Ammonio methacrylate copolymers are commercially available as Eudragit RL/RS; they differ in the degree of quaternary ammonium group substitution, which gives them different permeabilities. These closely related polymers can be combined in various ratios to control release rate; consequently, release rate is controlled by the polymer composition and coating thickness. Therefore, predicting drug release from methacrylate copolymers using near infrared spectroscopy (NIRS) can be technically difficult. Thus, the objective of this study is to use NIRS to develop multivariate calibration models to predict tablet coat thickness and release rate for tablets coated with varying polymer ratios. A series of sustained release orbifloxacin formulations were developed with varying polymer ratios. Partial least squares (PLS) models were developed to predict coat thickness; samples from these formulations were pooled and a combined calibration was generated. To assess dissolution, tablets were coated using Eudragit RL and RS with ratios of 0:5, 1:4, 2:3, 3:2, 4:1, and 5:0. The amount released at set time-points was used to build PLS models. For the first time, NIRS has been successfully used to monitor Eudragit polymer coat thickness and drug release from tablets coated with various RL:RS ratios, which demonstrates the potential of NIRS as tool for coating process.