A canine biorelevant dissolution method for predicting in vivo performance of orally administered sustained release matrix tablets

摘要: Preclinical species are a crucial component of drug development, but critical differences in physiology and anatomy need to be taken into account when attempting extrapolate humans or between species. The same is true trying develop oral formulations for preclinical species, especially unconventional formulations, such as sustained release tablets. During the evaluation specialized dosage forms, dissolution can vitro tool used rank-order ultimately choose desired rate. Here, development canine biorelevant method prediction vivo performance matrix tablets beagle dogs described. accounts gastrointestinal fluid composition, gastric emptying forces, residence time. most parameters were found paddle speed simulate forces well time spent simulated fluid. resulting conditions further explored through silico models hydrodynamic applied form. Two case studies reported showing that was able obtain excellent vitro-in relationships (slopes ranging from 1.08-1.01) which significantly (p < 0.01-0.05) improved compared human predict ∼1.5-1.75). quality method's predictive ability allows it help drive intended studies.