ABSTRACT
A direct imaging system (EyeconTM) was used as a Process Analytical Technology (PAT) tool to monitor fluid bed coating process. EyeconTM generated real-time onscreen images, particle size and shape information of two identically manufactured laboratory-scale batches. EyeconTM has accuracy of measuring the particle size increase of ±1 µm on particles in the size range of 50-3000 µm. EyeconTM captured data every 2 s during the entire process. The moving average of D90 particle size values recorded by EyeconTM were calculated for every 30 min to calculate the radial coating thickness of coated particles. After the completion of coating process, the radial coating thickness was found to be 11.3 and 9.11 µm, with a standard deviation of ±0.68 and 1.8 µm for Batch 1 and Batch 2, respectively. The coating thickness was also correlated with percent weight build-up by gel permeation chromatography (GPC) and dissolution. GPC indicated weight build-up of 10.6% and 9.27% for Batch 1 and Batch 2, respectively. In conclusion, weight build-up of 10% can also be correlated with 10 ± 2 µm increase in the coating thickness of pellets, indicating the potential applicability of real-time imaging as an endpoint determination tool for fluid bed coating process.
Subject(s)
Drug Compounding/methods , Optical Imaging/methods , Tablets/chemistry , Chromatography, Gel , Drug Compounding/instrumentation , Equipment Design , Excipients/chemistry , Optical Imaging/instrumentation , Particle Size , Pharmaceutical Preparations/chemistryABSTRACT
Current endeavor was aimed towards monitoring percent weight build-up during functional coating process on drug-layered pellets. Near-infrared (NIR) spectroscopy is an emerging process analytical technology (PAT) tool which was employed here within quality by design (QbD) framework. Samples were withdrawn after spraying every 15-Kg cellulosic coating material during Wurster coating process of drug-loaded pellets. NIR spectra of these samples were acquired using cup spinner assembly of Thermoscientific Antaris II, followed by multivariate analysis using partial least squares (PLS) calibration model. PLS model was built by selecting various absorption regions of NIR spectra for Ethyl cellulose, drug and correlating the absorption values with actual percent weight build up determined by HPLC. The spectral regions of 8971.04 to 8250.77 cm-1, 7515.24 to 7108.33 cm-1, and 5257.00 to 5098.87 cm-1 were found to be specific to cellulose, where as the spectral region of 6004.45 to 5844.14 cm-1was found to be specific to drug. The final model gave superb correlation co-efficient value of 0.9994 for calibration and 0.9984 for validation with low root mean square of error (RMSE) values of 0.147 for calibration and 0.371 for validation using 6 factors. The developed correlation between the NIR spectra and cellulose content is useful in precise at-line prediction of functional coat value and can be used for monitoring the Wurster coating process.
