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AAPS PharmSciTech

, 20:144 | Cite as

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

  • Jorge Cruz-Angeles
  • Marcelo Videa
  • Luz María MartínezEmail author
Research Article
  • 98 Downloads

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.

KEY WORDS

irbesartan glimepiride metabolic syndrome co-amorphous diabetes hypertension 

Notes

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 Information

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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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.School of Engineering and ScienceTecnologico de MonterreyMonterreyMexico
  2. 2.Department of Sciences: Chemistry and NanotechnologyTecnologico de MonterreyMonterreyMexico

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