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Design, Development, and Evaluation of SA-F127:TPGS Polymeric Mixed Micelles for Improved Delivery of Glipizide Drug: In-vitro, Ex-vivo, and In-vivo Investigations

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Abstract

The anti-diabetic glipizide (GLN) drug has notable pharmaceutical advantages, but poor aqueous solubility restricts its wide applications. The present work was to develop a mixed polymeric micelle system composed of SA-F127 and TPGS to improve the water solubility and effective delivery of the GLN. First, we synthesized SA-F127 and confirmed it through FTIR, NMR, and GPC techniques. The GLN-PMM were fabricated with the thin-film technique and optimized with CCD design. The developed GLN-PMM was characterized using DLS, Zeta, TEM, Rheology, FTIR, DSC, and XRD measurements. The GLN-PMM manifested a spherical morphology with 67.86 nm particle size, a −3.85 mV zeta potential, and a 0.582±0.06 PDI value. The polymeric mixed micelles showed excellent compatibility with GLN and were amorphous in nature. NMR studies confirmed the encapsulation of GLN in the core of the mixed micelle. In addition, the GLN-PMM micelles were tested in vitro for cumulative drug release, ex vivo for permeation, and in vivo for anti-diabetic investigations. The GLN-PMM release profile in the various pH environments showed over 90% after 24 h, clearly indicating sustained release. The GLN-PMM micelles gave higher 88.86±3.39% GLN permeation from the goat intestine compared with free GLN. In-vivo anti-diabetic investigation proves the powerful anti-diabetic properties of GLN-PMM in comparison to the marketed formulation. These findings demonstrated that the polymeric mixed micelles of SA-F127 and TPGS could be a promising, effective, and environment-friendly approach for oral delivery of the GLN.

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Acknowledgements

Fluorescence measurements were carried out on the instrument purchased under the DST-PURSE program (SR/PURSE Phase 2/28 (C)). XRD measurements were acquired on the instrument purchased under the DST-FIST Program of the Applied Physics Department (SR/FST/PS-II/2017/20). This work was financially supported by the SHODH-Scheme of Developing High-quality Research, Education Department, Gujarat, India. The corresponding author also acknowledged the CoE of Polymers, Applied Chemistry Department, Faculty of Technology and Engineering, for necessary lab facilities.

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Authors and Affiliations

  1. Applied Chemistry Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India

    Hemil S. Patel & Rakesh K. Sharma

  2. Department of Pharmacology and Pharmacy Practice, Maliba Pharmacy College, Uka Tarsadia University, Bardoli, 394350, Gujarat, India

    Bhavin A. Vyas

  3. Department of Chemistry, GLA University, Mathura, 281406, Uttar Pradesh, India

    Subhash Tripathi

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  1. Hemil S. Patel
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Contributions

Hemil S Patel: investigation; methodology; data analysis; writing – original draft; software; artwork.

Rakesh K Sharma: conceptualization; supervision; project administration; writing – original draft; review and editing.

Subhash Tripathi: methodology, artwork.

Bhavin A. Vyas: carried out in-vivo anti-diabetic study.

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Correspondence to Rakesh K. Sharma.

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The Animal study protocol was approved by The Institutional Animal Ethics Committee (Maliba Pharmacy College, Uka Tarsadiya University, Bardoli Gujarat, India) No. MPC/IAEC/19/2021).

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Patel, H.S., Vyas, B.A., Tripathi, S. et al. Design, Development, and Evaluation of SA-F127:TPGS Polymeric Mixed Micelles for Improved Delivery of Glipizide Drug: In-vitro, Ex-vivo, and In-vivo Investigations. AAPS PharmSciTech 24, 213 (2023). https://doi.org/10.1208/s12249-023-02659-9

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