Gelucire and Gelucire-PEG400 formulations; tolerability in species used for non-clinical safety testing after oral (gavage) dosing

摘要

The selection of a vehicle for oral formulations of compounds to be used in non-clinical safety studies is a challenge for poorly soluble compounds. Typically a compromise between solubility and tolerability has to be reached. Vehicle tolerability data are not readily available for a number of vehicles, and a series of oral tolerability studies were, therefore, conducted with Gelucire and Gelucire:PEG400 formulations in rats, dogs and minipigs in order to determine tolerable daily dose volumes in these species. Gelucire and Gelucire:PEG400 formulations were assessed in studies for up to 5days in minipigs, 7days in rats and up to 39weeks in dogs. Gastrointestinal side effects in terms of soft and/or liquid faeces were noted in all species, but the sensitivity to these effects differed between species with the dog being the most sensitive. It was concluded that Gelucire:PEG400 (90:10) was tolerated in Beagle dogs when administered at 1mlkg(-1) once daily for 39weeks, and 100% Gelucire was tolerated in the rat and the minipig when administered once daily at 5mlkg(-1) for 5days. Copyright (c) 2016 John Wiley & Sons, Ltd.