Elucidation of alginate-drug miscibility on its crystal growth inhibition effect in supersaturated drug delivery system

摘要

The objective of this study is to investigate the influence of drug-alginate miscibility on maintaining drug supersaturation. Using lovastatin, indomethacin, itraconazole as model drugs, drug-alginate miscibility was estimated by Hansen solubility parameters. The mechanism of drug-alginate miscibility on maintaining drug supersaturation was elucidated by microscopy, molecular mobility (T-2), FTIR and X-ray crystallography. The influence of alginate properties on maintaining drug supersaturation was also examined. It was demonstrated that the capacity of alginate to maintain drug supersaturation was dependent on alginate-drug miscibility. Further mechanistic study revealed that alginate interacts with drugs via hydrogen bonding at different extent based on varied drug-alginate miscibility. Alginate could suppress drug molecular mobility and corresponding crystal growth inhibition. The properties of alginate also play an important role in maintaining drug supersaturation. In conclusion, alginate could be used as a potential crystal growth inhibitor, and the crystal growth inhibition effect depends on drug-alginate miscibility and alginate properties.