Rekhi G S, Jambhekar S S
University of Maryland at Baltimore, Department of Pharmaceutical Sciences, School of Pharmacy, Baltimore 21201-1180, USA.
J Pharm Pharmacol. 1996 Dec;48(12):1276-84. doi: 10.1111/j.2042-7158.1996.tb03936.x.
The influence of formulation and extrinsic factors has been investigated for the in-vitro release of propranolol hydrochloride from controlled-release beads prepared using aqueous polymeric dispersions, Aquacoat and Surelease. A single-dose three-way crossover bioavailability study of two extended-release experimental formulations (80 mg), Inderal LA (80 mg) and an Inderal immediate-release dosage form (2 x 40 mg) was also conducted and a comparative analysis of pharmacokinetic parameters and the in-vitro release profiles was performed to assess in-vitro/in-vivo correlation. Analysis showed that the in-vitro release data appeared to follow zero-order release kinetics. Intensity of agitation and dissolution method were found to have no significant effect on drug release from beads prepared using either of the coating dispersions studied or Inderal LA. Release of drug from beads coated with Aquacoat was faster in basic media than in acidic media; Surelease-coated beads, however, showed release characteristics that were less sensitive to changes in the pH of the dissolution fluid, and Inderal LA beads showed slower release profiles in acidic medium than in other dissolution media studied. Pharmacokinetic analysis of the data revealed sustained-release absorption characteristics without any evidence of dose-dumping from any of the extended-release dosage forms studied. Regression analysis of the fraction of drug absorbed against the percentage of the drug released in-vitro, at the corresponding times, yielded good in-vitro/in-vivo correlation (level A) for all the extended-release formulations studied. The results showed that there was no dose-dumping from any of extended-release formulations and that the relative bioavailabilities of the experimental formulations were superior to that of the marketed formulation.
已经研究了制剂和外在因素对使用水性聚合物分散体Aquacoat和Surelease制备的盐酸普萘洛尔控释微丸体外释放的影响。还进行了两种缓释实验制剂（80mg）、Inderal LA（80mg）和一种Inderal速释剂型（2×40mg）的单剂量三交叉生物利用度研究，并对药代动力学参数和体外释放曲线进行了比较分析，以评估体外/体内相关性。分析表明，体外释放数据似乎符合零级释放动力学。搅拌强度和溶出方法对使用所研究的任何一种包衣分散体或Inderal LA制备的微丸中的药物释放均无显著影响。用Aquacoat包衣的微丸在碱性介质中的药物释放比在酸性介质中快；然而，用Surelease包衣的微丸显示出对溶出液pH值变化不太敏感的释放特性，并且Inderal LA微丸在酸性介质中的释放曲线比在其他所研究的溶出介质中慢。对数据的药代动力学分析揭示了缓释吸收特性，在所研究的任何一种缓释剂型中均无剂量倾泻的证据。对相应时间点药物吸收分数与体外药物释放百分比进行回归分析，对所有所研究的缓释制剂均产生了良好的体外/体内相关性（A级）。结果表明，任何一种缓释制剂均无剂量倾泻，并且实验制剂的相对生物利用度优于市售制剂。
