Preparation and characterization of andrographolide solid dispersion formulation

• Main Authors: Yu-Kai Liang, 梁育楷
• Other Authors: Yu-Tse Wu
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/22785887757053780715

碩士 === 高雄醫學大學 === 藥學系碩士班 === 105 === The study aimed to develop solid dispersion system of andrographolide (AG) to improve the dissolution and oral bioavailability. Solid dispersions were prepared by solvent evaporation method. And the optimized formulation of solid dispersion would be observed the crystal state and the chemical bonding between active ingredient and carriers. The permeability properties would be checked by everted intestinal test. Finally, the pharmacokinetics studies of rats would be conduct to prove the promotion of oral bioavailability. To optimized the formulation of solid dispersion, PEG 6000, Poloxamer 407, PVP K30, PVP K15 and PVP K90 were chosen as the carrier to evaluate the drug releasing. From the results of dissolution, the AG with PVP K30 demonstrated the best dissolution rate and was chosen for further formulation optimizing study. In the optimizing experiment, Cremophor EL or Tween 80 was added to the PVP K30 formulation. From the dissolution result, the 1:7:1 (w/w/w) of AG:PVP K30:Cremophor EL was the optimized formulation. The optimized one showed about 80% release of AG at 5 minute. In addition, comparing to AG powder, the release performance of the optimized formulation was about 16-, 2- and 4-fold higher at 5, 120 minutes and dissolution efficiency, respectively. And the results of solubility test, the optimized formulation improve the solubility about 1.5- and 1.3-fold comparing with AG and physical mixture. Moreover, differential scanning calorimetry analysis showed the optimized formulation presented amorphous state. And Fourier transform infrared spectroscopy analysis showed that there was no interaction between AG, PVP K30 and Cremophor EL. In everted intestinal test, the results showed the optimized formulation improve the permeability properties about 2-, 2- and 3-fold of duodenum, jejunum and ileum comparing with AG. At last, the pharmacokinetic studies showed solid dispersion improved relative bioavailability to 2.99-fold. And 100 mg of the optimized formulation had the similar t1/2, Cmax, AUC0-t and AUC0-∞ comparing with AG. To sum up, the solid dispersion of AG successfully overcame the solubility and permeability, also improved the oral bioavailability.