Study on the Preparation of Brucine Bilayer Polymer Soluble Microneedle and Its in vitro Transdermal Perme- ability under Different Drug Loading Modes / 中国药房

ABSTRACT

OBJECTIVE：To prepare Brucine （shorted for “Bru”）bilayer polymer soluble microneedles ，and to investigate their in vitro transdermal permeation characteristics under different drug loading modes. METHODS ：Taking the degree of difficulty of microneedle film uncovering ，array integrity ，bubble amount ，needle shape ，tip hardness and backing toughness as the indexes ， tip and backing materials were screened. The swelling method and drying method of matrix were screened using the morphology of microneedles as index. The double-layer polymer soluble microneedle was prepared by two-step method ，then it was characterized and evaluated in the safety. The in vitro transdermal permeation characteristics of tip-loaded ，backing-loaded and full-loaded Bru bilayer polymer soluble microneedles were investigated by Franz diffusion cell. The in vitro skin penetration curve was drawn ，and the cumulative permeability amount （Q）and cumulative permeability rate were calculated. RESULTS ：The optimal preparation technology of bilayer polymer soluble microneedles included chondroitin sulfate （CS）and polyvinylpyrrolidone K 30（PVP K 30） （1∶1，m/m）as tip materials ，15％ polyvinyl alcohol （PVA）as backing material ，matrix swelling in the refrigerator at 4 ℃ for 1 h，and drying at room temperature for 24 h in dryer. Prepared microneedle array was complete and had good mechanical properties，and could successfully puncture aluminum foil and rat skin. After microneedle treatment ，the skin could return to its original state within 6 h. The results of in vitro transdermal test showed that microneedle drug delivery could greatly increase the cumulative transdermal permeability amount of GNYL Bru，and the tip material could dissolve and release the drug within 10 min； the tip-loaded microneedle was basically released within 8 h，Q8h was 102.185 μg/cm2 and the cumulative permeability rate reached 94.05％ ； the drug cumulativepermeability rate of backing-loaded and full-loaded microneedlesexceeded 50％ within 8 h and exceeded 90％ within 48 h；Q48h were 840.77 and 1 156.73 μg/cm2，showing sustained-release characteristics. CONCLUSIONS ：Bru bilayer polymer soluble microneedles with hard tip and tough backing material are successfully prepared to achieve effective transdermal delivery and sustained release through full-loaded mode.