臺灣博碩士論文加值系統

本實驗主要目的是利用田口直交表和23全因子試驗設計法評估以擠壓搓圓方式製備ketoprofen圓粒產品之可行性。 根據ANOVA試驗結果顯示，水含量和黏合劑含量會影響圓粒的產率，而搓圓速度則是影響圓粒圓度之重要改變因子。 以底部噴霧方式及Wurster筒流動床機器裝置使用，並且以乙基纖維素乳膠(Surelease®)作為包覆圓粒的控釋材質，可成功地得到最適宜化的圓粒處方。 由熱分析結果顯示，ketoprofen藥品粉末與本實驗中所使用的賦形劑並不會有交互作用產生。水不溶性藥品的溶解度變化對溶離評估是一個很重要的參數，在本實驗中，ketoprofen在不同pH值及不同界面活性劑(如SLS、PVP K30)之溶解度已全面性評估，實驗結果顯示，溶離媒液中含有SLS、PVP K30可以增加ketoprofen釋出情況。 所有處方與原廠藥品Oruvial 200®以f1和f2溶離曲線比對符合因子，實驗結果顯示，所製得之處方F-S 20所製備之圓粒相似於Oruvial 200® 在pH6.8溶離媒液之溶離曲線。 綜合實驗結果顯示，使用Wurster fluid bed 機器，並且以乙基纖維素乳膠(Surelease®)作為包覆圓粒的控釋材質來製備ketoprofen控釋圓粒劑型在本實驗中是可行的。

The objective of this study was to evaluate the feasibility of the preparation of ketoprofen pellets by extrusion-spheronization method using Taguchi orthogonal and 23 full factorial experiment design. According to the ANOVA test, the results showed that amount of water content and amount of binder content have a significant effect on the yield, while the important variables which influence the roundness of pellets seem to the spheronization speed. Successively, the optimized pellets were coated with an ethylcellulose pseudolatex preparation (Surelease®) in a fluid bed coating machine using a bottom spray and a Wurster column. The thermograms showed that no interaction was occurring between ketoprofen powder and excipients. The solubility behavior of water insoluble drug is an important parameter for dissolution evaluation. In this study, the solubility of ketoprofen was well estimated by the sample additive model for the effect of various pH values and different surfactants (SLS, PVP K30). The results displayed that dissolution medium containing SLS and PVP K30 were increased condition for ketoprofen release. Dissolution profiles of all formulation including Oruvial 200® were compared by f1 and f2 fit factors. The results showed that dissolution profiles of F-S 20 formulation was the same as Ourvil 200® in the pH 6.8 dissolution medium. Therefore, the preparation of ketoprofen pellets coated with Surelease® by Wurster fluid bed were feasibile in this study.

表一 製藥工業常使用的緩釋性膜衣包覆材料-------------------------------------19
表二 Surelease 之主要組成成份-----------------------------------------------19
表三 L16（215）直交配置表（orthorgonal table）------------------------------27
表四 23複因子試驗各效應之直交係數-------------------------------------------30
表五 23複因子試驗各效應之計算組合-------------------------------------------30
表六 利用Taguchi orthorgonal table (田口直交表)製備ketoprofen圓粒及其各種變因所代表意義和level-------------------------------------------------------------40
表七 以23複因子實驗設計法製備圓粒之所代表意義和level------------------------41
表八 23 full factorial experimental design實驗設計模式----------------------41
表九 擠壓搓圓製備圓粒之條件-------------------------------------------------42
表十 擠壓搓圓製備圓粒之處方-------------------------------------------------42
表十一 直接利用流動層噴霧造粒乾燥機來進行圓粒藥層處方-----------------------43
表十二 圓粒進行圓粒控釋層包覆之流動床控制變因-------------------------------43
表十三 Ketoprofen於pH 1.2溶離媒液定量方法之同日間精密度之分析結果-----------66
表十四 Ketoprofen於pH 1.2溶離媒液定量方法之異日間精密度之分析結果-----------66
表十五 Ketoprofen於pH 6.8溶離媒液定量方法之同日間精密度之分析結果-----------68
表十六 Ketoprofen於pH 6.8溶離媒液定量方法之異日間精密度之分析結果-----------68
表十七 所有處方中圓粒膠囊之含量均一度試驗結果-------------------------------70
表十八 A (水含量)及L (搓圓速度)之High level (+)或Low level (-)所得到不同的圓度( E value )-----------------------------------------------------------------80
表十九 A (水含量)及B (黏合劑含量)之High level (+)或Low level (-)所得到不同的圓粒之產率( yield )-----------------------------------------------------------80
表二十 Taguchi orthogonal experiment design圓粒圓度之變方分析表-------------81
表二十一 Taguchi orthogonal experiment design圓粒圓度之殘差值---------------81
表二十二 Taguchi orthogonal experiment design圓粒產率之變方分析表-----------83
表二十三 Taguchi orthogonal experiment design圓粒產率之殘差值---------------83
表二十四 23複因子實驗設計法圓粒圓度之變方分析表-----------------------------86
表二十五23複因子實驗設計法圓粒圓度之殘差值----------------------------------86
表二十六 23複因子實驗設計法圓粒產率之變方分析表-----------------------------89
表二十七 23複因子實驗設計法圓粒產率之殘差值---------------------------------89
表二十八 製備ketoprofen控釋圓粒劑型之Surelease®產率分析結果-----------------91
表二十九 原廠(Oruvial 200)市售品與ketoprofen 圓粒自製品於pH 1.2溶離媒液之溶離釋出%，並以fit factors f1和f2之比較-------------------------------------------93
表三十 原廠(Oruvial 200)市售品與ketoprofen 圓粒自製品於pH 6.8溶離媒液之溶離釋出%，並以fit factors f1和f2之比較-------------------------------------------98

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