Application of process analytical technology in the preparation of taste-masked azithromycin dry powder

Abstract

One of the most widespread Process Analytical Technology (PAT) tool is Near-Infrared (NIR) spectroscopy, which is a fast and non-invasive analytical technique with no sample preparation necessary. Azithromycin, Eudragit® E PO and their physical mixtures were initially characterized by microscopic, spectroscopic, thermal and powder X-ray analyses. PAT using NIRs was developed to qualitatively monitor the homogeneity end-point in taste masking of azithromycin powder during blending in Erweka® AR400 Universal Lab mixer. A quantitative model in PMS® MG15T mixer was also constructed. For these purposes, fiber optic probe NIRs diode array spectrometer with fast data acquisition was selected. The results show well-defined clusters differentiating the homogeneous and non-homogeneous states. The homogeneity state of the taste-masked blending process was detected by Principal Component Analysis (PCA). The results were evaluated by chemometric analysis which results in the optimum solid ratios of Eudragit® E PO to azithromycin and blending time of 0.4:1 and 20-30 minutes, respectively. Partial Least Square (PLS) regression models based on the NIRs data and HPLC data were calibrated and validated. From this study, NIR spectroscopy is proven to be a suitable PAT tool for the real-time end-point monitoring for blend homogeneity and taste masking process. Additionally, this study provides useful information to improve and verify the quality of pharmaceutical dosage forms such as dry powder for suspensions.