吳茱萸鹼固體分散劑型之製備及其性質評估

Preparation and evaluation of evodiamine-loaded solid dispersion

黃振槐(Chen-Huai Huang)

指導教授 ： 吳育澤

高雄醫學大學/藥學院/藥學系碩士班/碩士(2018年)

摘要

本研究目的為提升吳茱萸鹼水溶解度及對酸性安定性。將吳茱萸鹼製備成固體分散劑型以改善吳茱萸鹼的水溶解度並將吳茱萸鹼固體分散劑型製備成腸溶膜衣錠劑以防止吳茱萸鹼於酸性環境下降解。製備固體分散劑型的方式為溶劑揮發法，製備固體分散劑型的載體是聚乙烯?m咯烷酮 K15 (PVP K15)，利用體外溶離度試驗評估固體分散劑型並擇出最佳配方，最佳配方中吳茱萸鹼與載體 PVP K15 以 1:9 (w/w) 的比例混合，此配方也會進行示差掃描熱分析、傅立葉轉換紅外光譜分析以及體外飽和溶解度等物化性質試驗。接著將固體分散劑型製備成錠劑並包覆上一層主成分聚甲基丙烯酸酯的腸溶膜衣，錠劑重量為 450 ± 4.5 毫克而腸溶膜衣重量為 45 毫克，包覆完成的腸溶膜衣錠劑會以美國藥典 (USP) 的規範測試效能。吳茱萸鹼固體分散劑型最佳配方可將吳茱萸鹼的溶離效率從 0.7 提升至 61.9%，提升 88.4 倍；飽和溶解度可從 0.09 ± 0.004 提升至 2.16 ± 0.53 μg/mL，提升 24.0 倍。本研究結果證實吳茱萸鹼固體分散劑型可有效改善吳茱萸鹼的水溶解度並且腸溶膜衣錠劑可以有效防止吳茱萸鹼於酸性環境下降解。

關鍵字

吳茱萸鹼 ； 固體分散劑型 ； 溶劑揮發法 ； 酸性安定性

並列摘要

The purpose of this study was to improve the solubility and acid stability of evodiamine. Prepared an evodiamine-loaded solid dispersion to enhance the solubility of evodiamine and the prepared formulation would be made into tablets with enteric coating to protect evodiamine from cracking in the acid condition. The method to prepare solid dispersion was solvent evaporation method. The carrier of solid dispersion was polyvinylpyrrolidone K15 (PVP K15). In vitro dissolution study was used to evaluate solid dispersion formulations and find out the best one. The composition of the best solid dispersion formulation was evodiamine and PVP K15 at the ratio of 1:9 (w/w). The best formulation was also carried out with physical studies such as differential scanning calorimeter, Fourier transform infrared spectrometer and in vitro solubility study. After that, the best formulation would be made into tablets with enteric coating with ingredient, polymethacrylates. The weight of tablet was 450 ± 4.5 mg and the weight of enteric coating was 45 mg. The coated tablets were evaluated by the rule of United States Pharmacopeia (USP). The best evodiamine-loaded solid dispersion formulation could enhance the dissolution efficiency of evodiamine from 0.7 to 61.9%, about 88.4-fold, and enhance the saturated solubility of evodiamine from 0.09 ± 0.004 to 2.16 ± 0.53 μg/mL, about 24.0-fold. The result of this study confirm that the evodiamine-loaded solid dispersion formulation can improve the solubility of evodiamine and the enteric coating tablets of evodiamine-loaded solid dispersion formulation can effectively protect evodiamine from cracking in acid condition.

並列關鍵字

evodiamine ； solid dispersion ； solvent evaporation method ； acid stability

參考文獻

1. 李燕，趙燕宜，于海平，宋紅麗, 中華人民共和國藥典. 2010. 1: p. 160.

2. Zhao, N., et al., Quinolone and indole alkaloids from the fruits of Euodia rutaecarpa and their cytotoxicity against two human cancer cell lines. Phytochemistry, 2015. 109: p. 133-139.

3. Yamamoto, M., et al., Euodionosides A-G: Megastigmane glucosides from leaves of euodia meliaefolia. Phytochemistry, 2008. 69(7): p. 1586-1596.

4. Zhao, Z.Y., et al., Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-kappa B pathway. International Immunopharmacology, 2015. 28(1): p. 588-595.

5. Gavaraskar, K., et al., Therapeutic and cosmetic applications of Evodiamine and its derivatives-A patent review. Fitoterapia, 2015. 106: p. 22-35.