本文選題：水分散體制備 + Eudragit(?)L30D-55　； 參考：《浙江大學》2014年碩士論文

【摘要】：腸溶包衣已經(jīng)被廣泛用于提高對酸敏感藥物的化學穩(wěn)定性,減少胃刺激及靶向藥物在結腸釋放等領域。有機溶劑包衣是較為傳統(tǒng)的包衣技術,通過溶劑蒸發(fā)形成結構較為致密,水分不容易透過的聚合物膜。但有機溶劑包衣特別是用于微丸包衣時其較高的粘度會給包衣帶來不便,且由于有機溶劑毒性大、易揮發(fā)、易燃易爆、價格昂貴、存在潛在環(huán)境污染等缺點,其應用推廣受到了一定限制。聚合物水分散體包衣是一種以水為分散介質(zhì)的復雜體系,具有毒性低、粘性低、包衣效率高等優(yōu)點�，F(xiàn)有常用水分散體包衣液中的包衣材料分子及增塑劑分子,主要呈現(xiàn)各自聚集形成固態(tài)或半固態(tài)的球形粒子特征,增塑劑與包衣材料分子之間相互擴散產(chǎn)生分子交互作用程度不足,導致水分散體包衣膜的結構致密性不及有機溶劑膜。本研究制備了一種新型的腸溶材料水分散體。先將腸溶包衣材料Eudragit(?)L100-55溶于有機溶劑,加入增塑劑檸檬酸三乙酯(Triethyl citrate, TEC),必要時加入其他附加劑溶解,加入處方量水乳化均勻后,揮發(fā)除去有機溶劑制備得到水分散體包衣液(Eudragit(?)L100-55水分散體包衣液)。采用鑄膜法分別制備Eudragit(?)L100-55水分散體、Eudragit(?)L100-55有機溶劑、Eudragit(?)L30D-55水分散體游離膜�？疾焐鲜鲇坞x膜的外觀,以差示掃描量熱法(Differential scanning calorimetry, DSC)測定薄膜玻璃化轉變溫度(Glass transition temperature, Tg),杯法考察薄膜的透濕性能,轉籃法測定游離膜在不同介質(zhì)中的溶解性能。結果顯示,當TEC濃度同為5%時,Eudragit(?)L100-55水分散體膜的滲透性能接近于Eudragit(?)L100-55有機溶劑膜,二者的膜滲透性均明顯小于市售Eudragit(?)L30D-55水分散體膜。當TEC濃度分別為10%及20%時,Eudragit(?)L30D-55水分散體膜的Tg分別為58.17℃及50.95℃,Eudragit(?)L100-55水分散體膜的Tg分別為53.63℃及41.72℃,Eudragit(?)L100-55有機膜的Tg分別為51.70℃及32.25℃,顯示Tg的大小排序為：Eudragit(?)L30D-55水分散體膜Eudragit(?)L100-55水分散體膜Eudragit(?)L100-55有機膜。在相同濃度增塑劑條件下,Eudragit(?)L100-55水分散體膜的Tg、透濕性均低于Eudragit(?)L30D-55水分散體膜。同等條件下,Eudragit(?)L100-55水分散體膜在O.lmol/L鹽酸中溶解性明顯小于Eudragit(?)L30D-55水分散體膜,顯示其耐酸力強于Eudragit(?)L30D-55水分散體膜。以泮托拉唑鈉(Pantoprazole sodium, PAZ-Na)為模型藥物,擠出滾圓法制備含藥丸芯,流化床底噴包衣。以羥丙基甲基纖維素(Hydroxypropyl methyl celulose, HPMC)為隔離層膜材,分別以Eudragit(?)L30D-55水分散體、Eudragit(?)L100-55水分散體、Eudragit(?)L100-55有機溶液為腸溶材料,制備PAZ-Na腸溶微丸,研究腸溶包衣后微丸的耐酸力及釋藥情況。在包衣過程中,發(fā)現(xiàn)Eudragit(?)L100-55水分散體粘度低于Eudragit(?)L1100-55有機溶液,且包衣時間明顯縮短。當腸溶衣增重9%時,比較Eudragit(?)L30D-55水分散體腸溶衣微丸、Eudragit(?)L100-55有機溶液腸溶衣微丸和Eudragit(?)L100-55水分散體腸溶衣微丸的耐酸性,在0.1mol/L鹽酸耐酸力實驗中,發(fā)現(xiàn)三種腸溶微丸中藥物剩余量分別為76.21%、86.44%及85.19%。相應的,三種腸溶微丸在酸中的藥物損失量,分別為23.79%、13.56%及14.81%；當腸溶衣增重12%時,三種腸溶微丸中藥物剩余量分別為88.87%、94.52%及93.78%,相應的,三種腸溶微丸在酸中的藥物損失量,分別為11.13%、5.48%及6.22%。顯示Eudragit(?)L100-55有機膜和Eudragit(?)L100-55水分散體膜的耐酸性,明顯高于Eudragit(?)L30D-55水分散體膜。研究結果發(fā)現(xiàn),自制的Eudragit(?)L100-55水分散體,在較小的包衣增重(9%)條件下制備得到的腸溶微丸的耐酸性,接近于市售Eudragit(?)L30D-55水分散體在較大包衣增重(12%)條件下得到的腸溶微丸的耐酸性,顯示其在減少包衣材料用量及增強包衣效率上的優(yōu)勢。本課題的研究結果顯示,通過乳化蒸發(fā)法制備得到的Eudragit(?)L100-55水分散體,其腸溶膜的熱力學性質(zhì)、透濕性、溶解性及耐酸性等理化性質(zhì),均體現(xiàn)出接近于Eudragit(?)L100-55有機膜,且優(yōu)于Eudragit()L30D-55水分散體膜,同時保持了水分散體包衣快速、便捷的優(yōu)點,是一種有良好應用前景的新型包衣水分散體。
[Abstract]:Enteric coated coating has been widely used to improve the chemical stability of acid sensitive drugs, reduce the gastric irritation and the release of the target drug in the colon. Organic solvent coating is a more traditional coating technology, and evaporates to form a dense polymer membrane through solvent evaporation, but the organic solvent coating is especially used for micro coating. The high viscosity of the pellets will bring inconvenience to the coating, and because the organic solvent is toxic, volatile, flammable, explosive, expensive, and has the potential environmental pollution, its application is limited. The polymer water bulk coating is a complex system with water as the dispersing medium with low toxicity, low viscosity and coating. The coating material molecules and plasticizer molecules in the existing liquid bulk coating liquid are mainly characterized by the formation of spherical particles in solid or semi solid state, and the interaction between the plasticizer and the coating material is insufficient, which leads to the structural densification of the coating membrane. A new type of aqueous dispersion of enteric material was prepared. First, the enteric coated material Eudragit (?) L100-55 was dissolved in the organic solvent, adding three ethyl citric acid (Triethyl citrate, TEC) with the plasticizer, and adding other additives when necessary. After the emulsification of the prescription water was uniform, the organic solvent was prepared by volatilization. Eudragit (?) L100-55 aqueous dispersion, Eudragit (?) L100-55 organic solvent and Eudragit (?) L30D-55 water bulk free membrane were prepared by casting film method (Eudragit (?) L100-55 aqueous dispersion coating solution). The external view of the free membrane was investigated by differential scanning calorimetry (Differential scanning calorimetry, DSC). The membrane glass transition temperature (Glass transition temperature, Tg) was used to investigate the moisture permeability of the film. The solubility of the free film in different media was measured by the method of rotating basket. The results showed that when the concentration of TEC was 5%, the permeability of Eudragit (?) L100-55 aqueous dispersion membrane could be close to Eudragit (?) L100-55 organic solvent membrane and the membrane permeation of the two. When the TEC concentration was 10% and 20%, the Tg of Eudragit (?) L30D-55 water bulk membrane was 58.17 and 50.95, respectively, Eudragit (?) L100-55 water bulk membrane was 53.63 and 41.72, respectively, and Eudragit (?) L100-55 organic membrane was 51.70 and 32.25, respectively, when the TEC concentration was 10% and 20% respectively. The size of the Eudragit (?) L30D-55 aqueous dispersion film Eudragit (?) L100-55 aqueous dispersion membrane Eudragit (?) L100-55 organic membrane. Under the same concentration plasticizer, the Tg of the Eudragit (?) L100-55 water bulk membrane is lower than the Eudragit (?) L30D-55 aqueous dispersion film. Under the same condition, Eudragit (?) The solubility of hydrochloric acid is less than Eudragit (?) L30D-55 aqueous dispersion membrane, which shows its acid resistance is stronger than that of Eudragit (?) L30D-55 aqueous dispersion membrane. Pantoprazole sodium (Pantoprazole sodium, PAZ-Na) is used as a model drug. The extrusion pellet method is used to prepare pill core and fluidization bed spray coating. With hydroxypropyl methyl cellulose (Hydroxypropyl methyl Celulose,) HPMC) for isolation layer film, Eudragit (?) L30D-55 aqueous dispersion, Eudragit (?) L100-55 water bulk, Eudragit (?) L100-55 organic solution as enteric soluble material, PAZ-Na enteric pellets were prepared to study the acid resistance and release of micropellets after enteric coated coating. In the process of coating, the viscosity of Eudragit (?) L100-55 water bulk was lower than Eudragit (? ) L1100-55 organic solution, and the coating time was obviously shortened. When the enteric coat weighed 9%, the acid resistance of Eudragit (?) L30D-55 water dispersible enteric coated pellets, Eudragit (?) L100-55 organic solution pellets and Eudragit (?) L100-55 water dispersible enteric coated pellets were compared. In the acid endurance test of 0.1mol/L hydrochloric acid, three kinds of enteric pellets were found. The residual amount of the material was 76.21%, 86.44% and 85.19%. respectively. The drug loss of three kinds of enteric pellets in acid were 23.79%, 13.56% and 14.81%, respectively. When the enteric coat weighed 12%, the residual amount of drugs in three enteric pellets was 88.87%, 94.52% and 93.78% respectively, and the amount of drug loss of three kinds of enteric pellets in acid was 11.13%, respectively. 5.48% and 6.22%. showed that the acid resistance of Eudragit (?) L100-55 organic film and Eudragit (?) L100-55 water bulk membrane was significantly higher than that of Eudragit (?) L30D-55 aqueous dispersion membrane. The results showed that the self-made Eudragit (?) L100-55 aqueous dispersion and the acid resistance of the enteric pellets prepared under the conditions of smaller coating weight gain (9%) were close to the market Eudrag. The acid resistance of it (?) L30D-55 aqueous dispersions under the condition of large coating weight gain (12%) is shown to reduce the amount of coating materials and enhance the coating efficiency. The results of this study show that the Eudragit (?) L100-55 aqueous dispersion obtained by emulsification evaporation method, the thermodynamic properties of its enteric membrane, and the moisture permeability of its enteric membrane The physical and chemical properties, such as sex, solubility and acid resistance, are close to the Eudragit (?) L100-55 organic membrane, and are superior to Eudragit () L30D-55 water dispersions. It also maintains the quick and convenient advantages of water bulk coating, and is a new type of coating moisture bulk with good application prospect.

【學位授予單位】：浙江大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

【參考文獻】

相關期刊論文 前2條

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本文編號：1851768