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Drug–Drug Coamorphous Systems: Characterization and Physicochemical Properties of Coamorphous Atorvastatin with Carvedilol and Glibenclamide

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Abstract

Purpose

In this study, coamorphous form of atorvastatin calcium (ATC) with two drugs, i.e., carvedilol (CVD) and glibenclamide (GLN) in 1:1 stoichiometry, were prepared from solvent evaporation method and they were characterized and their physicochemical properties determined.

Methods

The coamorphous forms were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD). The kinetic solubility of coamorphous form of ATC with CVD (ATC–CVD) and GLN (ATC–GLN) were determined along with stability of supersaturated state of coamorphous forms using developed accurate and precise UV-net analyte signal standard addition method (chemometrics-based approach) and HPLC.

Results

The results of DSC and analysis of glass transition temperatures (T g), PXRD, and FT-IR indicated that the crystalline studied drugs were converted to coamorphous forms, with unique thermal behaviors, revealing a molecular interaction between two components. The kinetic solubility data revealed that coamorphous forms have better metastable solubility than those of crystalline state. In addition, these systems showed greater solution stability than those for amorphous form of single components reported in the literature.

Conclusion

Coamorphous ATC–CVD and ATC–GLN were shown to have improved physicochemical and solution stability properties as compared to crystalline components.

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Acknowledgments

This article is a part of the results of the PhD thesis No. 64 submitted to the Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. The authors would like to thank PXRD lab, Institute of Mineralogy, North Western Regional Office, Tabriz, Iran for providing PXRD patterns, Dr. Karim Asadpour-Zeynali from Faculty of Chemistry, University of Tabriz and Dr. Yousef Javadzadeh from Faculty of Pharmacy, Tabriz University of Medical Sciences for their helps in this study and Gifting the GLN powder by Kimidaru Pharmaceutical Company.

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Authors and Affiliations

  1. Faculty of Pharmacy, Student’s Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Shayanfar

  2. Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Abolghasem Jouyban

  3. Pharmaceutical Engineering Laboratory, School of Chemical Engineering, College of Engineering, University of Tehran, P.O. Box 11155/4563, Tehran, Iran

    Abolghasem Jouyban

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  1. Ali Shayanfar
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Correspondence to Abolghasem Jouyban.

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Shayanfar, A., Jouyban, A. Drug–Drug Coamorphous Systems: Characterization and Physicochemical Properties of Coamorphous Atorvastatin with Carvedilol and Glibenclamide. J Pharm Innov 8, 218–228 (2013). https://doi.org/10.1007/s12247-013-9162-1

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