Biopharmaceutic Considerations in Designing and Evaluating Novel Drug Delivery Systems
Jerome P. Skelly, William H. Barr · Clinical Research Practices and Drug Regulatory Affairs · 1985
The article considers the various categories of controlled release preparations including oral, intramuscular, cutaneous/percutaneous and targeted. It briefly outlines the requirements for demonstration of safety and efficacy, differentiating these by a drug product marketing status, e.g., DESI, post 62 drugs, the conditional status of transdermal nitrates, etc. It delineates the bioavailability requirements and the types of studies which would be normally required for approval.Both single dose and steady state bioavailability study data as well as in vitro dissolution data are normally required for approval. The conditions for assuring steady state conditions are given, and the type of evaluation employed by the Agency is explained. For instance, generally controlled release dosage forms are best described by the flip flop pharmacokinetic model where a Wagner Nelson analysis is employed to determine the amount of first order/zero order input. The condition for approval of additional strength of a formulation is given as well as the meaningfulness of in vitro dissolution data. Blood level fluctuations, in terms of Cmax-Cmin, are determined. Where a therapeutic window exists, occupancy time is determined.