Use of biorelevant media for assessment of a poorly soluble weakly basic drug in the form of liquisolid compacts: in vitro and in vivo study

作者：Badawy Mahmoud A; Kamel Amany O^*; Sammour Omaima A

来源：Drug Delivery, 2016, 23(3): 818-827.

DOI：10.3109/10717544.2014.917442

• Biorelevant media
• in vitro dissolution
• in vivo pharmacokinetics
• liquisolid compacts

The purpose of this work is to use biorelevant media to evaluate the robustness of a poorly water soluble weakly basic drug to variations along the gastrointestinal tract (GIT) after incorporation in liquisolid compacts and to assess the success of these models in predicting the in vivo performance. Liquisolid tablets were prepared using mosapride citrate as a model drug. A factorial design experiment was used to study the effect of three factors, namely: drug concentration at two levels (5% and 10%), carriers at three levels (avicel, mannitol and lactose) and powder excipients ratio (R) of the coating material at two levels (25 and 30). The in vitro dissolution media utilized were 0.1N HCl, hypoacidic stomach model and a transfer model simulating the transfer from the stomach to the intestine. All compacts released above 95% of drug after 10min in 0.1N HCl. In the hypoacidic model, the compacts with R 30 were superior compared to R 25, where they released >90% of drug after 10min compared to 80% for R 25. After the transfer of the optimum compacts from Simulated gastric fluid fast (SGFfast) to fasted state simulated intestinal fluid, slight turbidity appeared after 30min, and the amount of drug dissolved slightly decreased from 96.91% to 90.59%. However, after the transfer from SGFfast to fed state simulated intestinal fluid, no turbidity or precipitation occurred throughout time of the test (60min). In vivo pharmacokinetic study in human volunteers proved the success of the in vitro models with enhancement of the oral bioavailability (121.20%) compared to the commercial product.

• 出版日期2016-3-23