Dissolution-permeation of hot-melt extruded amorphous solid dispersion comprising an experimental grade of HPMCAS

Background and purpose: Physicochemical properties of an amorphous solid dispersion (ASD) comprising an experimental grade of hydroxypropyl methylcellulose acetate succinate (HPMCAS-MX) with lower glass transition temperature have been previously investigated. This study aimed to evaluate applicability of HPMCAS-MX to hot-melt extrusion (HME) and dissolution-permeation performance of prepared ASDs using MicroFLUX.

Review approach: A physical mixture of indomethacin (IMC) and HPMCAS-MX or -MG (a commercial grade with higher transition temperature) at 20:80 weight ratio was hot-melt extruded to prepare an ASD (IMC-MX and IMC-MG, respectively). The dissolution-permeation performance and the stability of the ASDs were measured.

Key results: A torque reduction at 120 °C implied that IMC-MX transformed into an amorphous state at this temperature, but IMC-MG required around 170 °C. This result was supported by Raman mapping of the the HME samples. IMC-MG and IMC-MX remained in an amorphous state at 40 °C for three months. The initial dissolution rate and solubility of the ASDs were higher than that of crystalline IMC. The apparent permeability of IMC from IMC-MX and IMC-MG was comparable but was approximately two-fold higher than that from crystalline IMC.

Conclusion: HPMCAS-MX enabled HME process at a lower temperature and improved the dissolution-permeation performance of indomethacin.

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Materials

Indomethacin was purchased from Kongo Chemical Co., Ltd. (Toyama, Japan). A commercial grade of
HPMCAS “Shin-Etsu AQOAT® type MG” and an experimental grade “type MX” originally developed were
kindly gifted by Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan) [19]. GIT-0 lipid (20 wt.% phospholipid dissolved
into dodecane), Prisma HT buffer (pH 6.5), and acceptor sink buffer (ASB) were purchased from pION Inc.
(MA, USA).

Tanaka, H., Miyano, T., & Ueda, H. (2023). Dissolution-permeation of hot-melt extruded amorphous solid dispersion comprising an experimental grade of HPMCAS. ADMET and DMPK. https://doi.org/10.5599/admet.1586

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