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基于原子力显微镜的药物-赋形剂固体分散体混合和稳定性筛选。

Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions.

机构信息

Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006 Basel, Switzerland.

出版信息

Pharm Res. 2011 Mar;28(3):572-84. doi: 10.1007/s11095-010-0306-4. Epub 2010 Nov 3.

DOI:10.1007/s11095-010-0306-4
PMID:21046435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3044090/
Abstract

PURPOSE

Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method.

METHODS

Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature.

RESULTS

Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations.

CONCLUSIONS

The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few days.

摘要

目的

开发一种使用熔融混合方法评估固体分散体中药物/聚合物混合和稳定性的方法。

方法

采用拉曼显微镜结合原子力显微镜制备和表征非晶质断裂薄膜，以区分均匀和不均匀混合的药物/聚合物组合。对均匀混合的药物/聚合物组合进行进一步分析，以研究在高湿度或高温等压力条件下的物理稳定性。

结果

确定了具有形成分子弥散混合物潜力的组合。通过分子长度尺度的成像来确定它们的相分离潜力，这导致观察时间短。通过相分离分析对离析进行定量，并对药物/聚合物组合进行排序以确定最稳定的组合。

结论

所呈现的结果表明，原子力显微镜可以分析具有许多机械细节的固体分散体中药物/聚合物的混合和稳定性。该测定法可以在数小时或数天内识别出良好混合和稳定的组合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/001472101e3a/11095_2010_306_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/d0c54bf337b7/11095_2010_306_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/436b8ae80e7e/11095_2010_306_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/9fb799f4c495/11095_2010_306_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/c37cbdc27088/11095_2010_306_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/5b5cbf6f5628/11095_2010_306_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/7b59e37425d7/11095_2010_306_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/044a47c4c874/11095_2010_306_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/001472101e3a/11095_2010_306_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/d0c54bf337b7/11095_2010_306_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/436b8ae80e7e/11095_2010_306_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/9fb799f4c495/11095_2010_306_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/c37cbdc27088/11095_2010_306_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/5b5cbf6f5628/11095_2010_306_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/7b59e37425d7/11095_2010_306_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/044a47c4c874/11095_2010_306_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48a7/3044090/001472101e3a/11095_2010_306_Fig8_HTML.jpg

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