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琥珀酸美托洛尔和氢氯噻嗪包衣压片的制剂开发。

Formulation development of metoprolol succinate and hydrochlorothiazide compression coated tablets.

机构信息

Maliba Pharmacy College, Bardoli Mahuva Road, Tarsadi, Surat 394 350, India.

出版信息

Curr Drug Deliv. 2013 Dec;10(6):631-44. doi: 10.2174/156720181006131125145201.

Abstract

The purpose of present research work was to design and optimize compression coated tablet to provide an immediate release of hydrochlorothiazide in stomach and extended release of metoprolol succinate in intestine. Compression coated tablet was prepared by direct compression method which consisted of metoprolol succinate extended release core tablet and hydrochlorothiazide immediate release coat layer. Barrier coating of Hydroxy Propyl Methyl Cellulose (HPMC) E15LV was applied onto the core tablets to prevent burst release of metoprolol succinate in acidic medium. A 32 full factorial design was employed for optimization of the amount of polymers required to achieve extended release of drug. The percentage drug release at given time Q3, Q6, Q10, Q22; were selected as dependent variables. Core and compression coated tablets were evaluated for pharmaco-technical parameters. In vitro drug release of optimized batch was found to comply with Pharmacopoeial specifications. Desired release of metoprolol succinate was obtained by suitable combination of HPMC having high gelling capacity and polyethylene oxide having quick gelling capacity. The mechanism of release of metoprolol succinate from all batches was anomalous diffusion. Optimised batch was stable at accelerated conditions up to 3 months. Thus, compression coated tablet of metoprolol succinate and hydrochlorothiazide was successfully formulated.

摘要

本研究工作的目的是设计和优化压缩涂层片剂,以提供氢氯噻嗪在胃中的即刻释放和琥珀酸美托洛尔在肠中的延长释放。压缩涂层片剂通过直接压缩法制备,该方法由琥珀酸美托洛尔延长释放核心片剂和氢氯噻嗪即刻释放包衣层组成。将羟丙基甲基纤维素(HPMC)E15LV 的阻隔涂层施加到核心片剂上,以防止琥珀酸美托洛尔在酸性介质中爆发释放。采用 32 全因子设计优化达到药物延长释放所需的聚合物用量。在给定时间 Q3、Q6、Q10、Q22 下的药物释放百分比 Q3、Q6、Q10、Q22 被选为因变量。对核心和压缩涂层片剂进行了药代动力学参数评估。优化批的体外药物释放符合药典规范。通过具有高凝胶能力的 HPMC 和具有快速凝胶能力的聚乙烯氧化物的合适组合,获得了琥珀酸美托洛尔的所需释放。所有批次中琥珀酸美托洛尔的释放机制都是异常扩散。优化批在加速条件下稳定长达 3 个月。因此,成功地制备了琥珀酸美托洛尔和氢氯噻嗪的压缩涂层片剂。

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