薑黃素固體分散製劑的製備及其抗氧化的評估

Preparation, Characterization and Antioxidative Evaluation of Curcumin Solid Dispersion

吳孟穎(Meng-Yiing Wu)

指導教授 ： 蔡東榮

高雄醫學大學/藥學院/藥學研究所/碩士(2010年)

摘要

薑黃素為薑科薑黃屬植物(Curcuma longa)的主要活性成分，是一個多酚類的化合物，具有許多的藥理作用，包括抗發炎、抗癌、抗病毒以及擁有抗菌的活性。然而，薑黃素是水難溶性的物質而且其口服生體可用率很低。固體分散劑型可以降低藥品的粒子大小並且可以改善藥品的濕潤性。因此，本篇研究利用固體分散的技術以製備藥品的配方。
薑黃素的固體分散劑的製備方式為採用溶媒揮發法。此外，本篇論文採用2(3)實驗設計法，設定的三個變因為Polymer type: PVP K30/Eudragit® EPO，薑黃素與Polymer的比例：1:7/1:9以及是否加入citric acid monohydrate，選出最佳的處方，並探討其物化性質，包括以穿透式電子顯微性、示差掃描熱分析、傅立葉轉換紅外光譜儀來觀察。薑黃素固體分散製劑對抗氧化的活性影響則是利用清除DPPH自由基的能力來評估。
實驗結果發現薑黃素固體分散製劑的水溶解度約為1368 μg/mL以及體外溶離試驗的釋出累積量約為原先的70倍，明顯改善薑黃素的溶解度及體外溶離，且物化性質的觀察呈現非晶形狀態，抗氧化情形則可發現在水及tris-HCl buffer中，薑黃素固體分散劑皆具有清除DPPH自由基的作用，而原料藥則不具有清除DPPH自由基的作用。

關鍵字

薑黃素 ； 固體分散製劑 ； 抗氧化

並列摘要

Curcumin, a polyphenol active ingredient, had several pharmacological activities, including anti-inflammatory, anticarcinogenic, anti-virus and antiseptic activities. However, Curcumin was insoluble in water and had low oral bioavailability. Solid dispersion which could reduce drug particle size improved drug wettability.
Therefore, we used solid dispersion technique to prepare formulations in our study, and we also used 2(3) factorial designs to choose the best formulation. Three factors were the polymer type (PVP K30 and Eudragit® EPO), the ratio of Curcumin: polymer (1:7 and 1:9) and added citric acid monohydrate or not. Solid dispersions of Curcumin were obtained by solvent evaporation method. Physicochemical characterizations of the prepared solid dispersions were studied by differential scanning calorimetry and fourier transform infrared spectroscopy. In the antioxidative part, we used DPPH free radical-scavenging activity to evaluate. The solvents we used here were deionized water and tris-HCl buffer.
In the dissolution studies, the solubility and dissolution of Curcumin solid dispersion showed better than Curcumin. Using solid dispersion improved the in vitro dissolution of Curcumin for about 70 folds. Physicochemical characterizations of the prepared solid dispersions we found had presented an amorphous product. In the assay of DPPH free radical-scavenging activity, we found that Curcumin solid dispersion both had the ability to scavenge free radical in deionized water and tris-HCl buffer. However, Curcumin didn’t have the ability to scavenge free radical in deionized water and tris-HCl buffer.

並列關鍵字

Curcumin ； Solid Dispersion ； Antioxidation

參考文獻

Aggarwal B.B., Harikumar K.B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009;41:40-59.

Aggarwal B.B., Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci 2009;30:85-94.

Anand P., Kunnumakkara A.B., Newman R.A., Aggarwal B.B. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-818.

Chow C.K. Vitamin E and oxidative stress. Free Radic Biol Med 1991;11:215-232.

Das D., Bandyopadhyay D., Bhattacharjee M., Banerjee R.K. Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radic Biol Med 1997;23:8-18.