Characterizing and Exploring the Differences in Dissolution and Stability Between Crystalline Solid Dispersion and Amorphous Solid Dispersion.

Abstract

Solid dispersion is one of the most effective ways to improve the dissolution of insoluble drugs. When the carrier can highly disperse the drug, it will increase the wettability of the drug and reduce the surface tension, thus improving the solubility, dissolution, and bioavailability. However, amorphous solid dispersions usually have low drug loading and poor stability. Therefore, the goal of this work is to study the increased dissolution and high stability of high drug-loading crystalline solid dispersion (CSD), and the difference in dissolution and stability of high-loading and low-loading amorphous solid dispersion (ASD). A CSD of nimodipine with a drug loading of 90% was prepared by wet milling, with hydroxypropyl cellulose (model: HPC-SL) and sodium dodecyl sulfate as stabilizers and spray drying. At the same time, the gradient drug-loaded ASD was prepared by hot melt extrusion with HPC-SL as the carrier. Each preparation was characterized by DSC, PXRD, FT-IR, SEM, and in vitro dissolution testing. The results indicated that the drug in CSD existed in a crystalline state. The amorphous drug molecules in the low drug-loading ASD were uniformly dispersed in the carrier, while the drug state in the high drug-loading ASD was aggregates of the amorphous drug. At the end of the dissolution assay, the 90% drug-loading CSD increased cumulative dissolution to 60%, and the 10% drug-loading ASD achieved a cumulative dissolution rate of 90%.