Concept of Mapping

Abstract

Mapping is a process of relating critical manufacturing variables (CMVs) to the in vitro dissolution profile and to in vivo bioavailability. The CMVs include formulation, process and equipment variables, and materials and method variables commonly employed in the manufacturing process that can significantly affect the in vitro dissolution profile of the product. The goal of mapping is to develop product specifications that will assure bioequivalence of future batches prepared within the limits of acceptable dissolution specifications. The mapping process includes: 1. Preparation of two or more dosage formulations differing in the levels of selected CMVs, and studying their in vitro dissolution characteristics, 2. Testing the formulations with fastest and slowest dissolution characteristics along with the standard or to be marketed dosage form in a small group (n = not less than 12) of human subjects, and 3. Determining the in vitro-in vivo relationship. The formulations with extreme dissolution characteristics may include “side batches” with CMV levels at the limit preestablished or desired formulation specifications. If these formulations are found to be bioequivalent to the reference dosage form, it provides an added assurance that future batches with dissolution characteristics between these ranges will be equivalent. This approach may be viewed as verifying the limits of dissolution specifications.