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Highly Soluble Glimepiride and Irbesartan Co-amorphous Formulation with Potential Application in Combination Therapy

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Abstract

One-third of the population of the USA suffers from metabolic syndrome (MetS). Treatment of patients with MetS regularly includes drugs prescribed simultaneously to treat diabetes and cardiovascular diseases. Therefore, the development of novel multidrug formulations is recommended. However, the main problem with these drugs is their low solubility. The use of binary co-amorphous systems emerges as a promising strategy to increase drug solubility. In the present study, irbesartan (IBS) and glimepiride (GMP), class II active pharmaceutical ingredients (API), widely used in the treatment of arterial hypertension and diabetes, were selected to develop a novel binary co-amorphous system with remarkable enhancement in the dissolution of both APIs. The phase diagram of IBS–GMP was constructed and co-amorphous systems were prepared by melt-quench, in a wide range of compositions. Dissolution profile (studied at pH 1.2 and 37°C for mole fractions 0.01, 0.1, and 0.5) demonstrated that the xGMP = 0.01 formulation presents the highest enhancement in its dissolution. GMP went from being practically insoluble to reach 3.9 ± 0.9 μg/mL, and IBS showed a 12-fold increment with respect to the dissolution of its crystalline form. Infrared studies showed that the increase in the dissolution profile is related to the intermolecular interactions (hydrogen bonds), which were dependent of composition. Results of structural and thermal characterization performed by XRD and DSC showed that samples have remained in amorphous state for more than 10 months of storage. This work contributes to the development of a highly soluble co-amorphous drugs with potential used in the treatment of MetS.

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Acknowledgments

JCA thanks the scholarships provided by CONACyT (285482). We also thank the Center of Biotechnology and Centro del Agua para América Latina y el Caribe, CAALCA, for access to the HPLC facilities.

Funding

We thank the financial support provided by Secretaría de Eduación Pública y Consejo Nacional de Ciencia y Tecnología (SEP-CONACyT) through the Basic Scientific Research Program (No. 255135), and the School of Engineering and Sciences at Tecnologico de Monterrey and the Research Chair of Emerging Technologies.

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  1. School of Engineering and Science, Tecnologico de Monterrey, Campus Monterrey, Ave. Eugenio Garza Sada 2501 Sur., C.P. 64849, Monterrey, N.L., Mexico

    Jorge Cruz-Angeles, Marcelo Videa & Luz María Martínez

  2. Department of Sciences: Chemistry and Nanotechnology, Tecnologico de Monterrey, Campus Monterrey, Ave. Eugenio Garza Sada 2501 Sur., C.P. 64849, Monterrey, N.L., Mexico

    Marcelo Videa & Luz María Martínez

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  1. Jorge Cruz-Angeles
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Correspondence to Luz María Martínez.

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Cruz-Angeles, J., Videa, M. & Martínez, L.M. Highly Soluble Glimepiride and Irbesartan Co-amorphous Formulation with Potential Application in Combination Therapy. AAPS PharmSciTech 20, 144 (2019). https://doi.org/10.1208/s12249-019-1359-2

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