Bilayer tablets are peroral formulations, which consist of one or more drugs formulated together in one or both layers or kept separately in different layers. Each drug may exert its individual release rate, which can be either immediate and/or modified, depending on the selection of excipients. Hydrophilic matrices are the most commonly used drug delivery systems for sustained release and the most frequently used polymer is hypromellose. Drug release from such tablets occurs via diffusion and erosion or combination of them. The rate and extent of drug release strongly depend on polymer selection and its properties such as polymer swelling, gel formation and gel structure. This focus of this paper was observation of drug release from a poorly soluble drug from both immediate release as well as modified release layer, while focusing mainly on modified release layer. The aim of this master’s thesis was to evaluate the influence of poorly soluble drug particle size distribution on drug release from both layers of bilayer tablet. Additionally influence of functionality-related characteristics of hypromellose on drug release from modified layer was evaluated. Dissolution testing was carried out using USP 2 in potassium phosphate buffer pH 6,8 and USP 3 in two-stage test with acid and buffer phase. The later method was found to better differentiate between formulations i.e. its discriminatory power is greater. Dissolution results obtained with USP 2 in potassium phosphate buffer pH 6,8 indicate that viscosity and degree of hydroxypropoxy substituted hypromellose significantly influence drug release. Using a more viscous polymer results in slower dissolution profile, whereas higher content of hydroxypropoxy groups in the polymer cause an increase in dissolution rate. Particle size distribution of hypromellose has no significant influence on drug release using USP 2 method. The use of USP 3 (two-stage test with acid and buffer phase) displayed substantially faster drug release from bilayer tablet samples prepared with different particle size distribution of drug substance in immediate release layer and significantly slower drug release in samples with increased amount of hypromellose. No influence of particle size distribution was observed with use of USP 2 (in potassium phosphate buffer pH 6,8), while the method confirmed slower drug release from samples with increased hypromellose amount. Using both methods in our evaluation we concluded that both hypromellose properties and particle size distribution of model drug substance significantly influence drug release. It was also confirmed that results from method using USP 3 (two stage test with acid and buffer phase) have good correlation with in-vivo results.
|
