Amino acids as co-amorphous excipients for tackling the poor aqueous solubility of valsartan

Abstract

Co-amorphization has recently been shown to be a promising approach for stabilizing amorphous drugs and improving the dissolution rate of poorly water-soluble drugs. In this study, three basic amino acids were chosen as small molecular weight excipients to interact with the drug to form co-amorphous combinations. The co-amorphous combinations of valsartan (VAL) with l-histidine, l-arginine, and l-lysine were prepared by vibrational ball milling. Solid-state characterization with X-ray powder diffraction and differential scanning calorimetry (DSC) revealed that all of the co-amorphous mixtures were homogeneous. The molecular interactions of the co-amorphous mixtures were investigated through the glass transition temperature (T_g) in the DSC measurements and Fourier transform infrared spectroscopy. The drug remained chemically stable during the milling process, and the co-amorphous formulations were generally physically stable over at least 3 months at 40 °C under dry conditions. The dissolution rate of all of the co-amorphous mixtures was significantly increased over that of the amorphous VAL alone. The results of this study demonstrated the potential of amino acids as small molecular weight excipients in co-amorphous formulations to improve the drug solubility and dissolution rate.

Keywords:

• Amino acid
• co-amorphous
• intrinsic dissolution rate
• small molecular excipients
• solubility
• valsartan

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We thank the National Natural Science Foundation of China (Grants 81273479 and 81402898), CAS Key Technology Talent Program, and Youth Innovation Promotion Association CAS for funding.