Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin.

Hiroshi Ueda,Katsuji Sugita,Yuya Hirakawa,Tetsuya Miyano,Hironori Tanaka

doi:10.3390/pharmaceutics13030353

Hiroshi Ueda, Katsuji Sugita + Show 3 more

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https://doi.org/10.3390/pharmaceutics13030353

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Journal: Pharmaceutics	Publication Date: Mar 8, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Futaba (Japan), Shionogi (Japan)

Abstract

The transformation of a crystalline drug into an amorphous form is a promising way to enhance the oral bioavailability of poorly water-soluble drugs. Blending of a carrier, such as a hydrophilic polymer, with an amorphous drug is a widely used method to produce a solid dispersion and inhibit crystallization. This study investigates an experimental grade of hydroxypropyl methylcellulose acetate succinate, HPMCAS-MX (MX), as a solid dispersion carrier. Enhancement of thermal stability and reduction of the glass transition temperature (Tg) of MX compared with those of the conventional grade were evaluated through thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of a homogeneous amorphous solid dispersion between MX and indomethacin was confirmed by X-ray powder diffraction analysis, DSC, and Raman mapping. It was observed that 10–30% MX did not act as an anti-plasticizer, but the utilization of >40% MX caused an increase in Tg and reduction of molecular mobility. This could be explained by a change in intermolecular interactions, inferred from infrared spectroscopy combined with principal component analysis. HPMCAS-MX exhibited similar performance to that of conventional-grade, HPMCAS-MG. Although HPMCAS-MX has thermal properties different from those of conventional-grade HPMCAS-MG, it retains its ability as a solid dispersion carrier.

Highlights

Dosage per oral administration is a conventional pharmaceutical form, a non-invasive route that enables patients to take medicine in a way that is familiar and convenient for both adults and children [1,2,3]
This study aimed to investigate the physicochemical properties of an experimental grade of hydroxypropyl methylcellulose acetate succinate (HPMCAS), which modified the moiety for its commercial grade [33], applied as a solid dispersion carrier
This study investigated the physicochemical properties of an experimental grade of HPMCAS, “HPMCAS-MX”, designed by modification of the functional group of MG/MF

Summary

Introduction

Dosage per oral administration is a conventional pharmaceutical form, a non-invasive route that enables patients to take medicine in a way that is familiar and convenient for both adults and children [1,2,3]. Drug discovery and development of small molecules for simple oral administration is important and accounted for over half of the drugs approved in 2019 [7]. Development, and manufacture of drugs, one of the most critical issues for oral absorption is an increase in poorly water-soluble small molecules, because drugs are absorbed by penetration through gastrointestinal membrane following their dissolution into the gastrointestinal fluids [8]. To overcome this issue, the conversion of the crystal form and the design of formulations to enhance drug solubility have been widely investigated [8].

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