Coenzyme Q10滴丸製備與藥物動力學評估

Preparation and Pharmacokinetic Evaluation of Coenzyme Q10 Dripping Pills

徐婕凌(Chieh-Ling Hsu)

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

Coenzyme Q10 , CoQ10具有許多藥理作用，包括輔助治療高血壓、心衰竭、狹心症及帕金森症等。CoQ10為水難溶性的物質且口服生體可用率極低。因此，本研究利用固體分散原理製備CoQ10滴丸劑型，欲增加水難溶性藥品之溶解度與溶離，並提高生體可用率。
以23實驗設計法，三個變因為藥物含量、poloxamer 407含量做為界面活性劑及油的種類(橄欖油或Capryol 90)做為油相基劑，探討其物化性質，包括以溶離試驗測其溶離百分比、溶解度試驗、重量差異度試驗測其重量是否具均一性、掃描式電子顯微鏡觀察粒子外觀、式差掃描熱分析來觀察物質熱焓量變化，選擇最佳CoQ10滴丸處方 (60 mg/kg)及粉末 (1000 mg/kg)口服給予紐西蘭大白兔，測得藥物動力學參數並比較粉末與滴丸劑型間的生體可用率。
實驗結果發現CoQ10滴丸劑型於pH 1.2 水溶液的溶解度為70.88 μg/ml比CoQ10粉末增加了97倍，體外溶離試驗的釋出累積量約為原先的22倍，滴丸劑型明顯改善CoQ10的溶解度及體外溶離釋出，經掃瞄式電子顯微鏡觀察處方皆呈現非晶形狀態，再以式差掃描熱分析加以佐證藥物確實能以非晶型存在於基質當中，藥物動力學方面可知強飼CoQ10滴丸相較CoQ10粉末高出101倍的生體可率。

關鍵字

輔酶Q10 ； 輔酶Q10 (Coenzyme Q10)滴丸 ； 固體分散劑型 ； 藥物動力學

並列摘要

Coenzyme Q10, CoQ10, had several pharmacological activities, including antioxidant, improvement of cardiac bioenergetics, enhancing the immune system. However, CoQ10 was insoluble in water and low bioavailability. This study aimed to develop dripping pills of CoQ10 with high aqueous solubility, dissolution rate and bioavailability.
By 23 factorial designs, CoQ10 dripping pills were prepared by CoQ10, poloxamer 407 as surfactant and oil type (olive oil or capryol 90) as oil base. The physicochemical properties of each formulation were characterized by solubility test, dissolution test, weight variation test, scanning electron microscope (SEM) and differential scanning calorimetry (DSC). The pharmacokinetic study of CoQ10 dripping pills (60 mg/kg), in comparison to a powder of CoQ10 (1000 mg/kg), was also carried out in rabbits after a single oral dose.
CoQ10 dripping pills formulation exhibited high solubility (70.88 μg/ml) and 22-fold high release percentage than the powder CoQ10. In all CoQ10 dripping pills formulations, CoQ10 existed mainly as an amorphous form as determined by DSC. In the pharmacokinetics study, CoQ10 dripping pills showed 101-fold high bioavailability than powder.

並列關鍵字

Coenzyme Q10 ； CoQ10 dripping pills ； solid dispersion ； pharmacokinetic

參考文獻

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