基于聚合物无定形固体分散体技术的难溶性药物口服固体制剂开发

李思佳, 王森怡, 李凌晖, 涂迎盈, 蒋曙光

中国药学杂志 ›› 2020, Vol. 55 ›› Issue (3) : 169-176.

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中国药学杂志
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中国药学杂志 ›› 2020, Vol. 55 ›› Issue (3) : 169-176. DOI: 10.11669/cpj.2020.03.001
综述

基于聚合物无定形固体分散体技术的难溶性药物口服固体制剂开发

  • 李思佳, 王森怡, 李凌晖, 涂迎盈, 蒋曙光*
作者信息 +

Development of Oral Solid Formulation for Insoluble Drugs Based on PASD Technology

  • LI Si-jia, WANG Sen-yi, LI Ling-hui, TU Ying-ying, JIANG Shu-guang*
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摘要

水难溶性是大部分药理活性成分难以开发成口服固体制剂的主要原因。聚合物无定形固体分散体(polymeric amorphous solid dispersion,PASD)能大大提高难溶性药物的表观溶解度及溶出速率,已经成为提高难溶性药物口服生物利用度的常用手段。然而由于PASD中药物处于高表面自由能的无定形态,在储存过程和溶出过程中易于向晶态药物转变从而丧失相应制剂优势。笔者从PASD的处方角度和制备技术角度,为研制质量稳定且后期开发风险低的PASD制剂提供结构化开发思路,并通过分析PASD的上市产品和专利趋势阐述了PASD技术在提高难溶性药物口服固体制剂生物利用度上的应用前景。

Abstract

The low aqueous solubility is the main reason that for most pharmacological active ingredients are challengeable to develop into oral solid formulation. Polymeric amorphous solid dispersion(PASD) can greatly improve the apparent solubility and dissolution rate of poorly soluble drugs, has become a common technology to improve the oral bioavailability of poorly soluble drugs. However, due to the amorphous form of the drug at a high surface free energy in PASD, crystallization would occur during storage and dissolution, thereby losing its formulation advantages. The review attempts to provide a structural development approach of PASD products from the aspects of formulation and technology, in order to guide the development of stable and commercially viable PASD formulations. And the trend analysis of marketed products and patents of PASD will be discussed to understand the prospects of PASD's application in improving the bioavailability of poorly soluble oral solid formulations.

关键词

聚合物无定形固体分散体 / 稳定性 / 混溶性 / 口服固体制剂 / 制剂开发

Key words

polymeric amorphous solid dispersion / stability / miscibility / oral solid formulation / formulation development

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李思佳, 王森怡, 李凌晖, 涂迎盈, 蒋曙光. 基于聚合物无定形固体分散体技术的难溶性药物口服固体制剂开发[J]. 中国药学杂志, 2020, 55(3): 169-176 https://doi.org/10.11669/cpj.2020.03.001
LI Si-jia, WANG Sen-yi, LI Ling-hui, TU Ying-ying, JIANG Shu-guang. Development of Oral Solid Formulation for Insoluble Drugs Based on PASD Technology[J]. Chinese Pharmaceutical Journal, 2020, 55(3): 169-176 https://doi.org/10.11669/cpj.2020.03.001
中图分类号： R944   

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