Triacetylated andrographolide solid dispersions: Preparation, stability study and in vivo anti-inflammation in mice ulcerative colitis model

摘要

This manuscript reported a preliminary study of triacetylated andrographolide solid dispersion (TA-SD) that investigated the influence of preparation method and carrier materials on the physical stability of prepared SDs, and tested the anti-inflammatory effect of TA-SD. SDs were prepared by hot-melt extrusion (HME) or solvent-evaporation (SE) with fixed drug loading of 10% using Kollidon VA64 (VA64-SD) or Soluplus (So-SD) as carriers. The physical stability of the four prepared SDs was studied after a 7-day exposure to heat (30 degrees C and 60 degrees C) or moisture (75% and 92.5% relative humidity). All SDs samples, except So-SD prepared by HME (So-HME-SD), were found with drug recrystallization after 7-day exposure to 92.5% RH, as illustrated by DSC analysis. All prepared SDs showed reduced dissolution after storage under stressed conditions, and according to their changes in dissolution profiles, it was found that So-SDs were more sensitive to heat while VA64-SDs were more sensitive to moisture, and SDs prepared by HME could inhibited drug recrystallization more effectively. In anti-inflammatory study, TA solid dispersion prepared by HME using VA64 as carrier material showed comparable therapeutic effect against ulcerative colitis with commercial andrographolide drop pills but significant improved activity over crude TA suspension, indicating the necessity of solid dispersion preparation.