評估膜衣機械特性並利用膜衣包覆圓粒製備懸浮胃滯留劑型
Evaluation of mechanical properties of polymer films for preparation
of coated pellet as a floating drug delivery system
中文摘要 本研究探討 (1) 藉由動態機械分析儀的實驗結果得知的膜衣機械特性與膜衣實 際包覆在圓粒後的懸浮能力之相關聯性。(2)擬發展以含藥的圓粒為核心，外層 包覆膜衣的理想懸浮胃滯留劑型。 首先，利用動態機械分析儀了解 Eudragit® RS 30D,、RL 30D 、NE 30D 、 Surelease® 和 EC 等聚合物撘配不同塑化劑於乾燥及濕潤情況下的膜衣強度及 延展性等機械特性。以 Surelease®和 EC 製備的膜衣與 Eudragit®系列相比顯得較 脆且易碎。Eudragit® NE 30D 則是不論在乾燥或溼潤的情況下都有非常好的延展 性。當 Eudragit® RS 30D 和 RL 30D 以 15% TEC 或 DEP 為塑化劑時，會因塑 化劑在水溶液中溶出造成濕潤膜衣的延展性下降。 當懸浮胃滯留劑型以 Eudragit® RL 30D 為膜衣時，圓粒擁有優異的懸浮能力但 藥物溶離卻無法達到緩釋的效果。此外，Eudragit® RL 30D 以 15% DEP 和 DBP 塑化時較 TEC 擁有較佳的懸浮能力。利用 Eudragit® RS 30D 為膜衣時藥物可緩 慢釋出。然而，因 Eudragit® RS 30D 的水份通透度可能不足以產生足量的 CO2 導致圓粒無法懸浮於液面。為了解決這些問題，因而將 Eudragit® RL 30D 和 RS 30D 以 1:1 的比例做為懸浮藥物傳遞系統的膜衣。雖然因 Losartan 為易溶於水 的藥物導致溶離仍然太快，但包覆上 Eudragit® RL 30D 混合 Eudragit® RS 30D 為膜衣的懸浮系統仍可能有運用在難溶性藥物的潛力。 由以上的實驗結果可知雖然有其它因素例如水份通透性及模式藥物的溶解度等 需要考慮，動態機械分析儀仍然可以當作了解膜衣特性、發展這類懸浮胃滯留劑 型時的預試驗。 英文摘要
The objective of this study was to (1) find a possible correlation between mechanical characteristics determined by DMA and floating properties measured on coated pellets from studies (2) develop and evaluate ideal floating drug delivery systems (FDDS) consisting of a drug-containing core pellet with a polymeric coating.
The mechanical properties (strength and elongation) of acrylic (Eudragit® RS 30D, RL 30D or NE 30D) and cellulosic (Surelease®、EC) polymers with different plasticizer type were studied by the dynamic mechanical analyzer in the dry and wet state. Films prepared from Surelease® and EC resulted in brittle films when
compared to the acrylic films. Films of Eudragit® NE 30D were very flexible in both the dry and wet state. Because the plasticizer leached from the polymeric films during
exposure to the aqueous medium, wet Eudragit® RS 30D and RL 30D polymer films plasticized with 15% TEC or DEP result in decreasing elongation.
When Eudragit® RL 30D was the polymer coating for the floating system, the pellets had excellent floating ability but the sustained release properties could not be
achieved. Besides, Eudragit® RL 30D plasticized with 15% DEP and DBP had better floating ability than TEC. The system using Eudragit® RS 30D as polymeric
membranes had sustained release properties. However, the pellets did not float because Eudragit® RS 30D might not be permeable enough for medium to generate sufficient amount of CO2. To solve these problems, a 1:1 ratio of Eudragit® RL 30D and RS 30D plasticized with 15% DEP was used as the polymeric membrane in the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, the FDDS coated with Eudragit® RL 30D combined with RS 30D might have potential use for oral delivery of water insoluble drug.
Based on these results, although there are some other factors such as water
permeability and the solubility of model drug need to be considered, DMA can be a preliminary screening tool to identify film properties for application as floating systems.
