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醋酸羟丙甲纤维素琥珀酸酯在干法包衣工艺中的溶解度参数及增塑作用

Solubility parameters of hypromellose acetate succinate and plasticization in dry coating procedures.

作者信息

Klar Fabian, Urbanetz Nora Anne

机构信息

a Flurepha, Division of Pharmaceutics , Gelsenkirchen , Germany ;

b Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine University , Duesseldorf , Germany ;

出版信息

Drug Dev Ind Pharm. 2016 Oct;42(10):1621-35. doi: 10.3109/03639045.2016.1160106. Epub 2016 Mar 22.

Abstract

Solubility parameters of HPMCAS have not yet been investigated intensively. On this account, total and three-dimensional solubility parameters of HPMCAS were determined by using different experimental as well as computational methods. In addition, solubility properties of HPMCAS in a huge number of solvents were tested and a Teas plot for HPMCAS was created. The total solubility parameter of about 24 MPa(0.5) was confirmed by various procedures and compared with values of plasticizers. Twenty common pharmaceutical plasticizers were evaluated in terms of their suitability for supporting film formation of HPMCAS under dry coating conditions. Therefore, glass transition temperatures of mixtures of polymer and plasticizers were inspected and film formation of potential ones was further investigated in dry coating of pellets. Contact angles of plasticizers on HPMCAS were determined in order to give a hint of achievable coating efficiencies in dry coating, but none was found to spread on HPMCAS. A few common substances, e.g. dimethyl phthalate, glycerol monocaprylate, and polyethylene glycol 400, enabled plasticization of HPMCAS; however, only triethyl citrate and triacetin were found to be suitable for use in dry coating. Addition of acetylated monoglycerides to triacetin increased coating efficiency, which was likewise previously demonstrated for triethyl citrate.

摘要

羟丙甲纤维素醋酸琥珀酸酯(HPMCAS)的溶解度参数尚未得到深入研究。基于此,采用不同的实验和计算方法测定了HPMCAS的总溶解度参数和三维溶解度参数。此外,测试了HPMCAS在大量溶剂中的溶解性能,并绘制了HPMCAS的Teas图。通过各种方法确定了约24 MPa(0.5)的总溶解度参数,并与增塑剂的值进行了比较。评估了20种常见药用增塑剂在干包衣条件下对HPMCAS成膜的适用性。因此,考察了聚合物与增塑剂混合物的玻璃化转变温度,并在微丸干包衣中进一步研究了潜在增塑剂的成膜情况。测定了增塑剂在HPMCAS上的接触角,以提示干包衣中可实现的包衣效率,但未发现有增塑剂能在HPMCAS上铺展。一些常见物质,如邻苯二甲酸二甲酯、单辛酸甘油酯和聚乙二醇400,能够使HPMCAS增塑;然而,仅发现柠檬酸三乙酯和三醋精适用于干包衣。向三醋精中添加乙酰化单甘油酯可提高包衣效率,这同样在柠檬酸三乙酯中得到过证实。

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