醋酸纖維素共混聚合物的薄膜探討及其應用之研究

Study of Cellulose Acetate Blended Films and Its Application

薛桂如(Guei-Ru Shiue)

指導教授 ： 林文貞

國立臺灣大學/醫學院/藥學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.01500

摘要

醋酸纖維素是一種具有高生物相容性的乙醯化纖維素聚合物，由於其毒性低、安全性高且價格低廉等優點，目前已廣泛應用在藥物遞送系統上，但本身不溶於水，對於酸鹼安定性高，所以無法在胃腸道被分解，若用來包覆錠劑則藥物無法直接穿透半透膜釋出，故本實驗藉由醋酸纖維素共混水溶性孔洞形成劑來改善上述問題，因水溶性孔洞形成劑可在含水媒液中溶出，進而使醋酸纖維素薄膜產生孔洞結構，此多孔性膜衣可達到控釋藥物的目的。

本實驗第一部分先探討由溶媒法製備的醋酸纖維素與孔洞形成劑(聚乙烯吡喀酮與聚乙二醇4000)之共混薄膜，使用FT-IR、DSC與機械性質實驗來研究薄膜的特性。此外藉由水洗出孔洞形成劑的方法來製備孔洞薄膜，並進行擴散實驗，使用孔隙度及SEM照片觀察孔洞外觀及大小。在共混薄膜中，FT-IR的結果顯示醋酸纖維素與這兩種孔洞形成劑皆有極微弱的氫鍵作用；根據DSC結果可發現醋酸纖維素與聚乙烯吡喀酮可混溶，但不與聚乙二醇混溶；在機械性質上，當這兩種孔洞形成劑添加量為≦30%時，對醋酸纖維素薄膜有較佳的塑化效果。另外，在孔洞薄膜的擴散結果可發現，由聚乙二醇所形成的孔洞薄膜有較快的藥物擴散速率，且有較大的孔隙度/扭曲度比值(ε/τ)。

第二部分是利用沾黏包覆方式將含有水溶性孔洞形成劑的醋酸纖維素膜衣包覆在無水茶鹼錠劑表面，製成微孔性控釋錠，使得藥物可經由孔洞或相連性的通道穿透，而達到控釋效果。經由SEM照片可得知，不論添加的孔洞形成劑是聚乙二醇或聚乙烯吡喀酮，膜衣上的孔洞大小與數目會隨著兩者的添加比例增加而增加。此外，在體外溶離試驗的結果發現，藥物的釋放速率會隨著孔洞形成劑添加比例的增加而增加，且聚乙二醇較聚乙烯吡喀酮快。而從薄膜特性研究結果發現聚乙二醇較聚乙烯吡喀酮容易被水完全洗出，顯示藥物的釋放速率與孔洞形成劑的洗出難易與完全與否有相當的關連性。此外，添加親水性塑化劑glycerin、PG及PEG400可促進無水茶鹼穿透CA50%/K1550%膜衣；CA60%/PEG400040%與CA70% /PEG400030%配方膜衣中，PEG400對於藥物的促進效果較為明顯，然而glycerin卻是抑制的。

關鍵字

醋酸纖維素 ； 聚乙二醇 ； 聚乙烯吡喀酮 ； 共混聚合物

並列摘要

Cellulose acetate (CA) is an esterified polymer of cellulose with high biocompatibility. Nowadays, it’s widely used in drug delivery system due to its low toxicity, good safety and low cost. However, it’s water insoluble, non-sensitive to pH, and not degradable in GI tract. The drug can not directly release through the semi-permeable film of CA. In this study, we blended CA with water soluble pore-forming agents to overcome this issue. The pore-forming agents in CA blended films were leached out in aqueous medium and created porous structure to control drug release.

In the first part, the blended films consist of CA and pore-forming agents (PVP K15 and PEG4000) were characterized by FT-TR, DSC and mechanical tests.The porous films were prepared by solvent-casting-leaching method. The FT-IR showed that there existed a weaker interaction between CA and these two pore-forming agents. CA was miscible with PVP K15 but immiscible with PEG4000 based on DSC data. In mechanical tests, these two pore-forming agents showed a better plasticized effect on CA films when under 30% pore-forming agent was added. From SEM pictures, more and bigger pores were observed for porous films blended with more pore-forming agents. These results were consistent with the diffusion data where the permeation coefficient (P) was increased with increasing pore-forming agents.

In the second part, microporous controlled released tablets were prepared by dip-coating method. The pore-forming agents were leached out when tablets exposed to aqueous medium. The drug was released from the inter-connected pores and channels. From in vitro release study, the drug release rate increased with increasing pore-forming agents and PEG4000 enhanced more drug release than PVP K15 did. This was because that PEG4000 can be easily and completely leached out. Moreover, the effect of three different hydrophilic plasticizers (glycerin, PG and PEG400) on drug release rate was investigated. It was found that all plasticizers enhanced drug release from CA50%/K1550% coated tablets. For CA60%/PEG400040% and CA70%/PEG400030% coated tablets, PEG400 played the most effect on increasing drug release, oppositely, glycerin retarded drug release.

並列關鍵字

Cellulose acetate ； PEG4000 ； PVP K15 ； polymer blends

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