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Systems approach to vaginal delivery of drugs I: development of in situ vaginal drug absorption procedure.
Authors:T Yotsuyanagi  A Molokhia  S Hwang  N F Ho  G L Flynn  W I Higuchi
Abstract:In the framework of the development of drug delivery systems for locally administered contraceptive drugs, a reliable method that can afford quantitative evaluation of drug absorption behavior was explored using the rabit doe. A system was constructed based upon perfusing the drug solution in the vaginal tract. For this purpose, a "rib-cage" type cell was constructed and surgically implanted in the rabbit prior to an experiment. The primary purpose of the present paper is to evaluate the method, including the surgical operation and the perfusion system. The absorption experiments were carried out using n-butanol-1minus 14C as the model solute to survey the reproducibility of the absorption behavior. Experiments were conducted with a number of rabbits on several successive days to determine the day-to-day and animal-to-animal variations. The drug disappearance in the reservoir followed first-order kinetics from which the apparent permeability coefficient was calculated. The results indicated that a set of experiments may be carried out on a single animal and that the method generally affords rather high precision.
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