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一种用于口服控释高溶解性酒石酸美托洛尔的三层瓜尔胶基质片剂。

A three-layer guar gum matrix tablet for oral controlled delivery of highly soluble metoprolol tartrate.

作者信息

Krishnaiah Y S R, Karthikeyan R S, Satyanarayana V

机构信息

Department of Pharmaceutical Sciences, College of Engineering, Andhra University, Visakhapatnam 530 003, India.

出版信息

Int J Pharm. 2002 Jul 25;241(2):353-66. doi: 10.1016/s0378-5173(02)00273-9.

Abstract

The objective of the study is to design oral controlled drug delivery systems for highly water-soluble drugs using guar gum as a carrier in the form of a three-layer matrix tablet. Metoprolol tartrate was chosen as a model drug because of its high water solubility. Matrix tablets containing either 30 (M1), 40 (M2) or 50% (M3) of guar gum were prepared by wet granulation technique using starch paste as a binder. Three-layer matrix tablets of metoprolol tartrate were prepared by compressing on both sides of guar gum matrix tablet granules of metoprolol tartrate M1, M2 or M3 with either 50 (TL1M1, TL1M2 or TL1M3) or 75 mg (TL2M1, TL2M2 or TL2M3) of guar gum granules as release retardant layers. Both the matrix and three-layer matrix tablets were evaluated for hardness, thickness, drug content uniformity, and subjected to in vitro drug release studies. The amount of metoprolol tartrate released from the matrix and three-layer matrix tablets at different time intervals was estimated by using a HPLC method. Matrix tablets of metoprolol tartrate were unable to provide the required drug release rate. However, the three-layer guar gum matrix tablets (TL2M3) provided the required release rate on par with the theoretical release rate for metoprolol tartrate formulations meant for twice daily administration. The three-layer guar gum matrix tablet (TL2M3) showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months. The FT-IR study did not show any possibility of metoprolol tartrate/guar gum interaction with the formulation excipients used in the study. The results indicated that guar gum, in the form of three-layer matrix tablets, is a potential carrier in the design of oral controlled drug delivery systems for highly water-soluble drugs such as metoprolol tartrate.

摘要

本研究的目的是使用瓜尔胶作为载体,以三层基质片剂的形式设计用于高水溶性药物的口服控释给药系统。由于酒石酸美托洛尔具有高水溶性,因此选择其作为模型药物。采用淀粉糊作为黏合剂,通过湿法制粒技术制备了分别含有30%(M1)、40%(M2)或50%(M3)瓜尔胶的基质片剂。通过在瓜尔胶基质片剂颗粒两侧压制含有50(TL1M1、TL1M2或TL1M3)或75mg(TL2M1、TL2M2或TL2M3)瓜尔胶颗粒作为缓释层的酒石酸美托洛尔颗粒,制备了酒石酸美托洛尔三层基质片剂。对基质片剂和三层基质片剂进行了硬度、厚度、药物含量均匀度评估,并进行了体外药物释放研究。采用高效液相色谱法测定不同时间间隔从基质片剂和三层基质片剂中释放的酒石酸美托洛尔的量。酒石酸美托洛尔基质片剂无法提供所需的药物释放速率。然而,三层瓜尔胶基质片剂(TL2M3)提供了与用于每日两次给药的酒石酸美托洛尔制剂的理论释放速率相当的所需释放速率。三层瓜尔胶基质片剂(TL2M3)在40℃/75%相对湿度下储存6个月后,其外观、药物含量或溶出模式均无变化。傅里叶变换红外光谱研究表明,酒石酸美托洛尔/瓜尔胶与研究中使用的制剂辅料没有相互作用的可能性。结果表明,以三层基质片剂形式存在的瓜尔胶是设计用于高水溶性药物(如酒石酸美托洛尔)的口服控释给药系统的潜在载体。

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