EXPERIMENTAL STUDIES ON FORMULATION OF MODIFIED-RELEASE AMIODARONE TABLETS
Drug formulations and their technological processes must ensure quality and reproducibility in the conditions of the information transfer between research institutions and industry for the preparation of large amounts of pharmaceutical product. Aim: Analysis of the influence of formulation factors on flow parameters of the powder mixture in order to obtain amiodarone tablets. Material and methods: Data fitting and calculation of statistical indicators for the validation of the experimental plan. The study was carried out using the MODDE 10.1 optimization software. The quantitative variables were amiodarone, amiodarone complex with hydroxypropyl-β-cyclodextrin, Kollidon® SR, Chitosan, Aerosil®, magnesium stearate, and Avicel®, while the qualitative variables were the following flow and compressibility parameters of the mixtures subjected to compression: flow time, coefficient of friction, angle of rest, Hausner index and Carr index. The matrix for optimizing the formulation based on the presented parameters was based on a D-optimal experimental design. Results and Discussion: The results of the study on the influence of formulation factors on flow time confirmed that Kollidon® SR concentration levels decrease the flow time, also confirmed for Chitosan but on a smaller scale. Of the formulation factors, Avicel® and Kollidon® SR variables had the greatest influence on the friction coefficient, increasing the concentration of these parameters generating a decrease in the friction coefficient. Conclusions: The use of experimental designs in the formulation of amiodarone tablets and the formulation analysis based on flow and compressibility parameters allows establishing a hierarchy based on the importance of qualitative variables, influenced by quantitative variables, to identify the optimal formulation and technology for the preparation of tablets.
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