Process Design and Optimization for the Continuous Manufacturing of Nevirapine, an Active Pharmaceutical Ingredient for HIV Treatment

Abstract

The development of efficient and cost-effective manufacturing routes toward HIV active pharmaceutical ingredients (APIs) is essential to ensure their global and affordable access. Continuous pharmaceutical manufacturing (CPM) is a new production paradigm for the pharmaceutical industry whose potential for enhanced efficiency and economic viability over currently implemented batch protocols offers promise for improving HIV API production. Nevirapine is a widely prescribed HIV API whose continuous flow synthesis was recently demonstrated. This paper presents the technoeconomic optimization of nevirapine CPM, including the continuous flow synthesis and a conceptual continuous crystallization. Arrhenius law parameter estimation from published reaction kinetic data allows explicit modeling of the temperature dependence of the reaction performance, and an experimentally validated aqueous API solubility computation method is used to model crystallization processes. A nonlinear optimization problem for cost minim...