Evaluating the effect of kosmotropic inorganic salts in the in vitro dissolution behavior of tablets containing amorphous indomethacin-polyvinylpyrrolidone solid dispersions

Abstract

The present study evaluates the effect of kosmotropic inorganic salts in the disintegration time and the in vitro dissolution behavior of tablets containing polyvinylpyrrolidone (PVP)-based amorphous solid dispersions (ASDs). Specifically, the impact of KH2PO4, KHCO3 and KCl -which have presented kosmotropic effect on hydrophilic polymers at previous studies- on the performance of tablets containing indomethacin (IND)-PVP ASDs was evaluated. Results showed that all the tested potassium salts presented a kosmotropic effect on PVP, while KH2PO4 was identified as the salt with the greatest impact on PVP's cloud point temperature. Contrary to previously published reports, the in vitro dissolution study of the prepared formulations (with and without inorganic salts) revealed that only the addition of KH2PO4 resulted to increased drug in vitro supersaturation rate and extent. As far as the KHCO3 and KCl are concerned, their incorporation into the systems brought about only a marginal increase in the final level of the API's supersaturation. Interestingly, according to the obtained results, as the inorganic salts' concentration increased, the final supersaturation level of IND decreased in all examined cases. Furthermore, in order to evaluate the moisture-effect on the tablets' performance, pharmaco-technical characterization and in vitro dissolution studies of tablets stored at 60% RH/25 °C took place. Results revealed that the presence of the potassium inorganic salts could not control the moisture's impact on the dissolution profiles and the disintegration time of tablets, highlighting that, in contrary to previous findings, the utilization of kosmotropes salts is not to be considered as a universal solution for the improvement of ASD-based tablet's dissolution/supersaturation performance.