Amorphous solid dispersion formulation of pimobendan for bioavailability enhancement: A comprehensive study on miscibility, interactions, and in vitro dissolution behavior
Beibei Qu, Hengqian Wu, Zhuang Ding, Rupeng Bu, Heng Zhang, Jun Han, Mingzhong Li, Zhengping Wang
Abstract
Amorphous solid dispersions (ASDs) of poorly soluble pimobendan (PIMO) in cellulose matrices, including hydroxypropyl methylcellulose acetate succinate (HPMCAS-HG, HPMCAS-MG, HPMCAS-LG), polyvinylpyrrolidone-vinyl acetate (PVPVA64), and polyvinylpyrrolidone (PVPK30), were investigated, aiming to identify the optimal polymer to enhance its solubility and stability of the drug product. The results indicated that the miscibility between PIMO and the selected polymers can be predicted by Hansen solubility parameters and Flory-Huggins interaction parameters, with the ranking order of PVPVA64 > PVPK30 > HPMCAS. Fourier transform infrared (FTIR) spectroscopy analysis revealed significant interactions between PIMO and these polymers. Recrystallization inhibition and dissolution performance were ranked as HPMCAS-HG > HPMCAS-MG > HPMCAS-LG > PVPK30 > PVPVA64. Additionally, the results also indicated that HPMCAS-HG had superior stability compared to PVPVA64 and PVPK30 under elevated humidity, as confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analysis. These findings provide a theoretical basis for selection of the optimal polymer for design of PIMO ASDs. • PIMO-polymer miscibility was predicted by HSPs and F-H interaction parameter. • FTIR showed molecular interactions between PIMO and polymers. • HPMCAS-HG outperformed in PIMO recrystallization inhibition and dissolution. • PIMO-HPMCAS-HG ASD showed superior stability in humidity.