In the pharmaceutical industry, dissolution testing of the active ingredient of the final dosage forms is an important tool in the process of drug discovery and analysing the quality of medicinal products. The aim of the thesis was to develop the high-performance dissolution method for a pharmaceutical form with modified release, utilizing an automatic pipettor. Pellet samples with different amount of controlled release coating and an insoluble substance ketoprofen were used. We tested the parameters that could affect the release of ketoprofen: the amount of pellets, agitation rate, temperature and the influence of pre-incubation in acid. We found that the release of the active ingredient from a larger quantity of pellets is reduced, probably because the solubility of ketoprofen limits the dissolution. As a result further analyses were carried out on a smaller amount of pellets (25% of the weight in the capsule or less). It was found that the tested pellets were very robust and resistant to agitation, because the agitation rate did not influence the release of the active ingredient significantly. However, the release of the active ingredient depends strongly on the temperature. As was expected, the release of the active ingredient was higher at higher temperature. Additionally, we observed that the active ingredient of the pellets, which were incubated in 1 M HCl, was not released. To achieve the best correlation to the classical method, various parameters, influencing the release of the active ingredient (amount of pellets: 25, 17,5 and 10 % of capsule filling mass, the temperature of 22, 37 and 50 ° C and the agitation rate of 0, 6 and 8 Hz) were evaluated by design of experiments (DoE). The responses studied were the correlation of the scaled-down dissolution method with the classical method (R2), the slope of the correlation curve (k), and the standard deviation between the methods (Syx). The responses were adjusted to the regression model. The results have revealed that low T (22 °C), no shaking and high amount of pellets (25% capsule filling mass) were parameters that resulted in the best correlation between both dissolution methods for ketoprofen controlled release pellets. At these conditions the value of R2 (0,9707) was the highest and value of SYX (5.35) the lowest. (It has thus been shown that for good correlation it is important to achieve a slow release at low temperature, while a higher amount of pellets reduces variability. These results show that with proper selection of parameters we can achieve a good correlation between the two methods. Since the rate and extent of samples analysed by classical dissolution testing is limited, it is important to develop alternative high-throughput methods for pharmaceutical industry.
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