Applied Chemistry Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India.
Department of Pharmacology and Pharmacy Practice, Maliba Pharmacy College, Uka Tarsadia University, Bardoli, 394350, Gujarat, India.
AAPS PharmSciTech. 2023 Oct 17;24(8):213. doi: 10.1208/s12249-023-02659-9.
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.
具有显著药学优势的抗糖尿病药物格列吡嗪（GLN），但其水溶性差限制了其广泛应用。本工作旨在开发由 SA-F127 和 TPGS 组成的混合聚合物胶束系统，以提高 GLN 的水溶性和有效传递。首先，我们通过 FTIR、NMR 和 GPC 技术合成了 SA-F127，并对其进行了确认。采用薄膜技术制备 GLN-PMM，并通过 CCD 设计进行优化。采用 DLS、Zeta、TEM、流变学、FTIR、DSC 和 XRD 测量对所开发的 GLN-PMM 进行了表征。GLN-PMM 呈球形形态，粒径为 67.86nm，Zeta 电位为-3.85mV，PDI 值为 0.582±0.06。聚合物混合胶束与 GLN 具有出色的相容性，且在本质上为无定形。NMR 研究证实 GLN 被包封在混合胶束的核心中。此外，还对 GLN-PMM 进行了体外累积药物释放、离体渗透和体内抗糖尿病研究。在不同 pH 环境下，GLN-PMM 的释放曲线在 24 小时后超过 90%，表明具有持续释放的特性。与游离 GLN 相比，GLN-PMM 胶束使山羊肠内 GLN 的渗透度提高了 88.86±3.39%。体内抗糖尿病研究证明，与市售制剂相比，GLN-PMM 聚合物混合胶束具有强大的抗糖尿病作用。这些发现表明，SA-F127 和 TPGS 的聚合物混合胶束可能是一种有前途的、有效的、环保的 GLN 口服传递方法。
