| Summary: | 碩士 === 高雄醫學大學 === 藥學研究所 === 97 === Monacolin K is the major secondary metabolite of Red yeast rice, which mainly uses in lowering the cholesterol; Monacolin K is a poorly water-soluble drug, which is one of the reasons that it has a low bioavailability. The objective of this study is using the technology of solid dispersion to make red yeast rice Dripping Pills form to increased Monacolin K solubility and bioavailability. The 23 full factorial experimental design was used to investigate the different factors (surfactant, co-surfactant, lipid) in preparing Dripping Pills, and to look for physiochemical properties, including monitor Monacolin K concentration by HPLC, to observe the amorphous and changing of structure by Differential scanning calorimetry and Fourier transform infrared spectroscopy, to observation outward appearance change of Scanning electron microscope. The final experimental design from was evaluated with regard to its in vitro dissolution, and bioavailability in Sprague-Dawley (SD) rat compared with the red yeast rice powder or market capsule.
Comparing with market capsule (45.27 ± 4.53, 1.52 ± 1.14 μg/ml), Monacolin K Dripping Pills (96.85 ±7.75 μg/ml) has better solubility. Differential scanning calorimetry recording of the pure Monacolin K exhibits a sharp endothermic peak around 173 ºC, but Monacolin K Dripping Pills resulted in a complete suppression of the drug fusion peak. Suggest that Monacolin K has completely converted into an amorphous state; Fourier transform infrared spectroscopy recording Monacolin K bedding bag in the carrier, the structure dose not have the significance change. Scanning electron microscope recording after design, Dripping Pills has the surface to be smooth, pellet circle entire, simultaneously reduces the crystallization. In phosphate buffer (pH6.8), Monacolin K powder dissolution was quite low (3.74% within 12 hr). However, after being prepared as a Dripping Pills, substantially was improved (about 57% in 1 hr), and became greater than the dissolution of market capsule (about 25% in 12 hr). This is mainly because in the Dripping Pills, it was effective to increase Monacolin K solubility and dissolution. In SD rat pharmacokinetics study, the maximum plasma concentration of Monacolin K of Dripping Pills (Cmax:1.9505 ± 0.4419 μg/ml) increases three times than those in red yeast rice powder (0.50154 ± 0.1136 μg/ml). We can conclude that Dripping Pill form can increase its both water solubility and oral bioavailability and clinical efficacy.
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