Studies On Solvency Enhancement Of Hesperetin And Andrographolide

There are a lot of poorly water-soluble drugs in clinic. Those drugs are slowly absorbed, which lead to low bioavailability and effect their clinical application. In this paper, the solubility of poorly water-soluble drugs which was dispersed in the polymer carrier or inclused byβ-cyclodextrin (β-CD) and its two derivatives hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was studied.The following contents were studied:(1) Ternary solid dispersions consisting of hesperetin, PVPk30 and Polysorbate 80 were prepared in various weight ratios by solvent-evaporation method. Solid dispersions of hesperetin andin PVPk30 in corresponding weight ratios were also prepared for comparison. Dissolution test was performed to investigate the pharmaceutical performance of solid dispersions.The fourier transformation-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffactionary (XRD) were used to identify the status of hesperetin in the ternary solid dispersions.(2) The phase solubility profiles of andrographolide withβ-CD, HP-β-CD and SBE-β-CD were investigated to determine the inclusion types and calculate the stability constants. It was found that the inclusion type of andrographolide withβ-CD was BS and that with HP-β-CD and SBE-β-CD were AL. The solubility of andrographolide could be lower in higher concentration ofβ-CD which might be due to a steric hindrance of hydrophilic action between (3-CDs which prevented andrographolide from entering the CD cavity. The solubility of andrographolide was markedly enhanced by either HP-(3-CD or SBE-β-CD. It could be concluded that andrographolide could form stable complexes withβ-CDs according to the stability constants.Various methods were employed to prepare the inclusion complexes of andrographolide with P-CDs. Then the dissolution profiles of the inclusion complexes were determined and compared with those of original andrographolide and physical mixtures. The results suggested that the inclusion complexes obviously enhanced the dissolution rate of andrographolide.Binary systems of andrographolide withβ-CDs prepared by various methods were characterized by DSC, XRD and FTIR. It was confirmed that the inclusion complexes of andrographolide withβ-CDs prepared by all the various methods were formed.