Wednesday, April 29April 14, 2020Free AccessAdministration of Lamotrigine Formulation for Oral Suspension (ET-105) Through Gastrostomy Feeding Tubes (1969)Nishant Shah, Danielle Boyce, Prexa Patel, Lixin Gong, Enxian Lu, and Shoufeng LiAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.1969 Letters to the Editor

目的:采用不同工艺制备硫酸氢氯吡格雷固体分散体,并进行生物相关性体外评价,以筛选出理想的生产工艺.方法:将硫酸氢氯吡格雷与Soluplus按1∶1(w/w)混合,分别采用溶剂蒸发法、喷雾干燥法、热熔制粒法和热熔挤出法制备硫酸氢氯吡格雷固体分散体,用X射线衍射法和差示扫描量热法对固体分散体的晶体形态进行检测,运用两单元介质转运法评价各固体分散体在pH 6.8介质中的溶解状态及析出情况.结果:两单元介质转运法是基于生理环境设计的,5 ml/min的泵速对不同工艺制备的硫酸氢氯吡格雷固体分散体有较强的区分力.溶剂蒸发法制备的固体分散体在pH 6.8介质中维持过饱和度的能力低于喷雾干燥法、热熔挤出法和热熔制粒法制备的固体分散体.热熔挤出法制备的固体分散体不稳定,放置后会转变为晶型.热熔制粒法制备的固体分散体中硫酸氢氯吡格雷为晶型,并且工艺不佳.结论:喷雾干燥法工艺稳健,制备的固体分散体稳定,能增加硫酸氢氯吡格雷在pH 6.8介质中的溶解性,保持较高的过饱和度.两单元介质转运法具有生物相关性和区分力,可用于硫酸氢氯吡格雷等弱碱性药物固体分散体的开发.

Supersaturable formulation can generate supersaturation after dissolution, providing kinetic advantage in vivo. However, the supersaturation may precipitate before being absorbed, which makes it difficult to ensure and predict its in vivo performance. The traditional USP method is typically for Quality Control (QC) purpose and cannot be used to predict the formulation in vivo performance. Therefore, there is generally a lack of a predictive biorelevant testing method. In this review, different types of supersaturable formulations are described, including amorphous dispersions, polymorphs, salts/co-crystals, weak base and supersaturable solubilized formulations. Different kinds of in vitro dissolution methods for supersaturable formulations are also reviewed and discussed. Most of the methods take the physiology of gastrointestinal (GI) track into consideration, allowing reasonable prediction of the in vivo performance of supersaturable formulation. However, absorbing drug from GI track into blood stream is a complicate process, which can be affected by different in vivo processes such as transporter and metabolism. These factors cannot be captured by the in vitro testing. Thus, combining in vitro biorelevant dissolution methods with physiology-based pharmacokinetic modeling is a better way for the product development of supersaturable formulation.

Soluble pharmaceutical compositions of amorphous nilotinib or a pharmaceutically acceptable salt thereof were invented using one or more organic acids that function as a solubilizing agent, increasing the bioavailability of nilotinib and supressing the food effect associated with certain compositions of nilotinib. The pharmaceutical compositions are in th form of solid oral dosage forms, including capsules and tablets.