薑黃素微丸製備及藥物動力學評估

Preparation and pharmacokinetic evaluation of curcumin mini-dripping pills

賴思辰(Szu-Chen Lai)

指導教授 ： 蔡東榮

高雄醫學大學/藥學院/藥學研究所/碩士(2012年)

摘要

Curcumin是薑科薑黃屬植物(Curcuma longa)之主要活性成分，是一種非親水性的多酚類化合物。curcumin本身具有許多藥理成分，包括:抗發炎、抗氧化、抗腫瘤已及抗菌等活性，但這些藥理活性成分均因為薑黃素本身難溶於水的性質而大受影響，其口服生體可用率小於1%。本篇利用固體分散劑型-微丸，以期改善其水溶解度及提高口服生體可用率。
本篇實驗利用23實驗設計法來設計curcumin微丸之處方，設定三個變因:curcumin之含量、界面活性劑- Cremophor EL含量、輔助界面活性劑- PEG 400含量，及兩個level (High & Low)，製作出八個處方，再將此八個處方去分析物化性質，包括檢測: 微丸品質、溶解度分析、溶離程度百分率、示差掃描熱分析、掃描式電子顯微鏡，最後選擇處方六來進行curcumin微丸之活性評估，進行紐西蘭大白兔之口服藥物動力學實驗。
實驗結果發現curcumin微丸之溶解度比起curcumin原料藥大約可以提高50倍，兩小時溶離實驗發現其curcumin釋出累積量可以達到curcumin原料藥約60倍，且由示差熱掃描分析及掃描式電子顯微鏡可以看出經由劑型改善之後的薑黃素均以非晶型狀態存在，增加其水溶解度以及溶離釋出累積百分比。動物實驗結果顯示，薑黃素微丸能夠提高其相對生體可用率達15倍。

關鍵字

薑黃素 ； 薑黃素(curcumin)微丸 ； 固體分散劑型 ； 藥物動力學

並列摘要

Curcumin is a hydrophobic polyphenol deriving from the rhizoma of tumeric (Curcuma Longa), it possesses lots of pharmacological activities, such as anti-tumor, anti-oxidant, anti-inflammatory, anti-microbial properties. Nevertheless, these pharmacological activities of curcumin are limited by its poor aqueous solubility (below 1μg/ml). Thus, here we developed a solid dispersion, the mini-dripping pills, which could enhance the aqueous solubility and the dissolution rate of curcumin. We applied the experimental design with 3 factors (curcumin contents, cremophor EL, PEG400) and 2 levels to evaluate the differences between the various ratios of pill components.
The detections of physical and chemical properties of curcumin mini-dripping pills include weight variation, diameters, differential scanning calorimeter, aqueous solubility test, curcumin concentration analysis by HPLC, the comparison of the dissolution rates between curcumin mini-dripping pills and curcumin powders, and the morphology analysis of curcumin mini-dripping pills by scanning electron microscope, and regard to the formulation its in-vitro dissolution, we choose the formulation 6 to , we evaluated the curcumin mini-dripping pills in New Zealand rabbit compared with the curcumin powder.
The diameters of curcumin mini-dripping pills were 10 mm~20 mm and the average weight was about 2 mg per pill. The result of our study shows that the aqueous solubility of curcumin mini-dripping pills was about 50-fold higher than curcumin powders. At the meanwhile, we found that the dissolution rate of curcumin mini-dripping pills in pH 1.2 medium was around 60-fold higher than curcumin powders as well.

並列關鍵字

Curcumin ； curcumin mini-dripping pills ； solid dispersion ； Pharmacokinetics

參考文獻

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