Design and Evaluation of Two-Step Biorelevant Dissolution Methods for Docetaxel Oral Formulations.
Design and Evaluation of Two-Step Biorelevant Dissolution Methods for Docetaxel Oral Formulations.
复制标题
多西他赛口服配方的两步生物溶解方法的设计和评估。
DOI：
10.1208/s12249-022-02256-2
复制
发表时间：
2022-04-19
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
--
作者：
溶出度是口服制剂的关键工具。溶出度可用于通过质量控制降低产品失效的风险，或预测和了解药物制剂的体内性能。后者总是具有挑战性的，因为涉及多种因素，如培养基的选择、胃肠道成分、生理因素、禁食和进食状态的考虑。先前发表的溶出方法，如在单个模拟胃液、模拟肠液或磷酸盐缓冲盐水中的一步溶出，并不意味着真实的胃肠道通过效应。多西他赛（DTX）是一种水溶性差的药物，仅以注射剂型市售，因此许多出版物研究了口服DTX制剂的开发。在我们之前的报告中，我们开发了口服脂质基DTX颗粒，与DTX粉末相比，其在大鼠中显示出更高的口服吸收。但在模拟胃液中的一步溶出度显示，DTX颗粒和DTX粉末之间没有差异。因此，本研究的目的是开发新的两步生物相关的溶出度方法的DTX口服制剂。在这项研究中，开发了空腹或进食状态下使用胰酶的新的两步生物相关溶出方法，并与其他先前报道的溶出方法进行了比较。新的两步生物相关溶出方法成功区分了DTX颗粒和DTX粉末的溶出差异，反映了这两种制剂在体内吸收的差异。此外，还证实了食物对DTX的影响。新的溶出方法有可能用于预测和了解口服固体剂型的体内性能。
Dissolution is a pivotal tool for oral formulations. Dissolution could be used to either reduce the risk of product failure through quality control or predict and understand in vivo performance of drug formulations. The latter is always challenging because multiple factors such as selection of media, gastrointestinal components, physiological factors, consideration of fasted and fed state are involved. Previously published dissolution methods such as one-step dissolution in individual simulated gastric fluid, simulated intestinal fluid, or phosphate buffer saline did not signify the realistic gastrointestinal transit effect. Docetaxel (DTX), a poorly water-soluble drug, is commercially available only as injectable dosage forms, and thus many publications studied the development of oral DTX formulations. In our previous report, we developed oral lipid-based DTX granules that showed higher oral absorption in rats compared to DTX powder. However, one-step dissolution in simulated gastric fluid showed no difference between DTX granules and DTX powder. Therefore, the present study aimed to develop new two-step biorelevant dissolution methods for DTX oral formulations. In the study, new two-step biorelevant dissolution methods in fasted or fed states with pancreatin were developed and compared with other previously reported dissolution methods. The new two-step biorelevant dissolution methods successfully discriminated the difference of dissolution between DTX granules and DTX powder, which reflected the in vivo difference of absorption of these two formulations. Moreover, food effects were confirmed for DTX. The new dissolution methods have the potential to be used to predict and understand in vivo performance of oral solid dosage forms.
登录
查看更多内容
影响因子：
4.9
作者：
Mann, James;Dressman, Jennifer;Butler, James
通讯作者：
Butler, James
影响因子：
4.6
作者：
Ibrahim, Fady;Gershkovich, Pavel;Wasan, Kishor M.
通讯作者：
Wasan, Kishor M.
影响因子：
3.8
作者：
Stillhart, Cordula;Duerr, Desiree;Kuentz, Martin
通讯作者：
Kuentz, Martin
影响因子：
4.6
作者：
Boyd, Ben J.;Bergstrom, Christel A. S.;Jannin, Vincent
通讯作者：
Jannin, Vincent
影响因子：
3.7
作者：
Chen, LR;Wesley, JA;Babu, SR
通讯作者：
Babu, SR