Glibenclamide co-crystals: Development and characterization using D-mannitol and citric acid as a carrier to improve its dissolution profile

Year 2025, Volume: 29 Issue: 5, 2023 - 2034, 01.09.2025

Sukmarini Anugrahanti Nindya Kusumorini Adhyatmika Adhyatmika

https://doi.org/10.12991/jrespharm.1766172

Abstract

Recent studies have focused on improving the dissolution profile of drugs classified as Biopharmaceutical Classification System (BCS) Class II by utilizing porous particles. Porous particles such as mesoporous mannitol have demonstrated efficacy in improving the dissolution profile of BCS Class II drugs. The current study aims to enhance the dissolution profile of glibenclamide, characterized by low solubility in water (4 mg/L), using the co-crystallization method facilitated by porous particles of mesoporous mannitol. Mesoporous mannitol is prepared from 15% w/v D-mannitol with 2% w/v citric acid, which is then dried using a spray dryer with an inlet temperature of 170° C and outlet temperature of 100° C, respectively. Furthermore, the glibenclamide drug is loaded into mesoporous mannitol using an adsorption method. The study produced mesoporous mannitol with a surface area of 1.944 ± 0.43 m2/g, pore volume of 8.233 x 10-3 ± 0.31 cc/g, and pore size of 162.9 ± 5.66 Å, much higher than D-mannitol. Moreover, the results of co-crystallization of pure glibenclamide with mesoporous mannitol have succeeded in enhancing the dissolution profile by 5.6 times compared to pure glibenclamide and have resulted in changes in the shape of the crystal structure of polymorphous α and β, which occurs due to hydrogen bonding between glibenclamide and mesoporous mannitol.

Keywords

Diabetes mellitus , glibenclamide , co-crystallization , low solubility

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