Smal J, Marvola M, Liljequist C, Happonen I
Department of Pharmacy, University of Helsinki, Finland.
J Vet Pharmacol Ther. 1996 Dec;19(6):482-7. doi: 10.1111/j.1365-2885.1996.tb00086.x.
Furosemide is a problematic drug in a prolonged-release product because its absorption is site specific, taking place mainly in the upper parts of the alimentary tract. The aim of the study reported here was to develop prolonged-release furosemide formulations for dogs. The type of preparation selected was a hydroxypropyl methylcellulose (HPMC) matrix tablet. Evaluation was based on dissolution studies, on in vivo disintegration studies in the canine stomach and on bioavailability studies in Beagle dogs. The variables tested were the viscosity grade of the polymer, the amount of polymer and presence or absence of an alkaline compound (potassium carbonate) in the formulation. When potassium carbonate was included, furosemide was absorbed so slowly that drug administration once daily would give plateau drug plasma concentrations, even though the elimination half-life of furosemide is only about one hour. In vitro dissolution tests gave a wrong indication of the in vivo behaviour of the products. Thus, in vivo studies are important from the very beginning in the development of new drug products for dogs.
速尿制成缓释制剂存在问题，因为其吸收具有部位特异性，主要在消化道上部发生。本文报道的这项研究的目的是为犬开发速尿缓释制剂。所选制剂类型为羟丙基甲基纤维素（HPMC）骨架片。评价基于溶出度研究、犬胃内的体内崩解研究以及比格犬的生物利用度研究。所测试的变量包括聚合物的粘度等级、聚合物的用量以及制剂中碱性化合物（碳酸钾）的有无。当加入碳酸钾时，速尿吸收非常缓慢，以至于即使速尿的消除半衰期仅约1小时，每日给药一次也会使药物血浆浓度达到平稳状态。体外溶出试验对产品的体内行为给出了错误的指示。因此，在为犬开发新药产品时，从一开始进行体内研究就很重要。
