Jonker C, Hamman J H, Kotzé A F
Faculty of Health Sciences, School of Pharmacy, Department of Pharmaceutics, Potchefstroom University for Christian Higher Education, Potchefstroom 2520, South Africa.
Int J Pharm. 2002 May 15;238(1-2):205-13. doi: 10.1016/s0378-5173(02)00068-6.
Previous studies have shown that N-trimethyl chitosan chloride (TMC) is a potent absorption enhancer for hydrophilic and macromolecular compounds across mucosal surfaces. TMC proved to be effective in neutral and basic pH environments where the absorption enhancing ability of chitosan is severely hampered by its insolubility in these environments. The absorption enhancing characteristics of TMC polymers with different degrees of quaternisation were investigated in vitro and in situ to identify the most effective polymer in a neutral pH environment. Different degrees of quaternisation were obtained by varying the number and duration of the reaction steps in the synthesis process of TMC. The TMC polymers were characterised with 1H-NMR spectroscopy and the degrees of quaternisation were between 22.1 and 48.8%. Everted intestinal sacs (rats) were used to determine the effect of the polymers (0.0625-0.5% w/v) on the permeation of the hydrophilic model compound, [14C]mannitol, at a pH value of 7.4. A single pass intestinal perfusion method was also used to evaluate the permeation enhancing properties of the TMC polymers under the same conditions. The results obtained from both methods clearly showed a pronounced enhancement of [14C]mannitol permeation when administered with the different TMC polymers. It was shown that the permeation enhancing effects depend on the degree of quaternisation of TMC. In both models the best permeation enhancing results were obtained with the highest degree of quaternisation of TMC (48.8%) at a concentration of 0.5% w/v.
先前的研究表明，N-三甲基壳聚糖氯化物（TMC）是一种有效的吸收增强剂，可促进亲水性和大分子化合物跨粘膜表面的吸收。在中性和碱性pH环境中，TMC被证明是有效的，而壳聚糖在这些环境中的不溶性严重阻碍了其吸收增强能力。对具有不同季铵化程度的TMC聚合物的吸收增强特性进行了体外和原位研究，以确定在中性pH环境中最有效的聚合物。通过改变TMC合成过程中反应步骤的数量和持续时间，获得了不同程度的季铵化。用1H-NMR光谱对TMC聚合物进行了表征，季铵化程度在22.1%至48.8%之间。使用外翻肠囊（大鼠）来测定聚合物（0.0625-0.5%w/v）对亲水性模型化合物[14C]甘露醇在pH值为7.4时渗透的影响。还使用单程肠道灌注法在相同条件下评估TMC聚合物的渗透增强性能。两种方法获得的结果清楚地表明，当与不同的TMC聚合物一起给药时，[14C]甘露醇的渗透明显增强。结果表明，渗透增强作用取决于TMC的季铵化程度。在两个模型中，在浓度为0.5%w/v时，季铵化程度最高（48.8%）的TMC获得了最佳的渗透增强效果。
