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Glibenclamide Nanocrystals for Bioavailability Enhancement: Formulation Design, Process Optimization, and Pharmacodynamic Evaluation

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Abstract

The aim of this study is to improve the bioavailability of a poorly water-soluble drug glibenclamide (GLB), by preparing drug nanocrystals using wet milling by zirconia beads. To improve the dissolution characteristics, various formulation and process variables were identified and optimized by employing a 32 factorial design at two stages. Based on preliminary studies, the formulation variables selected were polymer-to-drug ratio and surfactant-to-drug ratio and the process variables selected were milling speed and milling time. The particle size, zeta potential, saturation solubility, and percentage drug released at 10 min were selected as dependent variables at both stages. F ratio suggested that the predetermined response parameters were significantly dependent on the independent variables. An optimum desirability of 0.9925 was achieved using response profiler by Statistica® 8.0. The optimized formulation prepared as per levels obtained through desirability showed a close agreement between the predicted and expected values. X-ray diffraction studies concluded that the crystallinity of prepared nanocrystals was intact and the increased dissolution could be ascribed to conversion of unmilled drug to nanocrystals. In vivo studies carried out on male Wistar rats suggested a higher AUEC(0–8h) for GLB nanocrystals as compared to pure GLB which could be ascribed to significant improvement of release from GLB nanocrystals as compared to pure GLB. It could be concluded that prepared GLB nanocrystals showed better bioavailability as compared to pure GLB and could offer improved drug therapy.

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Acknowledgments

The authors are thankful to Cadila Pharmaceuticals Limited, International Speciality Products, for providing the respective gift samples.

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Bhagvanlal Kapoorchand Mody Government Pharmacy College, Rajkot, India

    Sunny R. Shah

  2. Ramanbhai Patel College of Pharmacy, CHARUSAT, Changa, India

    Rajesh H. Parikh

  3. Bhagvanlal Kapoorchand Mody Government Pharmacy College, Rajkot, India

    Jayant R. Chavda

  4. Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, India

    Navin R. Sheth

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  1. Sunny R. Shah
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  2. Rajesh H. Parikh
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  3. Jayant R. Chavda
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  4. Navin R. Sheth
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Correspondence to Sunny R. Shah.

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Shah, S.R., Parikh, R.H., Chavda, J.R. et al. Glibenclamide Nanocrystals for Bioavailability Enhancement: Formulation Design, Process Optimization, and Pharmacodynamic Evaluation. J Pharm Innov 9, 227–237 (2014). https://doi.org/10.1007/s12247-014-9189-y

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  • DOI: https://doi.org/10.1007/s12247-014-9189-y

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