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Patel and Ebert found that glycerine reduces the primary irritation of moderately irritating drugs and enhancer compositions consisting of solvents and envelope-disordering compounds [164]. Govil and Kohlman patented a nicotine patch containing an antipruritic to counteract pruritus observed with the transdermal administration of nicotine [165]. Antipruritics disclosed include bisabolol, oil of chamomile, chamazulene, allantoin, D-panthenol, glycyrrhetenic acid, corticosteroids, and antihistamines. |
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Corticosteroids have also been shown to suppress cutaneous delayed hypersensitivity [166,167]. Hydrocortisone and triamcinolone acetonide 21-oic acid methyl ester have been shown to counteract the sensitization potential of a variety of sensitizers, such as clonidine, scopolamine, tetracaine, chlorpheniramine maleate, naloxone, naltrexone, nalbuphine, levorphanol, hydromorphone, buprenorphine, and 1-chloro-2,4-dinitrobenzene. |
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Cormier was granted a patent for the elimination of irritation or sensitization caused by a drug that is metabolized by an enzyme in the skin to form an irritating or sensitizing metabolite [168]. The method involves the co-administration of a metabolic modulator capable of inhibiting the enzyme from metabolizing the drug, such metabolic modulators being selected from a group consisting of tranylcypromine and phenyl alcohols. Propranolol and tetracaine are shown to be drugs that should be co-administered with metabolic modulators. |
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Franz [169] was granted US Patent 5028431 for the suppression of irritant as well as allergic contact dermatitis by using agents that compete with the arachidonic acid biotransformation such as steroids, radical scavengers, vitamin E, and leukotriene receptor antagonists. Recently a series of patents [170172] were issued for the prevention of both irritant and allergic contact dermatitis of drugs by coadministering an antigen processing inhibiting agent to inhibit the antigen processing of the drug in the lysosome. Ionophore and amphiphilic amines are disclosed as antigen-processing inhibiting agents including ammonium chloride, diethanolamine, and monensin. Treatment of sensitization has been significantly reduced by the topical administration of calcium flux inhibitors such as lanthanides and magnesium [173,174]. |
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As indicated above, a lot of progress has been achieved during the last few years in this most important area of transdermal drug delivery, with much remaining to be accomplished. These accomplishments will come through systematic research and study of the inflammatory processes and agents responsible for the initiation of the arachidonic cascade as well as through the understanding of the cellular network and signaling cascade as it pertains to the development of irritation and sensitization. |
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2. The Promise of Targeted Therapy |
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The element of targeting or site-specific delivery is in the research stage. Carriers such as liposomes, colloidal particles, albumin, nanoparticles, or water- |
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