engleski

By mechanochemical activation to a drug with an improved solubility and release rate

The low aqueous solubility of lurasidone hydrochloride, a drug used for the treatment of mental disorders, results in its poor gastrointestinal absorption, low bioavailability, and overall inadequate pharmacological effect. A promising approach to improve its solubility is the mechanochemical preparation of an amorphous solid dispersion with different polymers. In this study, solid dispersions of hydrophobic lurasidone hydrochloride in hydrophilic polymeric carriers, polyvinylpyrrolidone and hydroxypropyl methylcellulose, were made in different drug-to- polymer ratios by mechanochemical activation in a planetary ball mill. The solid dispersions were characterized by XRPD, FTIR and DSC analyses. Tablets with a diameter of 8 mm were successfully prepared using solid dispersions of the drug, in- situ fluidized bed melt granulation and traditional tableting. The tablets were analyzed for mass uniformity, disintegration and drug content. In vitro release profiles in the presence of McIlvaine buffer (pH = 3.8) showed a significant improvement in the solubility and release rate of lurasidone hydrochloride from tablets containing mechanochemically prepared solid dispersions compared with those containing the crystalline and untreated drug or its physical mixture with the polymer. Tablets containing the polymeric carrier polyvinylpyrrolidone exhibited faster drug release than tablets containing hydroxypropyl methylcellulose, which is used in extended-release oral dosage forms to provide a continuous supply of the drug over a longer period. The results presented confirm that lurasidone hydrochloride can be activated mechanochemically in terms of improving its in vitro dissolution and release properties.

lurasidone hydrochloride ; drug solubility improvement ; solid dispersion ; mechanochemical activation ; tablet ; drug release

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