Tabletting Solid Dispersions of Bicalutamide Prepared Using Ball-milling or Supercritical Carbon Dioxide: The Interrelationship between Phase Transition and In-vitro Dissolution

The studies were aimed at formulating tablets containing bicalutamide-PVP K-29/32 solid dispersions and accessing the interrelationships between the properties of obtained binary systems in the form of powder and compacts. The effect of the compression of the solid dispersions obtained by either milling or using the supercritical fluid method on the dissolution and phase transition of the drug was investigated. Mechanical stress induced the amorphization of the drug, while the treatment with supercritical carbon dioxide did not cause any phase transition as confirmed by X-ray diffractometry. Co-processing of the drug substance with the carrier resulted in even a 10-fold improvement of the bicalutamide dissolution from the solid dispersions. The release of the drug from tablets was lower than from the corresponding powder system. Continue on tableting solid dispersions of Biculatamide here

Conclusions
The study has examined the effect of phase transition on bicalutamide dissolution, with particular emphasis put on the changes induced by the compression. The obtained results reveal that both applied processes, i.e. milling and supercritical carbon dioxide technology, were appropriate to obtain solid dispersions with poorly water-soluble BCL as a model drug. The treatment of BCL and the carrier by scCO2 resulted in dissolution improvement. However, it did not lead to the phase transition of the active substance. In contrast, the milling process led to drug amorphization, which was related to an almost 10-fold enhancement in drug dissolution. The compression was found to cause the amorphization of bicalutamide, which confirmed the high sensitivity of bicalutamide towards mechanical activation. However, the lack of PVP K-29/32 resulted in BCL recrystallization as confirmed by the characteristic Braggs peaks superimposed on the amorphous halo of the compressed drug substance. On the other hand, the pressure applied to the amorphous drug did not affect the physical stability of disordered bicalutamide obtained in milling. The release of bicalutamide from tablets was lower than from solid dispersions in powder form. It was attributed to the binding properties of the carrier, which were the most noticeable during the disintegration time of tablets. Interestingly, the results of stability studies revealed that storage conditions affected the tablets’ properties and dissolution profiles. However, it did not influence the physical state of BCL, which remained amorphous. Continue on tableting solid dispersions of Biculatamide here

Keywords: bicalutamide, planetary ball milling, supercritical fluid, solid dispersion, tabletting, polyvinylpyrrolidone K-29/32, Sodium lauryl sulfate, Carbon dioxide, Cellulose microcrystalline, sodium starch glycolate, magnesium stearate