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Inclusion Complex of Ibuprofen-β-Cyclodextrin Incorporated in Gel for Mucosal Delivery: Optimization Using an Experimental Design

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Abstract

β-Cyclodextrin/ibuprofen inclusion complex was synthesized by freeze-drying method and characterized for phase solubility profiles, infrared spectra, thermal analysis, and X-ray powder diffractograms. The inclusion complex with HP-β-CD, as confirmed by molecular dynamics simulations, enhanced the aqueous solubility of ibuprofen by almost 30-fold compared to ibuprofen alone. Different grades of Carbopol (Carbopol 934P/Carbopol 974P/Carbopol 980 NF/Carbopol Ultrez 10 NF) and cellulose derivatives (HPMC K100M/HPMC K15M/HPMC K4M/HPMC E15LV/HPC) were evaluated for mucoadhesive gels incorporating the inclusion complex. The central composite design generated by Design-Expert was employed to optimize the mucoadhesive gel using two independent variables (a varying combination of two gelling agents) on three dependent variables (drug content and in vitro drug release at 6 h and 12 h). Except for the methylcellulose-based gels, most of the gels (0.5%, 0.75%, and 1% alone or as a mixture thereof) exhibited an extended-release of ibuprofen, ranging from 40 to 74% over 24 h and followed the Korsmeyer-Peppas kinetics model. Using this test design, 0.95% Carbopol 934P and 0.55% HPC-L formulations were optimized to increase ibuprofen release, enhance mucoadhesion, and be non-irritating in ex vivo chorioallantoic membrane studies. The present study successfully developed a mucoadhesive gel containing the ibuprofen-β-cyclodextrin inclusion complex with sustained release.

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Acknowledgements

The authors would also like to thank IOL Chemicals and Pharmaceuticals Limited, Ludhiana, India, for ibuprofen, Lubrizol Corporation, USA, for different grades of carbopols and Colorcon Asia Pvt. Limited, India, for different grades of HPMC. Authors are thankful to B.N. University, Udaipur, Rajasthan, for providing necessary financial support.

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Authors and Affiliations

  1. B.N Institute of Pharmaceutical Sciences, B. N. University, Udaipur, Rajasthan, India

    Chandraprabha Upadhyay & Meenakshi Bharkatiya

  2. School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania, USA

    Anisha D’Souza

  3. Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland

    Pratikkumar Patel & Vivek Verma

  4. Pharma R&D, Biological E LTD, Hyderabad, India

    Kamal Kumar Upadhayay

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  1. Chandraprabha Upadhyay
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Methodology, experiments, writing (original draft), CU; editing and review, PP, AD, and KKU; in silico work, VV; writing review, editing, and supervision, Meenakshi Bharkatiya.

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Upadhyay, C., D’Souza, A., Patel, P. et al. Inclusion Complex of Ibuprofen-β-Cyclodextrin Incorporated in Gel for Mucosal Delivery: Optimization Using an Experimental Design. AAPS PharmSciTech 24, 100 (2023). https://doi.org/10.1208/s12249-023-02534-7

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