Dual-drug amorphous formulation of gliclazide
Aljohani, Marwah McArdle, Patrick Erxleben, Andrea
Aljohani, Marwah
McArdle, Patrick
Erxleben, Andrea
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Publication Date
2021-02-01
Type
Article
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Aljohani, Marwah, McArdle, Patrick, & Erxleben, Andrea. (2021). Dual-drug amorphous formulation of gliclazide. Drug Development and Industrial Pharmacy, 47(2), 302-307. doi:10.1080/03639045.2021.1879838
Abstract
Amorphization is a well-established strategy to enhance the dissolution properties of poorly water-soluble drugs. However, the amorphous state is inherently unstable toward recrystallization. Coamorphous systems of a drug and a small-molecule excipient or of two complementary drugs often show an enhanced stability. Diabetes and hypertension are frequently coexistent. In this paper a study on the coamorphization of the poorly water-soluble antidiabetic drug gliclazide (glz) and the antihypertensive drug valsartan (val) is reported. Amorphous glz recrystallized after 1 d under ambient conditions, whereas coamorphous glz-val containing glz and val in a 1:1 or 1:2 molar ratio was stable for at least four months at 20 °C and 56% relative humidity. The dissolution rate of glz increased in the order crystalline glz < glz-val_1:1 < glz-val_1:2. Furthermore, ternary coamorphous systems of glz, val and an excipient were prepared; glz-val_1:1_PVP, glz-val_1:1_HPC, glz-val_1:1_ALM, glz-val_1:1_MCC (PVP = polyvinylpyrrolidone, HPC = hydroxypropyl cellulose, ALM = α-lactose monohydrate, MCC = microcrystalline cellulose). MCC and HPC did not affect the stability of the coamorphous system, while ALM promoted the recrystallization of glz in glz-val_1:1_ALM during storage and freshly prepared glz-val_1:1_PVP contained small amounts of crystalline glz. Glz-val_1:1_MCC showed enhanced dissolution properties compared to crystalline glz and glz-val_1:1 and is a viable fixed-dose formulation.
Publisher
Taylor and Francis
Publisher DOI
10.1080/03639045.2021.1879838
Rights
Attribution 4.0 International (CC BY 4.0)