Investigation on drug dissolution and particle characteristics of pellets related to manufacturing process variables of high-shear granulation.

There is a growing interest for multiparticulate solid dosage forms such as pellets, because of their several advantages over tablets during drug therapy. It is essential to investigate the drug dissolution process which can be influenced by the composition and manufacturing process technology, too. This study was performed applying experimental design in order to evaluate the effects of independent process variables during high-shear pelletisation, taking the impeller speed (x1) and granulation binder flow rate (x2) as factors into consideration. Theophylline containing pellet formulation was prepared using a matrix consisted of ethylcellulose, microcrystalline cellulose and lactose. Dissolution profiles were modeled by the Weibull function to evaluate the power of process variables. Both process variables were powerful to influence the particle agglomeration. A linear regression was found between the particle size and the diffuse reflectance values after the Kubelka-Munk transformation. Differences in the diffuse reflectance spectra of pellet samples related to particle size offer a fast instrumental method for the in-process control.