Parameters that determine dissolution and efficacy of itraconazole and its relevance to recalcitrant dermatophytoses

Abstract

INTRODUCTION: Recalcitrant dermatophytoses is on the rise. Though myriad factors contribute to recalcitrance including terbinafine resistance, itraconazole largely remains sensitive. However, there are increasing instances of patients not responding adequately to itraconazole despite low MICs, probably due to issues plaguing the pelletization process, resulting in suboptimal quality. Data on this topic was searched on pubmed using the search items: itraconazole, MIC, MFC, quality, assay, pharmacokinetics, pharmacodynamics, dermatophytoses, and recalcitrance. Areas covered: A detailed analysis of the manufacturing process of itraconazole with emphasis on pelletization and parameters affecting the dissolution and bioavailability is presented. Important formulation factors including drug-polymer ratio, polymer type, coating thickness, bead size, and number are discussed. Also covered is the rationale of dosimetry of itraconazole in dermatophytoses based on the skin pharmacokinetics and MIC of the organism. Expert opinion: The process of pelletization has multiple components aiming to achieve maximum dissolution of the drug. Variations in the process, pellet quality, number, and polymer determine absorption. Morphometric analysis of pellets is a simple method to quantify quality of the drug. Once the process has been standardized, dosimetry depends on the route of secretion and site of infection, accounting for the variation of doses from 100 mg to 400 mg/day.