Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza, 12582, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Drug Deliv Transl Res. 2023 Sep;13(9):2340-2352. doi: 10.1007/s13346-023-01316-9. Epub 2023 Mar 20.
The solid dispersion technique is the most effective and widely used approach for increasing the solubility and release of drugs that have low water solubility. Mirtazapine (MRT) is an atypical antidepressant used to treat severe depression. MRT has a low oral bioavailability (about 50%) due to its low water solubility (BCS class II). The study's goal was to determine optimum conditions for incorporating MRT into various polymer types utilizing the solid dispersion (SD) technique, with the goal of selecting the most suitable formula with the optimal aqueous solubility, loading efficiency, and dissolution rate. The D-optimal design was used to pick the optimal response. The optimum formula was subjected to physicochemical evaluation by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In vivo bioavailability study was conducted on white rabbits' plasma samples. MRT-SDs were prepared by the solvent evaporation method using Eudragit (RL-100, RS-100, E-100, L-100-55), PVP K-30, and PEG 4000 with different drug/polymer percentages (33.33%, 49.99%, and 66.66%). Results showed that the optimum formula obtained using PVP K-30 at a drug percentage of 33.33% gave a loading efficiency of 100.93%, an aqueous solubility of 0.145 mg/ml, and a dissolution rate of 98.12% after 30 min. These findings demonstrated promising enhancement of MRT properties and increasing its oral bioavailability by 1.34-fold more than plain drug.
固体分散体技术是提高水溶性差药物的溶解度和释放度最有效和广泛应用的方法。米氮平(MRT)是一种用于治疗严重抑郁症的非典型抗抑郁药。由于其低水溶性(BCS 分类 II),MRT 的口服生物利用度较低(约 50%)。本研究的目的是利用固体分散(SD)技术确定将 MRT 纳入各种聚合物类型的最佳条件,以选择具有最佳水溶解度、载药量和溶解速率的最合适配方。采用 D-最优设计选择最佳响应。对最优配方进行傅里叶变换红外光谱(FT-IR)、差示扫描量热法(DSC)、X 射线粉末衍射(XRPD)和扫描电子显微镜(SEM)的物理化学评价。在白兔的血浆样品上进行了体内生物利用度研究。采用溶剂蒸发法制备米氮平-SD,使用不同药物/聚合物比例(33.33%、49.99%和 66.66%)的 Eudragit(RL-100、RS-100、E-100、L-100-55)、PVP K-30 和 PEG 4000。结果表明,使用 PVP K-30 时,药物比例为 33.33%的最优配方的载药量为 100.93%,水溶解度为 0.145mg/ml,30min 后溶解率为 98.12%。这些结果表明,通过将 MRT 的性质得到了显著改善,其口服生物利用度提高了 1.34 倍,超过了普通药物。