ROFEL Shri G.M. Bilakhia College of Pharmacy, Vapi, Gujarat, 396191, India.
AAPS PharmSciTech. 2021 Dec 14;23(1):20. doi: 10.1208/s12249-021-02172-x.
Zotepine is an atypical antipsychotic drug used in the treatment of schizophrenia. However, its poor dissolution properties limit its therapeutic efficacy. In this investigation, a series of nanosuspension-containing zotepine were prepared employing media milling method with an aim to improve its dissolution properties and oral bioavailability. Briefly, Box-Behnken design was applied to investigate the influence of various independent variables such as X- amount of stabilizer, X- amount of milling agent, and X- milling time on the performance of the formulation. Dissolution studies revealed enhancement of dissolution rate as compared to pure drug. Solid state characterization (DSC, PXRD, and SEM) studies demonstrated no polymorphic changes in drug after lyophilization of media-milled nanosuspension. In vivo pharmacokinetic studies of lyophilized nanosuspension was carried out in rat and the results exhibited significant improvement in C and AUC, about 450.0 and 287.45%, respectively, suggesting amelioration in oral bioavailability by 2.87-fold higher as compared to pure drug. Accelerated stability studies of the optimized lyophilized formulation at 40°C and 75% RH suggested stability of the nanocrystals for at least a 6-month period. The obtained nanocrystals successfully showed dissolution enhancement and improved oral bioavailability of poorly water-soluble drug, zotepine.
佐替平是一种用于治疗精神分裂症的非典型抗精神病药物。然而，其较差的溶解性能限制了其治疗效果。在这项研究中，采用介质研磨法制备了一系列包含纳米混悬剂的佐替平，旨在提高其溶解性能和口服生物利用度。简要地说，采用 Box-Behnken 设计考察了各种独立变量（如 X-稳定剂用量、X-研磨剂用量和 X-研磨时间）对制剂性能的影响。溶出度研究表明，与纯药物相比，溶出速率得到了提高。固态表征（DSC、PXRD 和 SEM）研究表明，药物在介质研磨纳米混悬液冷冻干燥后没有发生多晶型变化。在大鼠中进行了冻干纳米混悬液的体内药代动力学研究，结果表明 C 和 AUC 分别显著提高了约 450.0 和 287.45%，表明与纯药物相比，口服生物利用度提高了 2.87 倍。在 40°C 和 75% RH 下对优化的冻干制剂进行加速稳定性研究表明，纳米晶至少在 6 个月内稳定。所得纳米晶体成功地显示出了对难溶性药物佐替平的溶解增强和口服生物利用度的提高。
