左旋多巴甲酯经鼻腔给药系统的设计与评价。

Design and evaluation of levodopa methyl ester intranasal delivery systems.

机构信息

College of Pharmacy, Dongduk Women's University, Seoul 501-759, Korea.

出版信息

J Parkinsons Dis. 2011;1(1):101-7. doi: 10.3233/JPD-2011-10011.

DOI:10.3233/JPD-2011-10011

PMID:23939261

Abstract

OBJECTIVES

This study aimed to examine the feasibility of nasal powder formulations for the delivery of levodopa (L-dopa) into the brain using highly water-soluble levodopa methyl ester hydrochloride (LDME).

METHODS

For designing nasal LDME powders, pH-rate stabilities of LDME in buffer solutions and their enzymatic degradations in rabbit nasal mucosal and serosal extracts were investigated. In vitro permeation studies were carried out with four LDME nasal powders.

RESULTS

LDME was degraded fast in weakly acidic and neutral solutions, but relatively stable in acidic solutions. In nasal extracts, LDME (50 and 200 μg/mL) was rapidly hydrolyzed, forming L-dopa, and there were no significant differences in first-order degradation rates between mucosal and serosal extracts. From the in vitro permeation studies, LDME powder formulations resulted in faster appearance rates (1.07 ± 0.39 mg/cm²/hr) of L-dopa than solution formulations (0.35 ± 0.08 mg/cm²/hr).

CONCLUSIONS

These results suggested that LDME nasal powder formulations could be useful delivery systems of L-dopa.

摘要

目的

本研究旨在考察使用高水溶性左旋多巴甲酯盐酸盐（LDME）将左旋多巴（L-dopa）递送至大脑的鼻内粉体制剂的可行性。

方法

为设计鼻内 LDME 粉末，研究了 LDME 在缓冲溶液中的 pH 速率稳定性及其在兔鼻黏膜和浆膜提取物中的酶促降解。进行了四项 LDME 鼻内粉末的体外渗透研究。

结果

LDME 在弱酸性和中性溶液中快速降解，但在酸性溶液中相对稳定。在鼻提取物中，LDME（50 和 200μg/mL）迅速水解，形成 L-dopa，并且黏膜和浆膜提取物之间的一级降解速率没有显著差异。从体外渗透研究中可以看出，LDME 粉末制剂比溶液制剂（0.35±0.08mg/cm²/hr）更快地出现 L-dopa（1.07±0.39mg/cm²/hr）。