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Development and statistical optimization of chitosan and eudragit based gastroretentive controlled release multiparticulate system for bioavailability enhancement of metformin HCl

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Abstract

The present research was intended to develop a gastroretentive controlled release multiparticulate delivery system for a hypoglycemic drug, metformin hydrochloride (MTF) that could efficiently deliver the drug in active form and also increase its systemic bioavailability. In vitro and in vivo evaluations were performed to determine the efficacy of the formulation. MTF loaded microspheres were prepared by W/O/O double emulsion-solvent evaporation method and optimized by 32 full factorial design. The ratio of eudragit RL100 & RS100 (EL:ES) and the chitosan concentration were evaluated as independent variables for dependent variables viz. percent drug release (%DR), percent yield (%Y) and encapsulation efficiency (EE). The morphological characteristics of the microspheres were assessed using scanning electron microscopy which revealed non-aggregated, spherical shape microspheres with rough and rugged surfaces. The particle size range of the formulated microspheres was found to be ~74.77–111.18 µm. In vitro drug release best fitted Korsmeyer Peppas release characteristics with Fickian diffusion release mechanism. The optimized batch F1 demonstrated 84.17 ± 5.80 % drug release, 85.47 ± 0.28 % yield and 70.79 ± 0.67 % EE. Optimized batch performed superior pharmacokinetics with prolonged and increased intensity of hypoglycemic effect (87.68 ± 4.9 %) a relative bioavailability of 154.71 % with respect to the marketed product (56.67 ± 4.7 %). These findings highlight the potential of formulated microparticles as a superior candidate for gastro-retentive sustained release delivery of MTF with respect to marketed product.

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Acknowledgments

All authors (A. K. Sahu, A. Verma) declare that they have no conflict of interest. The authors would like to acknowledge Production Manager, Harman Finochem Ltd., India, Evonik Pharma Polymers GmbH, Mumbai, and Central Institute of Fisheries Technology, Kochi for providing gift samples. Special thanks to Principal, VNS Institute of Pharmacy, Bhopal for availing the permissions and required facilities to carry out in vivo studies. We extend our gratitude to the staff members of Department of Pharmacy, SHIATS, Allahabad.

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  1. Shambhunath Institute of Pharmacy, Jhalwa, Allahabad, Uttar Pradesh, 211012, India

    Atul Kumar Sahu

  2. Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Sciences, Allahabad, Uttar Pradesh, 211007, India

    Amita Verma

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Sahu, A.K., Verma, A. Development and statistical optimization of chitosan and eudragit based gastroretentive controlled release multiparticulate system for bioavailability enhancement of metformin HCl. Journal of Pharmaceutical Investigation 46, 239–252 (2016). https://doi.org/10.1007/s40005-016-0229-0

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