Various approaches can be used to design oral prolonged release delivery systems, while the majority of modern technologies are based on polymeric systems. Precisely, diffusion-controlled delivery systems are currently the most widely utilized. In this master thesis, the impact of polyvinylpyrrolidone (PVP) and process parameters of high-shear wet granulation to various physicochemical properties of hydrophilic matrix tablets based on hypromellose (HPMC) was studied. Using design of experiment (DoE) approach, we conducted full 3-factor 2-level experimental design. Two sets of experiments were carried out in order to examine the influences of the following input parameters: amount of PVP in tablet composition, amount of water for wet granulation, mesh screen size and tablet compression force. Multiple linear regression analysis was used to evaluate the influences of listed factors to physicochemical properties of tablets as well as drug dissolution. Based on model results, the amount of water used for granulation and tablet compression force are the factors with the considerable impact on the quality of final product (rate of dissolution, tensile strength, prolonged friability, porosity). Varying these two factors, we managed to obtain tablets with appropriate prolonged release despite the low amount of HPMC in tablet composition. Increment of the amount of water for granulation, reduced the time needed for matrix erosion, and consequently decreased the rate of drug release, PVP in tablet composition decreased the rate of drug release and reduced friability. Larger granules impact higher friability of tablets and increase the rate of drug release. Elevation of the compression force increases the tablet tensile strength, decreases friability and tablet porosity, and consequently prolongs the matrix erosion.
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