Evaluation of Different Methods for Dissolution Profile Similarity Comparison of Montelukast Tablets in Türkiye

Abstract

This study aimed to evaluate the highly variable in vitro dissolution profiles of generics and innovator montelukast products in the Turkish drug market by comparing model-dependent and model-independent analysis methods. Seven generic montelukast sodium products were tested, labeled G1-G7, and compared with the innovator. Dissolution tests were carried out with United States Pharmacopeia (USP) apparatus 2 (paddle) in 900 mL of distilled water containing 0.5% sodium dodecyl sulfate (SDS), fasted state simulated intestinal fluid (FaSSIF), or fed state simulated intestinal fluid (FeSSIF). The most accepted and used model for dissolution profile comparison of regulations in the world is the modelindependent similarity factor (f 2 ); however, in this study, the bootstrap f 2 confidence interval method was also used due to highly variable dissolution data. The values of f 2 , f ̂2,exp , and f ̂2,bc were calculated with DDSolver, Bootf2BCA, and PhEq_bootstrap software. DDSolver was also used for model-dependent calculations. Two generic products showed similarity with the innovator (f 2 > 50) in biorelevant media (G4 in FeSSIF and G7 in FaSSIF); however, satisfactory results were not obtained in 0.5% SDS. The observed differences may be due to the dissolution method or nature of montelukast sodium (i.e., pH-dependent, poorly water-soluble, first-pass metabolism-exposed drug).