(442ab) Amorphous Nanopharmaceuticals Prepared By Highly Sustainable Electrostatically-Driven Drug-Polysaccharide Complexation

Amorphous nanopharmaceuticals have recently emerged as a promising bioavailability enhancement strategy of poorly-soluble drugs attributed to the high supersaturation solubility generated by the amorphous state and fast dissolution afforded by the nanoparticles. The present work developed a highly sustainable process (in terms of the mass and energy requirement) of preparing amorphous nanopharmaceuticals via drug-polysaccharide electrostatic complexation. The complexation method was performed under ambient condition involving only mixing of the drug and polysaccharide solution at high production yields. No organic solvent was used denoting its highly sustainable feature. A wide range of drugs ranging from antibiotic to anticancer drugs and polysaccharides (e.g. dextran, chitosan, carrageenan) were employed in the study. The amorphous drug-polysaccharide nanoparticle complex (or nanoplex in short) was evaluated in terms of their supersaturation generation capability, payload, in vitro release, and long-term storage stability. The results show that the amorphous nanoplex were superior to the amorphous nanopharmaceuticals prepared by the conventional methods, such as antisolvent and pH-shift precipitation.  The roles of polysaccharides in the preparation as well as in the resultant characteristics were elucidated. The ease of preparation and highly efficient preparation of the drug-polysaccharide complexation make it an ideal process to be implemented for large-scale preparation of amorphous nanopharmaceuticals.