自制无针粉末注射给药系统的家兔生物利用度及影响因素初探

Bioavailability and influncing factors of self-designed powder needleless injection system on rabbits

无针粉末注射技术是一种新型的给药技术,尤其适用于蛋白、多肽等大分子药物。本文选择荧光素钠作为模型药物,建立体内吸收评价方法并考察了自制无针粉末注射给药系统的家兔生物利用度。检测方法为高效液相-荧光法,灵敏度较高,分析时间小于3 min,在0.004 7～0.187 2μg.mL-1呈线性关系,绝对回收率大于97.6%,RSD小于3.6%。通过正交试验,本文还优选了载药喷射参数,结果表明气源压力、注射器型号、药粉粒径均对无针粉末注射的生物利用度有影响。注射器型号影响最大,C3型给药效果最好;增大气源压力和粉末粒径均可提高生物利用度,但气源压力和粒径过大对皮肤组织损伤也增大。采用C3型无针粉末注射器,气源压力为4 MPa,药物粒径为90～125μm的生物利用度为34.9%,与国外同类产品的药物导入效率(33%)相当。但是无针粉末注射主要的适用药物为蛋白质等大分子药物,成本较高,故仍需进一步改善系统的性能,提高生物利用度。

Powder needleless injection （PNI） is a novel method for administration of drugs, especially proteins and peptides. In this study, fluoresceinsodium was selected as model drug to evaluate and optimize the bioavailability of PNI on rabbits. The determination method was HPLC-FLD. The analyzing time of the method was within 3 minutes. A linear relationship of fluoresceinsodium was good between 0.004 7 and 0. 187 2 μg·mL^-1 and the recovery of the method was larger than 97.6% （RSD 〈3.6% ）. With the orthogonal experiments, the influence on PNI of several factors was compared. The model of the injector was the most important factor to enhance the bioavailability while gas pressure and drug diameter had positive correlation with both bioavailability and damage on skin. A condition of PNI, injector model C3, gas pressure of 4 MPa and drug diameter of 90 -125 μm, was carried out and the bioavailability of self-designed PNI system was 34.9% in compare of the result （33%） of foreign correspording product in some degree. However, the mainly applicable drug types of PNI are proteins and peptides which is of high cost. So the self-designed PNI system needs to be improved.