Formulation development and evaluation of glucosamine hydrochloride foaming solution for transdermal delivery

Glucosamine hydrochloride (GS HCl) is an aminomonosaccharide and classified as symptoms-modifying drug in osteoarthritis. This study focused on development of glucosamine foam preparation. The effect of component of foam formulation on the permeation across the pig ear skin in vitro were elucidated using Franz-diffusion cell at 32⁰C for 24 hours and stability of GS HCl foam formulation were determined quanlitatively using validated HPLC method by pre-column derivetization with phenylisothiocyanate (PITC). The percent cumulative amount of permeated drug after 6 hours and the permeability constant (kp) up to 6 hours of various components of formulation was calculated. The potential of enhancing permeability of the surfactant studied can be ranked as the following, Desyl glucoside (cumulative amount of permeated drug 18.05%, kp = 2.20x10-6 cm/s), Caprylyl/Capryl Glucoside (cumulative amount of permeated drug 11.55%, kp = 1.46x10-6 cm/s) and Tween 80 (cumulative amount of permeated drug 10.67%, kp = 1.26x10-6 cm/s). And GS HCl foam containing desyl glucoside was the highest GS HCl permeation which more than solution (cumulative amount of permeated drug 28.05%, kp = 3.10x10-6 cm/s). The formulation with various surfactants prepared from tartrate buffer at pH 3 and sodium metabisulfite as antioxidant and storage at 5⁰C better stability than others. The presence of small quantity of ethanol in preparations could enhance the drug permeability. The results indicate that there is a possibility to develop a GS HCl transdermal dosage forms.盐酸氨基葡萄糖（Glucosamine hydrochloride, GS HCl）是一种氨基单糖，属于骨关节炎的症状修饰性药物。本研究聚焦于盐酸氨基葡萄糖泡沫制剂的开发：采用Franz扩散池（Franz-diffusion cell），于32℃条件下孵育24小时，阐明了泡沫制剂组分对离体猪耳皮肤的体外渗透行为的影响；同时采用经异硫氰酸苯酯（phenylisothiocyanate, PITC）柱前衍生化的验证型高效液相色谱法（HPLC），对GS HCl泡沫制剂的稳定性进行了定性分析。研究计算了不同制剂组分在6小时后的药物累积渗透百分率，以及前6小时的渗透常数（kp）。本研究所考察的表面活性剂的促渗透潜力可按如下顺序排序：癸基葡萄糖苷（药物累积渗透百分率18.05%，kp=2.20×10^-6 cm/s）、辛基/癸基葡萄糖苷（Caprylyl/Capryl Glucoside，药物累积渗透百分率11.55%，kp=1.46×10^-6 cm/s）及吐温80（Tween 80，药物累积渗透百分率10.67%，kp=1.26×10^-6 cm/s）。其中，添加癸基葡萄糖苷的GS HCl泡沫制剂的药物渗透效果最优，其药物累积渗透百分率高于纯溶液剂（28.05%，kp=3.10×10^-6 cm/s）。以pH 3的酒石酸盐缓冲液为溶剂、焦亚硫酸钠作为抗氧剂制备的含不同表面活性剂的制剂，于5℃储存时稳定性优于其他制剂。制剂中添加少量乙醇可进一步提升药物的渗透性能。研究结果表明，开发盐酸氨基葡萄糖经皮给药制剂具备可行性。