Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka State, 576106, India.
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka State, 576104, India.
AAPS PharmSciTech. 2022 Oct 17;23(8):284. doi: 10.1208/s12249-022-02437-z.
The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology.
本研究旨在研究亲水性载体如聚乙二醇 1500 和 PEG-50 氢化蓖麻油（Acconon）的固体分散体（SD）中，难溶性格列本脲（GLB）的混溶性、物理稳定性、溶解度和溶出速率。利用 Hansen 溶解度参数、Flory Huggins 理论、吉布斯自由能等数学理论以及计算机分子动力学模拟研究方法来预测药物载体的混溶性。为了进一步提高溶解度，将泡腾技术引入常规固体分散体中，制备泡腾固体分散体（ESD）。通过微波、溶剂蒸发、冷冻干燥和热熔挤出（HME）技术制备固体分散体（SD），并测试了不同的特征参数。理论和计算机参数表明，在某些条件下，GLB 将与所选载体具有良好的混溶性。傅里叶变换红外光谱和质子核磁共振光谱证实了药物和载体之间的分子间氢键。粉末 X 射线衍射、差示扫描量热法和显微镜等固态特性证实了 SD 的无定形性质。由于添加了泡腾剂提高了无定形性质，因此溶解度和药物释放速率得到了提高。体外和肠内吸收研究表明，通量和渗透性均高于纯药物，提示药物传递得到增强。SD 和 ESD 技术大大提高了 GLB 的溶解度、溶解和稳定性。
