Fluoxetine 微乳劑型之經皮給藥研究

Study of fluoxetine-loaded microemulsion for transdermal drug delivery

林以鈞(I-Chun Lin)

指導教授 ： 吳寶珠

高雄醫學大學/藥學院/藥學系碩士班/碩士(2019年)

摘要

Fluoxetine為臨床上常用的憂鬱症用藥之一，商品名為百憂解，在藥理的分類主要為選擇性血清素再吸收抑制劑(SSRI)，主要的給藥方式為口服錠劑及膠囊。Fluoxetine也可以用於治療其他疾病，如強迫症、恐慌症。然而，Fluoxetine卻存在許多副作用，像是性功能障礙、頭痛、失眠等。
本藥品經口服後，被CYP2D6代謝，有些學者認為Fluoxetine的副作用與首度代謝效應有關，造成血中濃度波動過大的現象產生。因此本研究嘗試以經皮給藥方式投與Fluoxetine，藉此減少首度代謝效應。
本研究使用微乳劑作為載體遞送Fluoxetine，以Franz cells作為實驗模型，並且選用Tween 80, Brij 35, Cremophor RH40, Labrasol, Vit. E TPGS作為界面活性劑，輔助界面活性劑選用Transcutol及ethanol。由於fluoxetine的水溶解度不佳，因此本研究設計O/W型微乳劑來遞送fluoxetine。
研究結果顯示，最佳處方在體外24小時累積穿透量約為對照組的114倍，體內藥物動力學則在給藥24小時候呈顯穩定的血中濃度。長期安定性則顯示在溫度25 ± 2°C、相對溼度60 ± 5%保存條件下，兩個月後劑型仍可以安定存放，含藥量仍維持99%。因此，微乳劑型可做為Fluoxetine經皮給藥方式的優良載體。

關鍵字

百憂解 ； 憂鬱症 ； 經皮給藥系統 ； 微乳劑

並列摘要

Fluoxetine is a usually use medicine for depression treatment, and commercial product name is Prozac. The pharmacology classification of Fluoxetine is selective serotonin reuptake inhibitor (SSRI), primary route of administration is oral tablets and capsules. Fluoxetine can be applied for another disease, such as obsessive-compulsive disorder and panic disorder. But there are many side effects exist, like sexual dysfunction, headache, insomnia.
After oral administration, fluoxetine is metabolized by CYP2D6 , some scholars think that these side effects may be associated with variable plasma drug concentration caused by fluoxetine hepatic first-pass metabolism. So we decide to develop the transdermal drugs delivery for fluoxetine to avoid the first-pass metabolism.
Our study use microemulsions as the vehicle to deliver fluoxetine. We use Franz cells as the experiment model, choose the Tween 80, Brij 35, Cremophor RH40, Labrasol, Vit. E TPGS as the surfactant. For co-surfactant, we choose Transcutol and ethanol. Because the solubility of fluoxetine is not very well in water , so we design the O/W type microemulsions to deliver fluoxetine.
As a result, our formulation is better than control group about 114 times in 24 hours drugs accumulation. Pharmacokinetic result show that our formulation can provide the stable plasma concentration after 24 hours. For long-term stability, under 25 ± 2°C and RH 60 ± 5% condition, the formulations can still stable storage after 2 months.
We think our formulation is feasibility to transdermal deliver for fluoxetine

並列關鍵字

Fluoxetine ； Microemulsion ； Transdermal drug delivery system

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