微量元素与健康研究

目的 探索可溶性微针的最佳复合处方及工艺，并对其可溶性微针进行载药考察和表征。方法 通过实验优化可溶性聚合物微针的最适制备工艺；选择聚乙烯醇(PVA)、羟丙基甲基纤维素(HPMC)、硫酸软骨素(CS)、聚乙烯吡咯烷酮(PVP)、羧甲基纤维素钠(CMC-Na)等常见的高分子聚合物作为基质材料，以单一或复合的方式制备空白可溶性聚合物微针。采取溶液均匀性、成膜性、含针率、机械性、气泡量、吸湿性、相容性作为评判指标筛选微针基质材料。以含针率为响应值，采用BBD-响应面法优化制备工艺，筛选出力学性能优良、不易吸湿、成型稳定的空白微针，并对最优处方制备的可溶性微针进行载药考察和表征。结果 优化得到最优空白可溶性微针的制备处方为PVP K90∶CS∶水=0.45 g∶0.50 g∶2.1 mL,优选最佳工艺为水平离心转速3 150 r/min,离心时间18 min,脱模温度38℃;每片微针载药量在8～10 mg。结论 制备的地稔可溶微针成形性、针型、力学性能较好，不易吸湿，低温下有较好的稳定性，且1 h内针尖能较好溶解。

Objective To explore the optimal composite formulation and preparation technology of soluble microneedles, as well as to investigate and characterize the drug-loading capacity of the resultant microneedles. Methods The optimal preparation technology of soluble polymeric microneedles was screened via systematic experiments. Common macromolecular polymers including polyvinyl alcohol(PVA), hydroxypropyl methylcellulose(HPMC), chondroitin sulfate(CS), polyvinylpyrrolidone(PVP), and sodium carboxymethylcellulose(CMC-Na) were adopted as matrix materials, and blank soluble polymeric microneedles were fabricated via single or composite matrix strategies. Matrix materials were screened based on evaluation indicators such as solution homogeneity, film-forming ability, needle formation rate, mechanical strength, bubble content, hygroscopicity, and compatibility. Taking the needle formation rate as the response value, the Box-Behnken design(BBD)-response surface methodology was employed to optimize the preparation process, so as to obtain blank microneedles with superior mechanical properties, low hygroscopicity, and stable molding. Furthermore, the drug-loading performance and characterization of soluble microneedles prepared with the optimal formulation were carried out. Results The optimized formulation of blank soluble microneedles was determined as PVP K90:CS:water=0.45 g: 0.50 g: 2.1 mL. The optimal preparation parameters were as follows: horizontal centrifugation speed of 3 150 r/min, centrifugation duration of 18 min, and demolding temperature of 38 ℃. The drug loading capacity of each microneedle patch ranged from 8 to 10 mg. Conclusion The prepared Melastoma dodecandrum Lour. soluble microneedles exhibit favorable formability, regular needle morphology, and excellent mechanical properties, with low hygroscopicity and good stability under low-temperature conditions. In addition, the needle tips can be rapidly and completely dissolved within 1 hour.