Development And Application Of Needle-Free Drug Powder Delivery System

Needle-Free Drug Powder Delivery System(NFDPDS), a novel drug delivery system developed rapidly worldwide, represents attractive advantage in effective, needle-free and painless delivery of drugs, used a supersonic air flow to energize drug powders to such a high speed that they can penetrate the stratum corneum into dermis or mucosa membrane For the advantage, NFDPDS befits those applications of drug delivery to children,needle-feared or self-administering patients, and of health care in grave and unexpected accidents, or in remote area and largescale battle field.In this paper, the device of NFDPDS and the proper powder form of drug were investigated respectively and combinatively to assembly and establish the homemade technique platform of NFDPDS. The main results are summarized below:1. The NFDPDS injector was optimized in nozzle, gas holder and other key components to achieve better performance of portability, stability and safety compared to the prototypal one developed in our former study. After optimization, the type-A nozzle was developed using nitrogen as gas power in pressure of 4MPa and the inject-volume was 5-10 ml per delivery,2. Six powder models to load drug were prepared, . The key characteristics of these powders in diameter, distribution and density were determined through light microscope , LS800 lasersizer and other measurements. In comparison the characteristics of these powders, the powder prepared with both polymer and metal salt showed attractive advantage and the proportioning was optimized to achieve the density of powder within 1.0 to 3.0g/mL.3. With in vitro and in vivo evaluation, the self-made NFDPDS was demonstrated to be effective, safe and applicable.(1) The penetration depth of NFDPDS was investigated in vitro with human skin, pigskin and gelatin gel as injection target. The results showed that the maximum penetration depth can increase synchronously with powder size and density increasing.The max penetration depth can be predicted regularly.(2) Fluoresceinsodium was selected as model drug to evaluate the human skin absorption rate in vitro delivered by NFDPDS.The results showed that the delivery rate of NFDPDS could reach 30-40% under optimized condition, which was 400 times higher than those of the conventional transdermic preparations.(3) The bioavailability delivered by NFDPDS was also investigated on rabbit with fluoresceinsodium as model drug. The results showed that the bioavailability of NFDPDS could reach 20-40% under different gas pressure.(4) The evaluation of skin stimulation showed that the type-A NFDPDS was rather safe under gas pressure of 4MPa.4. The NFDPDS preparation of tetanus toxoid (TT) was primarily developed in this paper using aluminum hydroxide as complement based on the optimized conditions above to achieve the proper diameter of drug powder in 60.55±4.44μm. The immuno-effect of TT- NFDPDS was evaluated in delivery to mice. The result showed that the TT- NFDPDS could achieve an equivalent immuno-effect to normal TT preparation.5.In the second example,insulin needle-free powder injection is prepared which key characters is investigated. Metabolism and effect of insulin is studied with rabbit in vivo. Effect bioavailability of insulin of rabbit is 34.2%, relatively bioavailability is 30.9%. It can be found that insulin needle-free powder injection lower blood suger slowlier, blandlier, acting more long, and without phenomenon of blood suger too low.