Dissolution Methods for Microsphere and Implant Drug Products

Dissolution testing is recommended as part of the demonstration of bioequivalence between test and reference products in the approval of most generic drugs. Drug release measurements are useful for evaluating the effect of manufacturing differences and to assess performance characteristics of a sustained release dosage form. Generally, a generic drug product intended for parenteral use contains the same inactive ingredients (“Q1”) and in the same concentration (“Q2”) as the Reference Listed Drug (RLD). However, there may be differences in manufacturing of the generic and RLD products, which may affect bioavailability. Dissolution testing can be used as one of several standard methods to evaluate physicochemical differences of the drug product caused by manufacturing differences. The purpose of this study is to investigate dissolution methods for a parenteral sustained release drug product. The results from this study will help the FDA in developing recommendations to determine bioequivalence of generic parenteral sustained release drug products.Objectives:(1) To formulate Q1/Q2 sustained release products (either microspheres or implants) under different manufacturing conditions(2) To conduct dissolution studies with the prepared sustained release formulations using various in vitro release methods(3) To identify a dissolution method that can discriminate different sustained release formulations Detailed Description:Additional details regarding the study objectives listed above:(1) The sustained release formulation chosen to serve as the reference product for this study can either be a marketed product or an investigational formulation. Formulations which are Q1/Q2 to this reference product should be developed under different manufacturing conditions. Physicochemical characterization should be performed on these test formulations to determine key attributes that may affect bioavailability.(2) Before initiating the dissolution studies, an analysis of current dissolution methods used for sustained release products (either microspheres or implants, depending on the dosage form chosen) should be conducted. A report of this analysis should include the advantages and disadvantages for each method and an assessment on the capability of detecting manufacturing differences, predicting in vivo performance, and method robustness. Test formulations which have the largest differences in physicochemical properties (and which are expected to affect bioavailability) are chosen for testing in the dissolution study. Dissolution methods should be developed with considerations in drug substance and drug product properties and the physiological release environment.(3) An analysis of the dissolution methods used in the study should include the advantages and disadvantages for each method and an assessment on the capability of detecting manufacturing differences, predicting in vivo performance, and method robustness.