Neat amorphous form and amorphous solid dispersions of apalutamide: A comparative study

Amorphous form and Amorphous solid dispersions (ASDs) of an anticancer drug Apalutamide (APA) with four polymers of different categories namely, PVPK30, HPMCAS, Soluplus and Eudragit L100-55 are investigated. The drug loads were screened based on an in situ drug polymer miscibility study using differential scanning calorimetry. Amorphous form of the API and ASDs prepared for each of the polymers at two different drug loads (20 % w/w and 50 % w/w) were characterized using Powder XRD, DSC and ATR-FTIR. Comparative analysis with regards to in vitro drug release profiles of the ASDs and their physical and chemical stability is provided. The observed trends were evaluated based on the measurements of solubility enhancement ability and nucleation inhibition potential of the polymers. Also, role of surfactant in dissolution media in effecting the drug release is described in relation to the drug load of the ASDs and compared with that of the neat amorphous form. Assessment of dissolution of the polymer alone in the dissolution media provided clear indication of importance of right amphiphilicity of the polymer in achieving maximal drug release. This study reinforces the critical balance of multiple parameters while making the choice of an amorphous phase of the drug for delivering the oral solid dosage form and provides insights into drug-specific requirement of the polymer, balancing product stability and drug release.