Multivariate Data Analysis as a Semi-quantitative Tool for Interpretive Evaluation of Comparability or Equivalence of Aerodynamic Particle Size Distribution Profiles

摘要

The purpose of this article is to investigate the performance of multivariate data analysis, especially orthogonal partial least square (OPLS) analysis, as a semi-quantitative tool to evaluate the comparability or equivalence of aerodynamic particle size distribution (APSD) profiles of orally inhaled and nasal drug products (OINDP). Monte Carlo simulation was employed to reconstitute APSD profiles based on 55 realistic scenarios proposed by the Product Quality Research Institute (PQRI) working group. OPLS analyses with different data pretreatment methods were performed on each of the reconstituted profiles. Compared to unit-variance scaling, equivalence determined based on OPLS analysis with Pareto scaling was shown to be more consistent with the working group assessment. Chi-square statistics was employed to compare the performance of OPLS analysis (Pareto scaling) with that of the combination test (i.e., chi-square ratio statistics and population bioequivalence test for impactor-sized mass) in terms of achieving greater consistency with the working group evaluation. A p value of 0.036 suggested that OPLS analysis with Pareto scaling may be more predictive than the combination test with respect to consistency. Furthermore, OPLS analysis may also be employed to analyze part of the APSD profiles that contribute to the calculation of the mass median aerodynamic diameter. Our results show that OPLS analysis performed on partial deposition sites do not interfere with the performance on all deposition sites.