title: Gelucire and Gelucire-PEG400 formulations; tolerability in species used for non-clinical safety testing after oral (gavage) dosing.
abstract: 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 5 days in minipigs, 7 days in rats and up to 39 weeks 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 1 ml kg(-1) once daily for 39 weeks, and 100% Gelucire was tolerated in the rat and the minipig when administered once daily at 5 ml kg(-1) for 5 days. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Department of Regulatory Toxicology & Safety Assessment, H. Lundbeck A/S, Ottiliavej 9, DK, 2500, Valby, Denmark. miel@Lundbeck.com.
authors: Mikael
authors: M
authors: Elander
authors: Pharmaceutical Science & CMC Biologics, H. Lundbeck A/S, Ottiliavej 9, DK, 2500, Valby, Denmark.
authors: Jette B
authors: JB
authors: Boll
authors: Department of Regulatory Toxicology & Safety Assessment, H. Lundbeck A/S, Ottiliavej 9, DK, 2500, Valby, Denmark.
authors: Anne S
authors: AS
authors: Hojman
authors: Department of Regulatory Toxicology & Safety Assessment, H. Lundbeck A/S, Ottiliavej 9, DK, 2500, Valby, Denmark.
authors: Allan D
authors: AD
authors: Rasmussen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature; D018675:Toxicity Tests
chemical_list: D014677:Pharmaceutical Vehicles; C104509:gelucire 44-14; D011092:Polyethylene Glycols
keywords: Gelucire; PEG400; non-clinical; species; tolerability