Integration of Near-Infrared Spectroscopy and Mechanistic Modeling for Predicting Film-Coating and Dissolution of Modified Release Tablets

This study demonstrates the feasibility of predicting polymeric film coating and dissolution of theophylline (active pharmateutical ingredients, API) tablets based on integration of multivariate data analysis of near-infrared (NIR) spectra and first-principal modeling. Tablets of various API strengths were manufactured and were spray-coated in a fluid bed using a mixture of ethyl cellulose and hydroxypropyl methylcellulose. Tablets were subjected in NIR spectroscopy and in vitro USP dissolution testing. The characteristic peaks of coating materials were identified via Norris Gap second derivative preprocessing of the NIR spectra of coated tablets. Principal component analysis revealed a linear relationship between PC1 score and tablet coating level. Principal component regression and partial least squares calibration models were developed to correlate the NIR spectra with the dissolution data within the time window of 10–120 min. A linear relationship between tablet initial dissolution rate and tablet coa...