Polymer selection for amorphous solid dispersion of a new drug candidate by investigation of drug polymer molecular interactions

The antitumor drug candidate X-05 is being developed as an innovative anti-lung cancer drug candidate due to its excellent antitumour activity. A Caco-2 cell permeability study and solubility study confirmed that X-05 belonged to BCS class II or IV compounds. Therefore, the main challenge is to develop appropriate preparations for preclinical studies and further clinical phase research. By evaluating the preliminary results of kinetic solubility in biorelevant media and the structural analysis of X-05 and polymers, three polymers PVP K30, PVP VA 64 and HPMCAS, which may have intermolecular interactions with X-05, were chosen to select the optimal carrier for X-05 to prepare amorphous solid dispersions (ASDs). ASD X-05-PVP VA 64 was selected as the optimal polymer by evaluating its kinetic solubility in biorelevant media and solid stability. The physical and chemical properties of ASD X-05-PVP VA 64 remain stable when the drug loading is as high as 50%. The drug-polymer interactions of ASD X-05-PVP VA 64 were studied by ultraviolet spectrophotometry, nuclear magnetic resonance spectrometry, infrared and Raman spectrophotometry, and the results indicated that the intermolecular hydrogen bond interaction between the drug and polymer was the foundation of the solubilization and stabilization of X-05 in PVP VA 64.