solution within a pure propellant. Propellant is a blend of nonpolar hydrocarbons. Used to deliver drugs formulated as solutions, suspensions, emulsions, powders, and semisolids. applied to abraded or eczematized skin, aerosols lack the irritation of other formulations. Aerosol foams Contains the drug within an emulsion formulated with a foaming agent(a surfactant), A solvent system (such as water and ethanol), and a propellant. Used to deliver corticosteroids such as betamethasone valerate and clobetasol propionate. On application, a foam lattice forms transiently until it is broken by both the heat of the skin and the heat of rubbing the foam onto the skin. Thickening Increase the viscosity of agents products or suspend ingredients in a formulation Eg. beeswax and carbomers. Addition to functioning as an ointment vehicle, petrolatum may be added to an emulsion to increase its viscosity. Ingredient ay have a therapeutic effect as well as acting as part of a vehicle.
  24. 24. Stabilizers • Non-therapeutic ingredients and include the preservatives, antioxidants, and chelating agents. • Preservatives protect the formulation from microbial growth. • The ideal preservative is effective at a low concentration against a broad spectrum of organisms, nonsensitizing, odor free, color free, stable, and inexpensive. • Unfortunately, the ideal preservative does not exist.
  25. 25. • The parabens are the most frequent added preservatives, and are active against molds, fungi, and yeasts, but less effective against bacteria. • Alternative agents include the halogenated phenols, benzoic acid, sodium benzoate, formaldehyde, the formaldehyde-releasing agents, and previously, thimerosal. • Most commonly used preservatives may act as contact sensitizers.
  26. 26. • Antioxidants or preservatives prevent the drug or vehicle from degrading via oxidation. • Examples include butylated hydroxyanisole and burylated hydroxytoluene, used in oils and fats. • Ascorbic acid, sulfites, and sulfur-containing amino acids are used in water soluble phases. • Chelating agents, such as sodium EDTA and citric acid, work synergistically with antioxidants by complexing heavy metals in aqueous phases.
  27. 27. When do we use topical treatment? • If a patient has a skin disorder covering < 30% of body, the topical medication may be considered.
  28. 28. Choice of vehicles • Three main determinants to choose the right vehicle are: Patient’s skin type Degree of acuity of the disease Nature of the lesions
  29. 29. Choice of vehicles • Skin type: About 50% of individuals have oily skin or seborrhea. • They do better with creams, lotions, or shake lotions while the ones with dry skin do better with ointments or pastes. • Degree of acuity: Acute inflammatory processes are best treted with creams or lotions. • If the lesions are weeping, shake lotions are fine.
  30. 30. Choice of vehicles for different lesions
  31. 31. Topical agents Ⅰ Classification Action Smooth agents reduce friction avoid stimulation Antimycotics Antiseptics Drug Concentration(%) calamine talc zinc oxide kill or inhibition sulphur Glacial Acetic Acid benzonic acid salicylic acid clotrimazole Miconazole Terbinafine kill or inhibition boracic acid potassium permanganate Neomycin revanol 10-15 10-70 20-50 5—10 5--30 6--12 5--10 2---3 2 1 3---4 1/2000 1/5000 0.5-1 0.1
  32. 32. Topical agents Ⅱ Classification Antipruritics Action narcotism、 dimimish inflammation stop itchness Drug Concentration(%) cool mint carbolic acid bendazolecain dexamethasone triamcinolone Keratoplastics promote normal keratosis pityrol shrink blood vessel coal tar reduce effusion and resorcinol inflammatory infiltration salicylic acid 1---5 0.2-3 1---2 3---5 0.025 0.025 3---5 5--40 2---5 3
  33. 33. Topical agents Ⅲ Classification Action Concentration(%) keratolytics Drug hyperkeratosis salicylic acid make keratinocytes loose resorcinol separate and fall off Glacial Acetic Acid urea Caustics remove granulation carbolic acid tissue and neoplasm Glacial Acetic Acid salicylic acid trichloroaceticacid sunscreen absorb or prevent Titanium dioxide ultraviolet radiation depigmenting reduce pigmentation Hydroquinone agents Azelaic Acid 6--15 6--15 10-30 20-40 pure >30 >20 >30 5 3 20
  34. 34. Topical corticosteroids Potency Ultra high Class Formulation II Clobetasol propionate Cream, 0.05% Diflorasone diacetate High I Topical corticosteroid Ointment, 0.05% Amcinonide Ointment, 0.1% Betamethasone dipropionate Ointment, 0.05% Desoximetasone Fluocinonide Cream, ointment or gel, 0.05% Halcinonide III Cream or ointment, 0.025% Cream, 0.1% Betamethasone dipropionate Cream, 0.05% Betamethasone valerate Ointment, 0.1% Diflorasone diacetate Cream, 0.05% Triamcinolone acetonide Ointment, 0.1%
  35. 35. Moderate IV Ointment, 0.2% Triamcinolone acetonide Cream, 0.1% Betamethasone dipropionate Lotion, 0.02% Betamethasone valerate Cream, 0.1% Fluocinolone acetonide Cream, 0.025% Fludroxycortide Cream, 0.05% Hydrocortisone butyrate Cream, 0.1% Hydrocortisone valerate Cream, 0.2% Betamethasone valerate Lotion, 0.05% Desonide Cream, 0.05% Fluocinolone acetonide VII Ointment, 0.05% Hydrocortisone valerate VI Ointment, 0.025% Fludroxycortide Low Cream, 0.05% Fluocinolone acetonide V Desoximetasone Solution, 0.01% Dexamethasone sodium phosphate Cream, 0.1% Hydrocortisone acetate Cream, 1% Methylprednisolone acetate Cream, 0.25%
  36. 36. Side effects of topical corticosteroids • • • • • Epidermis : Atrophy Hair follicles: Steroid acne Dermis: Atrophy, striae Pigmentation: Hypopigmentation Vessels: Erythema, telangiectases
  37. 37. Hazards associated with topical treatment • M.C. - Localized irritant or allergic reactions. • This can be minimized by applying treatment at the optimal concentration and treatment intervals and by selection of the correct vehicle. • Sensitization is more difficult to anticipate and to prevent. • Contact allergy can develop not only to the active medicament but also to constituents of the vehicle. • Almost any component may sensitize; notable examples include ethylenediamine, propylene glycol, emulsifiers, sorbic acid , cetyl and stearyl alcohols and fragrances. • Patients with chronic venous eczema or leg ulcers appear to be particularly susceptible.
  38. 38. Systemic Side Effects • Rare • Absorption varies very considerably depending on the region of skin being treated. • Occlusion greatly enhances absorption. • Systemic exposure can be greater than expected in children due to their relatively high ratio of skin surface to body mass. • In the elderly, penetration of drugs may be increased as a result of changes in the structure of the skin. • This effect is most pronounced in drugs which are most hydrophilic . • Inflammation of the skin impairs barrier function and significantly increases drug absorption. • This is especially significant in the erythrodermic patient
  39. 39. •Thanks
  40. 40. Topical agents • • • • • • • • • Keratolytic agents Cytotatic agents: Podophyllin, 5-fluorouracil Retinoids Antibiotics, antifungals, antiviral agents Corticosteroids Combination products Tacrolimus, pimecrolimus Nonsteroidal antiinflammatory agents Sunscreens
  41. 41. • Class I (weakest): Hydrocortisone, prednisolone • Class II: Methylprednisolone aceponate, triamcinolone • Class III: Betamethasone 17-valerate • Class IV (strongest): Clobetasol 17-propionate
  42. 42. Formulation Ⅰ Dosage form Powder Solution Lotion Cream component action indications drug put into zinc oxide, talc and stearate Absorb moisture acute and subacute inflammation and decrease friction but no effusion astringency, protection, cooling Used in the intertriginous areas and on the feet Eg. antifungals liquid and soluble drug cooling, clear raw surface 、 acute inflammation dissolution of two or reduce inflammation with lots of effusion more substances into eg. Aqueous solutionhomogenous clarity aluminum acetate or Burrow’s solution powder and liquid protection, cooling acute and subacute mixture- two phase reduce inflammation inflammation without system (conc. Up to 20%) astringency, more drying effusion, favourite for Eg. Calamine , steroid lotions, children emolient containing urea or lactic acid consisting of aqueous protection、lubrication subacute or chronic and oily components intenerate crust inflammation ,pruritus O/W emulsion being readiy reduce inflammation diluted with water,W/O emulsion with oil Solution
  43. 43. Formulation Ⅰ Dosage form Gel • component action indications Propanediol gelatin protection, lubrication subacute or chronic of organic polymer reduce inflammation inflammation ,pruritus drug Clear and ease of both application and removal. Easy to use on the hair-bearing body sites
  44. 44. Fomulation Ⅱ action dosage form component Paste indications cream including protection、astringency 25%-50% powder intenerate crust diminish inflammation ointment vehicle with vaseline or lanolin strong action of lubrication、penetration intenerate crust tincture resolve or steep diminish inflammation drug by alcohol antipruritic subacute inflammation, scar,erosion chronic inflammation ulcer chronic inflammation sterilization pruritus
  45. 45. Fomulation Ⅱ dosage form Plastics component action organic menstruum and aqueous solution contain macromolecule compound or film agent indications protection strong percutaneous strong percutaneous action chronic inflammation