A Statistical and Analytical Approach for Discriminating Formulation Variability in Nepafenac Ophthalmic Suspension Via In-vitro Dissolution

Abstract

Dissolution plays an important role as an in-vitro release test for any pharmaceutical product life cycle. Discriminatory dissolution profiles are highly desirable for differentiation between products having differences in their pharmaceutical attributes (formulation and/or manufacturing processes differences) that may reflect corresponding differences in vivo. Substantial changes in CPPs and CMAs for any drug product would not be detected if a dissolution method will not be discriminatory and batches will pass the test which are not bioequivalent. This study demonstrates discriminatory power of dissolution method for Nepafenac ophthalmic suspension, a BCS Class 4 drug. Excipient which were identified critical for the product characteristics, were altered and eight different formulations were developed for evaluation. Due to change of excipients quantities characteristics of formulations changes like, particle size of drug substances, osmolality, pH, and viscosity.  A USP Apparatus IV-based dissolution method using simulated tear fluid was employed for generation of dissolution profiles. A developed high-performance liquid chromatographic method was used to assess the drug release. The dissolution profiles of all eight samples were compared using the similarity factor (f2) and statistical analysis i.e. Paired T-Test and One-way Anova with the help of Minitab software. A clear change in dissolution profiles was observed to distinguish change in excipient concentration in the formulation which was further statistically proved that all the formulations are not similar. Hence it can be concluded that developed method has significant discrimination capability. Since no monograph is available for the Nepafenac ophthalmic suspension formulation, the suggested dissolution technique can be used for quality control and comparing the dissolution profiles of various R&D and commercial formulations.