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$1.3 billion in 1993. Its success is based on the many advantages offered by the new formulation. Hilleman [154] performed clinical trials on 41 patients to compare efficacy, safety, compliance, and relative cost of treatment between Procardia XL and immediate release formulations. Procardia XL had fewer side effects (32% versus 58%), higher compliance rates (93% versus 76%), and lower cost of therapy ($45.71 versus $60.60). The lower cost of therapy is extremely important since managed care providers and many hospitals have implemented restrictive formularies in which cost is a major determinant of drug selection [155,156]. Clinical studies comparing Procardia XL to beta blockers Atenolol and Propranolol, with and without diuretics, were also performed [157,158]. It was concluded that Procardia XL was an effective, well-tolerated, once-a-day drug that provided a more favorable quality of life profile than did the beta blockers. |
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Worldwide drug delivery system sales were $2.5 billion in 1991 and are growing at a rate of 35% per year [159]. In addition to the major pharmaceutical companies there are at least 29 companies in the United States spending over $200 million annually in research developing new products using transdermal, iontophoretic, nasal, blood-brain, liposome, polymeric, and monoclonal antibody technologies [160]. The growth mentioned above will be achieved through technological breakthroughs in several drug delivery areas. |
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1. Abrogation of Inflammatory Responses in Transdermal Delivery |
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The world market for drugs administered transdermally is predicted to grow from $1.6 billion in 1993 to $9.1 billion in 2003 [161]. The growth rate of 20% is faster than for most other routes of administration. |
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As mentioned above, several transdermal products have been outstanding technological and marketing successes. However, most drugs cannot be delivered transdermally because they do not permeate through the skin in amounts sufficient to administer a therapeutic dose or because they irritate or sensitize the skin. Furthermore, when chemical or physical enhancers are used to increase permeation, in most cases they also increase skin irritation and sensitization. It has been postulated that more than 80% of drugs will cause skin irritation or sensitization when administered transdermally [162]. |
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Obermeyer et al. circumvented the irritation caused by chlorpheniramine delivered from cellulose triacetate membranes to humans [163]. The irritation, as well as the percutaneous absorption, were substantially reduced by reacting chlorpheniramine with undecylenic acid to form a fatty acid salt. The absorption of the salt was enhanced by dissolving it in a nonpolar nonvolatile solvent such as isopropyl oleate. |
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