| 摘要: | 本論文實驗的研究方向是討論蔗糖的多型晶體。一般市面上的蔗糖有一吸熱峰於攝氏189度。但是文獻指出，有另一個吸熱峰位於攝氏150度附近，其出現原因可能是因為鹽類的殘留、含水、不純、非晶態等。目前我們可以用糠醇作為反溶劑製造出蔗糖的另一形態位於攝氏150度附近的多型晶體。在掃描式熱差分儀中，可以看到一吸熱峰於攝氏140-170度。紅外線吸收光譜、粉末X光繞射儀與X光單晶繞射儀，鑑定出官能基-CH2-OH於波長1000-1200 cm-1有改變，fructofuranose ring 與分子內的氫鍵作用於(111), (-112), (003), (112)上發生位移。在近一步以SSNMR來分析結構於chemical shift 60-70 ppm有所不同，其官能基也與之前的儀器所表現出來的數據相似。KF與ICP-AE用於分析蔗糖中的水含量約為0.1-1.5w/w%與Na+, K+離子濃度約為1-5 ppm。Hot stage microscope可以觀察到蔗糖於不同的型態下有著不同的熔點，攝氏150-168與180-200度。最後將新型態的蔗糖運用在藥物的賦型劑為上。實驗結果初步說明了新型態的蔗糖在溶解度與溶解速率上的影響。 在另一個研究主題乙醯氨酚（acetaminophen） Form I，只要是以initial co-solvent screening的系統方式尋找多型晶體。其中以co-solvent中，THF + acetone與 THF + acetonitrile 可以得到長寬比為7.0與7.3的乙醯氨酚固體。但是經由掃描式熱差分儀鑑定後，其型態還是Form I其熔點為攝氏169度。然而THF + acetone中所得到的晶體是一twinned crystal。THF + N-butyl alcohol, THF+DMF, methanol + DMSO, methanol 1,4-dioxane, methanol + ethanol, ethanol +1,4-dioxane, DMSO + benzyl alcohol, and DMF + benzyl alcohol 系統中，其乙醯氨酚會水解與氧化成p-aminophenol與 p-benzoquimemonoimine的orange-red 溶液。雖然在這次研究中，沒有發現新的乙醯氨酚多型晶體。但是，對於製藥製程所需也提供了許多有價值的數據如溶解度，晶貌，多型晶體等。 Our experiments were focused on the study of the polymorph of sucrose. Normally, sucrose has an endotherm at 189oC. But in literatures, sucrose has another endotherm at 150 oC which was believed to be influenced by salt residues, water content, impurity, and crystallinity. We use an anti-solvent method to obtain sucrose solids and their polymorphism was characterized. We found a way to re-crystallize sucrose by furfuryl alcohol as an anti-solvent. The differential scanning calorimetry (DSC) thermogram of it demonstrated only one endotherm around 140o-170oC. The FT-IR spectrum, the powder X-ray diffractogram and the single crystal X-ray crystal had all pointed to the existence of polymorphs with different degree of conformational disorder about the -CH2-OH functional group, with a vibration band at 1000-1200 cm-1, in the fructofranose ring. The intramolecular hydrogen bonds were located near the reflections of (111), (-112), (112) and (003). SSMNR showed the chemical shift at 60-70 ppm having a 2-3 ppm shift pointing to the same functional group (-CH2-OH) with others instruments. KF and ICP-AES were used to determine the water content of 0.1-1.5w/w% and Na+, K+ ions about 1-5 ppm. The hot stage microscopy revealed the presence of two kinds of sucrose with melting points of 150o-168oC and 180o-200oC. Finally, we also investigated the potential application of the conformational sucrose polymorph sucrose in drug release. The experimental results showed that sucrose form II could indeed affect the dissolution rate of vitamin C. For initial co-solvent screening of acetaminophen a systematic method was utilized to find a new acetaminophen polymorph. Although the aspect ratios of crystals grown in THF + acetone and THF + acetonitrile were 7.0 and 7.3 respectively, the DSC scan showed that they were again the Form I acetaminophen. However, acetaminophen re-crystallized from THF + acetone system produced twinned crystals. The literature showed that Form II and Form III paracetamol preparation were generated by heterogeneous or secondary nucleation. The combinations of THF + N-butyl alcohol, THF+DMF, methanol + DMSO, methanol 1,4-dioxane, methanol + ethanol, ethanol +1,4-dioxane, DMSO + benzyl alcohol, and DMF + benzyl alcohol grave light pink or pink (orange-red) solution at 25 oC with hydrolysis (p-aminophenol) and oxidation (p-benzoquimemonoimine) of acetaminophen. However, acetaminophen re-crystallized from crystal-free mother liquor was produced by homogeneous nucleation. However, we had provided a lot of engineering data for drug development. These were our major contributions of acetaminophen crystallization process. |
