Department of Clinical Laboratory, Huangshi Love & Health Hospital of Hubei Province, Huangshi, Hubei, China.
Department of Pharmacy, General Hospital of Central Theater of the PLA, Wuhan, Hubei, China.
PLoS One. 2022 Feb 25;17(2):e0264457. doi: 10.1371/journal.pone.0264457. eCollection 2022.
Topiramate (TPM) was an antiepileptic agent commonly used in clinical. Studies showed that an oral preparation of TPM with extended-release manner could bring some benefits for epileptics. In this paper, controlled release push-pull osmotic pump (PPOP) tablets of sparingly water-soluble TPM were successfully prepared. This bi-layer tablet core mainly consisted of sodium chloride as osmotic promoting agent and polyethylene oxide as suspending and pushing agents. The influences of osmotic agents, pushing agents and the compositions of coating membrane on TPM release profiles were evaluated. An optimal formulation of TPM-PPOP was obtained through single-factor experiments. In vitro release tests showed that the optimum formulation could release TPM at an approximate zero-order rate up to 8 h. Pharmacokinetic behaviors of TPM-PPOP tablets were evaluated and compared with the immediate release capsules after an oral single dose in beagle dogs. Pharmacokinetics results demonstrated that the TPM-PPOP tablet was able to provide a prolonged release of TPM with longer tmax and mean residence time. Lower fluctuations of drug plasma levels could also be achieved with TPM-PPOP tablets. These results suggested that sparely water-soluble drugs as TPM can be designed to PPOP for efficacy and safety use.
托吡酯（TPM）是一种常用于临床的抗癫痫药物。研究表明，具有延长释放方式的 TPM 口服制剂可为癫痫患者带来一些益处。本文成功制备了难溶性 TPM 的控释推拉式渗透泵（PPOP）片剂。该双层片剂的核心主要由氯化钠作为渗透促进剂和聚氧化乙烯作为悬浮和推动剂组成。评价了渗透剂、推动剂和包衣膜组成对 TPM 释放曲线的影响。通过单因素实验得到了 TPM-PPOP 的最佳配方。体外释放试验表明，最佳配方可在 8 小时内以近似零级速率释放 TPM。在比格犬中单剂量口服后，评价并比较了 TPM-PPOP 片剂的药代动力学行为与普通速释胶囊。药代动力学结果表明，TPM-PPOP 片剂能够提供 TPM 的延长释放，具有更长的 tmax 和平均停留时间。TPM-PPOP 片剂还可以降低药物血浆水平的波动。这些结果表明，可以设计难溶性药物如 TPM 用于 PPOP 以实现疗效和安全性。
