吲哚美辛包合物可溶性微针的制备及体内外特性研究

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

关键词:  吲哚美辛  包合物  可溶性微针  经皮给药

Key words:  indomethacin  inclusion complex  dissolvable microneedles  transdermal drug delivery

摘要:

目的 制备载有吲哚美辛包合物的可溶性微针，考察其体外透皮性能并进行药动学特性研究。方法 采用溶液搅拌-冷冻干燥法制备吲哚美辛/羟丙基-β-环糊精包合物，正交试验筛选最佳制备处方。通过两步法将包合物负载于可溶性微针，用Parafilm模拟皮肤测试微针穿刺能力，以改良Franz扩散池进行体外经皮释放实验。建立HPLC测定大鼠血浆中吲哚美辛的方法，评价微针用于大鼠给药的药动学特征。结果 最佳处方制备的包合物包埋率为56.84%，载药量为11.90%；微针对第3层Parafilm的刺穿率为92%；IDM-HP-β-CD微针的初始体外经皮渗透速率和单位面积渗透量显著高于IDM-HP-b-CD溶液以及IDM饱和溶液；药动学结果显示微针与市售贴片相比能快速达到较高血药浓度，减少时滞。结论 包合物可溶性微针提高了药物溶解度和载药量，快速释放并显著提高药物的生物利用度，为吲哚美辛的临床应用开发了新的途径。

Abstract:

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.