The quest for new chemical entities that are pharmacologically active, as well as clinically useful, has become increasingly difficult in recent years. As a result, attention in the present day is being diverted at utilizing the already established compounds to their fullest potential. Use of novel drug delivery systems have proved to be very successful in the treatment of various diseases with many 'problem' drugs. Beta adrenergic receptor blocking agents, in general, have short biological half lives and low systemic bioavailibilities thereby necessitating multiple daily administration. This results in inconvinience and reduced compliance with the therapy. However, treatment of disease states, like hypertension and angina, with beta-blockers is a protracted process and may be required continuously for years. Most of these problems can be overcome by using a delivery device containing a protected supply of drug, from which the drug will be released at a controlled rate for a prolonged period of time. Transdermal delivery systems, containing beta-blockers, can be effectively used in the maintenance of uniform drug levels resulting in consistent pharmacologic effects and reduced side effects. The present project proposes to study seven beta-blockers, of varying solubility, for fabrication of transdermal systems. Permeation characteristics of these beta-blockers through intact hairless mouse skin will be studied and the role of each layer of skin will be evaluated. Fabrication of transdermal devices will be attempted using three different hydrophobic polymers. In depth in vitro evaluations of drug permeation characteristics through excised skins as well as polymer membranes will be performed. These will include drug release and diffusion studies. The results of these will form the basis for device fabrication. Two different approaches, namely 'monolithic' and 'membrane controlled', will be used in designing the transdermal devices. Studies on these will be designed with release characteristics for daily and weekly administration as well as for dual drug delivery. These studies should be able to establish criteria for optimal design parameters for transdermal devices containing beta- blockers. This will lay the foundation for the long term objective of making transdermal systems for human application.
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