Some medicinal particles are poorly soluble in highly acidic solutions, particularly those subjected to various production processes. Therefore, the present research investigated the kinetics and mechanisms of the drug release rate of newly formulated solid pills in a low pH medium. Three pills were prepared: one from a non-moisturized powder mixture (PILD) and the other two, PILC and PILM, from the dried powder mixtures, which were dried using hot-air heating and microwave radiation, respectively. These pills were subjected to drug release tests, and the outcomes were considered in the kinetics investigation using various models. Zero-order, Hixson–Crowell, First-order, Higuchi, Hopfenberg, Korsmeyer-Peppas, Logistic, and Peppas-Sahlin were the kinetic models used to inspect the release rate mechanism of these tablets. It was found that the Peppas-Sahlin and zero-order were the most reliable models to represent the drug release profile of all prepared pills with very high accuracy, estimated by R^2>0.99. The Hixon and first-order models were the weakest to characterize this work outcome. This work also applied these models to describe the controlling mechanism of the drug release for each prepared pill. It is detected that the non-Fickian diffusion and polymer chain relaxation control the PILC’s release behavior. However, case II transport and super case II transport with erosions is the dominant mechanism for PILD and PILM pills, respectively. Additionally, new semi-empirical models were modified to describe the kinetics of the solid release of those tablets with greater accuracy.
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