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Inhibition of Co-Crystallization of Olmesartan Medoxomil and Hydrochlorothiazide for Enhanced Dissolution Rate in Their Fixed Dose Combination

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Abstract

Olmesartan medoxomil (Olm) and hydrochlorothiazide (HCTZ) are fixed dose combination (FDC) for treatment of hypertension. They have hydrogen bonding sites and may interact during co-processing. The consequences of such interaction are not clear. This study investigated the possibility of this interaction during co-processing. The research was extended to inhibit deleterious interactions. The drugs were co-evaporated from ethanolic solution to maximize the chance of interaction. This was performed in the absence and presence of hydroxypropyl methylcellulose (HPMC) and/or aerosil. The products were characterized using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis, and powder X-ray diffraction (PXRD) in addition to dissolution studies. Co-evaporation of Olm with HCTZ in the absence of excipients produced crystalline material with FTIR spectrum showing intermolecular hydrogen bonding. This material showed thermal pattern of new crystalline species. This was identified as Olm/HCTZ co-crystal by PXRD. This co-crystallization reduced the dissolution rate of both drugs. This co-crystallization was inhibited in the presence of HPMC, but the dissolution rate was not significantly enhanced accordingly. Co-processing in the presence of both HPMC and aerosil eliminated the co-crystallization and minimized the intermolecular drug-drug interaction with subsequent dissolution enhancement. The study introduced a composition for fixed dose combination of Olm and HCTZ with enhanced dissolution.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. Department of Pharmaceutical Technology, College of Pharmacy, Tanta University, Tanta, Egypt

    Magdy M. Abdelquader, Ebtessam A. Essa & Gamal M. El Maghraby

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  1. Magdy M. Abdelquader
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Correspondence to Gamal M. El Maghraby.

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Abdelquader, M.M., Essa, E.A. & El Maghraby, G.M. Inhibition of Co-Crystallization of Olmesartan Medoxomil and Hydrochlorothiazide for Enhanced Dissolution Rate in Their Fixed Dose Combination. AAPS PharmSciTech 20, 3 (2019). https://doi.org/10.1208/s12249-018-1207-9

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