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采用毛细管吸收法将药物包埋于其中的控释片

Matrix Tablets for Controlled Release of Drugs Incorporated Using Capillary Absorption.

机构信息

Faculty of Medicine, Institute of Biomedical Sciences, University of Maribor, Taborska ulica 8, SI-2000, Maribor, Slovenia.

Faculty of Medicine, Department of Pharmacology, University of Maribor, Taborska ulica 8, SI-2000, Maribor, Slovenia.

出版信息

AAPS PharmSciTech. 2019 Jan 25;20(2):91. doi: 10.1208/s12249-019-1303-5.

Abstract

Cost and time effectiveness make direct tableting still the favored method for tablet production. Among its most noticeable limitations in application is the non-uniformity (and/or inhomogeneities) in the contents of the resulting tablets, possibly leading to inconsistencies in required tablet properties. The efficiency of direct tableting is mostly affected by surface properties of the components to be tableted, which govern the final tablet mechanical and chemical properties and can influence the liquid capillary rise that the tablets exhibit after ingestion. By using capillary rise as a driving force, we developed a simple, yet powerful procedure for filling blank tablets with a repeatable drug amount. Blank tablets were prepared by direct compression of the excipient and filled with an organic solution of hydrochlorothiazide. Tablets were characterized regarding their structure and morphology, while their applicability was monitored using in vitro drug release studies. By utilizing the mentioned filling of blank tablets, we were able to incorporate the desired dose of the drug inside while maintaining the tablets initial mechanical properties. Moreover, most of the drug was incorporated in the tablet pores and the rest was homogeneously distributed over the tablet surface in the form of small particles, by which we also eliminated content non-uniformity (homogenous drug distribution through the tablet). To sum up, we not only developed a cheap, simple, and reproducible variation of direct tableting, but were also able to eliminate some of its biggest disadvantages (e.g., segregation of components, leading to inhomogeneities in contents, and incompatibility between different base ingredients due to their different surface properties). All mentioned make the proposed approach highly interesting for future use, especially in potential therapy individualization.

摘要

成本和时间效率使得直接压片仍然是片剂生产最受欢迎的方法。在其应用中最明显的局限性之一是片剂内容物的不均匀性(和/或非均一性),这可能导致所需片剂性质的不一致。直接压片的效率主要受待压片成分的表面性质影响,这些性质决定了最终片剂的机械和化学性质,并可能影响片剂摄入后表现出的液体毛细上升。我们利用毛细上升作为驱动力,开发了一种简单而强大的方法,可重复地将药物定量填充到空白片剂中。空白片剂通过直接压缩赋形剂制备,并填充有氢氯噻嗪的有机溶液。对片剂的结构和形态进行了特征描述,同时通过体外药物释放研究监测了其适用性。通过利用所述的空白片剂填充,我们能够在保持片剂初始机械性能的同时,将所需的药物剂量纳入其中。此外,大部分药物被纳入片剂孔隙中,其余部分以小颗粒的形式均匀分布在片剂表面上,从而消除了内容物不均匀性(药物在片剂中均匀分布)。总之,我们不仅开发了一种廉价、简单且可重复的直接压片变体,而且还能够消除其一些最大的缺点(例如,成分分离,导致内容物不均匀,以及由于不同的表面性质,不同的基础成分之间不兼容)。所有这些都使得所提出的方法在未来的应用中具有很高的兴趣,特别是在潜在的个体化治疗方面。

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