利用微乳液系統研究有機藥物之微粒化並探討有機藥物晶型及溶解速率

Abstract

摘要 對於低水溶性或生物體利用率低的有機藥物而言，利用微乳液將有機藥物微粒化或將有機藥物的晶型轉變為水溶性較佳的晶型，以提高有機藥物在人體中的溶解速率，並達到提升生物體利用率的功效。因此本研究利用微乳液系統，這個既直接又安全的操作方式藉由改變溫度的製程來做有機藥物的改質。 本研究的目的為研究有機藥物經過微乳液系統操作後的晶型改變及溶解速率改變，並且研究各種有機藥物在離子型、非離子型的微乳液中，以及在純溶劑當中，再結晶顆粒的物理特性。我們使用了三種不同的微乳液系統以及三種純溶液系統。 經實驗發現，微乳液系統有使有機藥物轉變成水合物的趨勢。容易形成水合物的有機藥物在任何微乳液系統都可轉變成水合物（carbamazepine、piroxicam、sulfaguanidine、theophylline、nitrofurantoin、diclofenac sodium），而對於不易形成水合物的diflunisal則是在特定為乳液系統可將其轉變成水合物。 而對於具有多晶型性的有機藥物而言，微乳液系統可以將其轉變為不同於原藥的晶型。對於sulfathiazole，微乳液系統可將其從Form-IV轉變成Form-III。且sulfathiazole的溶解速率也因晶型的轉變而有所提升。 不具有多晶型性的有機藥物雖然法在微乳液系統中不會做晶型的轉變，但卻有被微粒化的趨勢。Mitotane、ibuprofen的溶解速率都因為粉體顆粒的減小而有顯著的提升。 有機藥物的物理性質隨著微乳液操作條件的不同而有所改變。利用此特性，吾人可以利用適當的微乳液系統操作有機藥物可使我們可以獲得特定的有機藥物晶型、晶貌、以及溶解速率。

Abstract For poor solubility in water or lower bioavailability organic drugs, using microemulsion systems to micronize or structurally change the drugs, is both a direct and safe method to enhance the dissolution rate and bioavailability of the drugs in the human body. In this research, the microemulsion systems were utilized with temperature changing processes to modify organic drugs. Microemulsion systems were used to change the structure and dissolution rate of organic drugs. Ionic and nonionic microemulsions and pure solvents environments were investigated. The study was aimed to correlate the structural change and dissolution rate change of organic drugs after recrystallizing from microemulsions. In the research, we found that microemulsion systems could lead organic drugs to a hydrated state. For carbamazepine, piroxicam, sulfaguanidine, theophylline, nitrofurantoin, and diclofenac sodium, every microemulsion system could be changed from anhydrate to hydrate. However for diflunisal, only specific microemulsion conditions could change to hydrated states. For drugs with polymorphism, microemulsion systems could change to different structures. Microemulsion systems could change sulfathiazole from Form-IV to Form-III and improve its dissolution rate. Microemulsion systems can also micronize organic compounds. Mitotane and ibuprofen were micronized by microemulsion system. Therefore, after microemulsion process they performed better dissolution rate. The results suggest that the microemulsion systems can cause the organic drugs to change structure or become hydrate crystals. The dissolution rates of modified crystals change depending on the conditions. Crystallization from microemulsion media enables one to obtain the drug with a predictable structure, morphology, and dissolution rate.