Fraunhofer Institute for Molecular Biology and Applied Ecology, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany; Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany.
Fraunhofer Institute for Molecular Biology and Applied Ecology, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany.
Eur J Pharm Biopharm. 2019 Jan;134:144-152. doi: 10.1016/j.ejpb.2018.11.012. Epub 2018 Nov 16.
Since many drugs in the therapy scheme of multiple sclerosis (MS) are applied parenterally with significant side effects, oral treatment is the most accepted therapy option for chronic diseases like MS. The drug candidate TMP-001, which has disease-modifying properties, can be applied orally. Beside other symptoms, swallowing disorders have a major impact not only on the health status and quality of life of MS patients, but also impede reliable drug therapy. Consequently, the development of an easy-to-swallow liquid oral dosage form supported by a combined PBPK-IVIVC model was approached. In this context, the impact of formulation parameters was studied. Biorelevant in vitro drug release studies resulted in an almost complete release of 96.91% ± 1.00% in the intestine which was translated to rapidly increasing in silico plasma profiles. The predictions were compared to the outcome of a phase I clinical trial. A partial parameter sensitivity analysis of the in silico model deepened our understanding of the physiological processes underlying human pharmacokinetics.
由于多发性硬化症 (MS) 治疗方案中的许多药物都有明显的副作用，需要通过注射给药，因此口服治疗是 MS 等慢性疾病最被接受的治疗选择。候选药物 TMP-001 具有疾病修饰特性，可以口服给药。除其他症状外，吞咽障碍不仅对 MS 患者的健康状况和生活质量有重大影响，还会阻碍可靠的药物治疗。因此，研究人员开发了一种易于吞咽的口服液体剂型，并辅以组合的 PBPK-IVIVC 模型。在这方面，研究了配方参数的影响。生物相关性体外药物释放研究导致在肠道中几乎完全释放 96.91%±1.00%，这转化为快速增加的体内血浆曲线。预测结果与 I 期临床试验的结果进行了比较。对体内模型的部分参数敏感性分析加深了我们对人体药代动力学中生理过程的理解。
