期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 151, 期 -, 页码 9-17出版社
ELSEVIER
DOI: 10.1016/j.ejpb.2020.03.013
关键词
Aspirin; Acetylsalicylic acid; Magenstrasse; Stomach road; Biorelevant dissolution; Food effect; Pharmacokinetic; Fed state
资金
- Bayer HealthCare
The process of gastric emptying is of major importance for the in vivo performance of immediate release dosage forms. In the fed state, this process consists of two phases: the rapid emptying of water along the Magenstrasse and the continuous emptying of the chyme. The relevance of these phases for the pharmacokinetic (PK) profile of a drug depends on the release behavior from its dosage form. It was the aim of this study to investigate the role of gastric emptying for the pharmacokinetics of a fast disintegrating and dissolving Aspirin (R) tablet (FDDT). For this purpose, a three way pharmacokinetic study with 30 healthy volunteers was performed to investigate the performance of the FDDT under fasted and fed conditions and compare it to a regular Aspirin (R) tablet (RT) administered in the fed state. Plasma samples were taken at predetermined time points and analyzed by LC MS/MS. In the second part of this work, both products were tested in a biorelevant dissolution test device - the GastroDuo. To simulate the occurrence of the Magenstrasse at different time points, two test programs have been applied. The results of the PK study clearly demonstrated the superiority of the FDDT over the RT. We observed an earlier tmax (0.39 h vs. 2.00 h) and a higher Cmax (6.33 +/- 2.37 mu g/mL vs. 3.23 +/- 1.28 mu g/mL), whereas the AUC was only slightly different between both formulations. The administration of the FDDT together with food had no marked effect on tmax (0.34 h vs. 0.39 h), but caused a decrease in Cmax compared to fasted intake (14.76 +/- 4.81 mu g/mL vs. 6.33 +/- 2.37 mu g/mL). This effect could be explained by the in vitro data collected with the GastroDuo. The FDDT showed a faster drug release and improved emptying kinetics in the GastroDuo. In contrast, the RT showed incomplete emptying in both test programs. Thus, the early tmax observed for the FDDT under fed conditions could be related to the presence of the Magenstrasse. In contrast, drug release from the RT was insufficient to allow gastric emptying via the Magenstrasse, which resulted in later tmax. This study highlighted the importance of gastric emptying for immediate release dosage forms and illustrated that the application of suitable formulation techniques provides a strategy to generate a fast and reliable onset of drug plasma concentrations even in the fed state.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据