Development composite polymer matrix tablets with a preset time of isosorbide dinitrate release by the method of mathematical modeling

Abstract

The kinetics of release of isosorbide dinitrate from coated and uncoated granules with a diameter of 0.5–0.8 mm and 0.8–1.25 mm used for the preparation of matrix tablets was studied. A statistical analysis of the results is made. For the same time value and different pH values, the mean values of release and empirical values of the Shapiro – Wilk criterion were calculated. For a series of series at the same time and different pH, the empirical values of the Cochren test and the non-parametric Cruskell – Wallis test are calculated considering the repeating groups and the Iman – Davenport correction for the number of elements in the sample. A low pH effect on release kinetics has been established. When modeling the release of pellet-based tablets, the characteristics of the normal distribution for each of the granule types and each time value are used. The amount of each type of granules that make up the tablet core is calculated to achieve the desired release profile in Excel using the Search Solver add-in. For the mean values of release for the granules of three types by the least square’s method, we obtained the mass values of the total content of isosorbide dinitrate. For experimental verification of the model, a batch of matrix tablets was prepared using coated and uncoated granules with a diameter of 0.5–0.8 mm. A study of the kinetics of release of isosorbide dinitrate from tablets at pH 1.2; 4.5; 6.8. A statistical analysis of the obtained data and a comparison of the results with calculations by the model were carried out. It has been established that the approach used makes it possible to describe the release of isosorbide dinitrate from tablets with an acceptable accuracy. The accuracy criterion is established - the experimental profile of release of the developed composition falls within the boundaries between the maximum and minimum desired profile. As a result of the research, a composite drug of prolonged action Dikor Long based on isosorbide dinitrate has been developed. The drug has passed state tests, its industrial production has been adjusted in Research and Production Company "Microkhim".