红景天苷喷雾成膜剂递送系统的构建及跨尺度皮肤渗透模拟研究

Construction of a Delivery System for Salidroside spray film former and Multiscale Skin Permeation Simulation Study

关键词:  跨尺度  经皮渗透  皮肤模型  喷雾成膜剂  应力性骨折  红景天苷

Key words:  Multi-scale  Transdermal permeation  Skin model  Spray film former  Stress fracture  Salidroside

摘要:

目的：本研究旨在开发一种红景天苷喷雾成膜剂，以用于应力性骨折的治疗。方法：以红景天苷为模型药物，通过单因素实验结合中心复合设计-响应面法（CCD-RSM）优化确定处方组成，并对制备的红景天苷喷雾成膜剂进行质量评价、制剂表征与体外释放研究；构建皮肤物理模型，结合有限元法模拟药物的体外扩散过程。结果：所制备的红景天苷喷雾成膜剂的最佳处方组成为：PVA 1.42 g、PVP-K30 0.47 g、HPMC 0.1 g、甘油4 mL、无水乙醇24.2 mL、适量药物，最终用纯水定容至100 mL。所得制剂外观透明澄清，pH值介于5.11–5.13之间，与人体皮肤平均pH相近；显微结构观察显示膜剂无气泡、无颗粒，均匀性良好。在紫外和红外光谱下分别扫描吸光度和透过率，结果显示加药制剂与空白制剂基本相同，表明相容性良好且药物分散均匀。体外透皮渗透实验显示该制剂具备良好的缓释特性；进一步的皮肤扩散模拟结果表明，药物可随时间逐步由角质层渗透至表皮层，并最终扩散至真皮层内。结论：红景天苷喷雾成膜剂制备工艺简便可行，药物与制剂融合良好，能适应人体皮肤pH。

Abstract:

OBJECTIVE This study aims to develop a spray film former containing Salidroside for the treatment of stress fractures. METHODS Using salidroside as the model drug, the formulation composition was optimised through single-factor experiments combined with a central composite design-response surface methodology (CCD-RSM). The prepared salidroside spray film former underwent quality evaluation, formulation characterisation, and in vitro release studies. A skin physical model was constructed, and the in vitro diffusion process of the drug was simulated using finite element analysis. RESULTS The optimal formulation for the prepared Salidroside spray film former comprises: PVA 1.42 g, PVP-K30 0.47 g, HPMC 0.1 g, glycerol 4 mL, anhydrous ethanol 24.2 mL, and an appropriate amount of drug, with the final volume adjusted to 100 mL using purified water. The resulting formulation appeared transparent and clear, with a pH ranging between 5.11 and 5.13, approximating the average pH of human skin. Microscopic examination revealed a film devoid of bubbles or particles, exhibiting excellent uniformity. Scanning of absorbance and transmittance under ultraviolet and infrared spectroscopy showed the drug-containing formulation to be essentially identical to the blank formulation, indicating good compatibility and uniform drug dispersion. In vitro transdermal permeation studies demonstrated the formulation possesses favourable sustained-release properties. Further skin diffusion simulation results indicated the drug gradually permeates from the stratum corneum into the epidermis over time, ultimately diffusing into the dermis. CONCLUSION The preparation process of Salidroside spray film former is simple and feasible, with good drug-formulation compatibility and adaptability to human skin pH.