Extrusion and spheronization is a widely used method of producing pellets. It gives us compact pellets with narrow particle size distribution and low friability, which are their important characteristics for film coating. Due to the complexity of the process, we can use advanced optimization methods such as the design of experiments, which allows us to quantify the effect of multiple process parameters and predict the characteristics of end product at chosen parameters. Pellets are usually coated in a fluid bed using the bottom spray technique. Relying on the consumption of coating dispersion to determine the process end point could cause high variability of film coating thickness. To achieve higher repeatability, real time process monitoring techniques are being increasingly applied.
Using the design of experiments we have determined optimal values of following process parameters of radial extrusion: water content in granulated mass, size of extrusion screen and the extrusion speed. The goal was to produce spherical extrudates with narrow particle size distribution and low friability. Optimal process parameters according to DoE model were larger extrusion screen (0,8 x 0,7 mm), the highest water content in granulated mass (110% of dry matter mass) and the lowest extrusion speed (15 rpm). Using chosen process parameters we made a larger quantity of extrudates, part of which was later spheronized and the other part was milled using HammerWitt hammer mill.
During film coating, we have measured the near infrared (NIR) spectra of coated pellet samples taken at known applied coating suspension. To further validate the results we added dye tartrazine to coating suspension and later determined its content using ultraviolet and visible (UV/VIS) spectroscopy from which we calculated the quantity of applied coating suspension. Using gathered data we've created partial least squares regression (PLS) models for the prediction of applied coating quantity by at-line NIR measurements of coated pellets. Models were tested in additional coating experiments with the goal to determine the end point using only spectral data. The end result of film coating was compared to earlier experiments in respect to the quantity of applied coating suspension and coating thickness measured by scanning electron microscope (SEM). The predicted quantity of applied coating suspension for spheronized pellets was higher (110 %) than the target value. In the case of milled pellets, we've managed to accurately predict coating quantity (100,3 %) and stop the coating process close to the target value.
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