Study on Preparation and in Vitro/in Vivo Characterization of Dissolvable Microneedles Containing Inclusion Complex Loaded with Indomethacin

OBJECTIVE To prepare dissolvable microneedles containing inclusion complex loaded with indomethacin, and then investigate the transdermal properties as well as pharmacokinetic properties. METHODS The indomethacin/ hydroxypropyl-β-cyclodextrin inclusions was prepared by solution stirring and freeze drying. The preparation process was optimized by orthogonal experiment. Then the inclusion complex was loaded into the tips of microneedle by a two-step method, the piercing ability of microneedle was tested using Parafilm simulated skin, and the in vitro transdermal delivery experiment was carried out with modified Franz diffusion cells. The drug concentration in plasma was detected by HPLC, and the pharmacokinetic parameters in rats were evaluated. RESULTS The entrapment rate of the optimized prescription was 56.84%, while the drug loading was 11.90%, and the penetration rate in the third layer of Parafilm was 92%. The initial permeation rate and cumulative amount of IDM-HP-β-CD-microneedles group were higher than that of IDM-HP-b-CD solution and IDM solution. Pharmacokinetic results showed that compared with the commercially available patch, microneedles could quickly reach high drug concentration and reduce time delay. CONCLUSION The dissolvable microneedle containing inclusion complex improve the drug solubility and drug loading, and significantly improve the bioavailability of the drug. The overall results provide a potential method for the clinical application of indomethacin.