S. Hassannejad Tabasi1 , R. M. Fahmy2 , D. M. Bensley2 , W. G. Marnane2 , S. W. Hoag1 , 1School of Pharmacy, University of Maryland, Baltimore, MD 21201, 2Office of New Animal Drug Evaluation, FDA, Rockville, MD 20855
Background: NIR spectroscopy is an important toolbox for quality-by-design, which can be utilized to assess physical and chemical properties of similar materials. This study examines the monitoring of sustained release coating process.
Methods: Sustained release formulations for orbifloxacin were developed using varying ratios of Eudragit RL and RS 30-D. Tablets were coated in pan coater to a target thickness of 70-80ìm, and the coat thickness was monitored using NIR spectroscopy. A total of 939 tablets from 10 batches were used to build best-fit calibrations to predict thickness and release profile. Different PLS calibrations were developed and their statistical parameters such as standard error of calibration (SEC), cross validation (SECV), prediction (SEP) and coefficient of correlation were compared.
Results: Three PLS models for coating thickness of Eudragit RL, RL:RS (2:3) and RL:RS (1:4) had SECs of 3.19, 2.97, 2.84µm and SEPs of 2.92, 2.58, 3.03µm, respectively. The combined calibration yielded a SEC and SEP of 2.91 and 3.05µm. To assess the release, seven different ratios of RL/RS were made and the release after 2hrs in acetate buffer (0.1 M, pH 3.95 ±0.05) was used to build a six factor PLS regression. The PLS regression provided SEC, SEP and correlation coefficient of 2.66%, 2.47%, and 0.9948, respectively.
Conclusion: NIR spectroscopy combined with multivariate calibration is a powerful tool for predicting drug release from blends of Eudragit. In addition, due to the similarities in the structure of Eudragit RL/RS, one properly developed model would be able to predict coat thickness from the blend with satisfactory SEP.