Relationship Between Dissolution Rate in Vitro and Absorption Rate in Vivo of Ketamine Prolonged-Release Tablets

BACKGROUND AND OBJECTIVES: Understanding the processes that determine the time course of drug absorption rates is of great interest. This study aims to answer the questions: (1) How well can the in vitro dissolution rate predict the in vivo input function (absorption rate) of a prolonged-release ketamine dosage form (PR-ketamine)? (2) Is the information obtained from the in vitro dissolution rate profile useful in estimating bioavailability? METHODS: In vivo plasma concentration data were obtained from 15 healthy volunteers after intravenous and oral dosing of 20 mg PR-ketamine tablets. Both the dissolution and input rates were modeled by a sum of two inverse Gaussian functions. RESULTS: The absorption process was dissolution-limited but the mean input time exceeded the mean dissolution time. When the delayed dissolution rate was used to fit the oral data, the estimated bioavailability was nearly identical to that obtained with the full model. The in vitro dissolution rate profile could be used to develop a one-point sampling strategy for predicting bioavailability. According to their fractional rate profiles, dissolution and input rates belong to different classes of functions. CONCLUSION: A comparison of the time course of the absorption rate with that of the dissolution rate can reveal more details of the absorption process.