Saitani Elmina-Marina, Papakyriakopoulou Paraskevi, Kikionis Stefanos, Pippa Natassa, Pispas Stergios, Valsami Georgia
Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.
Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.
AAPS J. 2025 Sep 18;27(6):143. doi: 10.1208/s12248-025-01128-4.
This study focuses on the development of lyophilized nasal powders of ropinirole hydrochloride (RH), composed of Poloxamer 407 triblock copolymer (P407), surfactant Tween 80 (Tw80) and derivatives of βCD [methyl-β-CD (MβCD) or hydroxy-propyl-β-CD (HPβCD)] for managing Parkinson's disease. The lyophilized compositions were produced by freeze-drying of the corresponding colloidal dispersions. The innovative aspect of this research lies in the integration of these diverse biomaterials to develop advanced drug delivery systems for nasal administration. The optimal lyophilized formulations were blended with spray-dried microparticles of mannitol and lecithin (MLMPs) in various ratios. The blending process resulted in powders with improved morphological characteristics, as evidenced by Scanning Electron Microscopy analysis. Nasal powders were characterized through in vitro diffusion and ex vivo permeation studies. Finally, a comparison between the nasal powders and the corresponding colloidal dispersions was held. Results showed that the lyophilized powders had a superior release profile compared to colloidal dispersions, and blending with MPMPs further enhanced this effect. Ex vivo powders' permeation across rabbit nasal mucosa was found to be more efficient compared to pure RH solution. In particular, the lyophilized formulation of (P407/Tw80/HPβCD)/RH 10:5 blended with MLMPs (25:75) achieved 54.40 ± 3.30% permeation of the loading dose and a mass balance of 98.15 ± 1.61%. This study demonstrates the potential of these formulations for effective nose-to-brain drug delivery. Ongoing in vivo pharmacokinetic studies are being conducted to assess the performance of the optimal formulations in an appropriate animal model.
本研究聚焦于由泊洛沙姆407三嵌段共聚物（P407）、表面活性剂吐温80（Tw80）和β - 环糊精衍生物[甲基 - β - 环糊精（MβCD）或羟丙基 - β - 环糊精（HPβCD）]组成的盐酸罗匹尼罗（RH）冻干鼻用粉剂的研发，用于治疗帕金森病。冻干组合物是通过对相应的胶体分散体进行冷冻干燥制备而成。本研究的创新点在于整合这些不同的生物材料，以开发用于鼻腔给药的先进药物递送系统。将最佳冻干制剂与喷雾干燥的甘露醇和卵磷脂微粒（MLMPs）按不同比例混合。混合过程产生了具有改善形态特征的粉末，扫描电子显微镜分析证明了这一点。通过体外扩散和离体渗透研究对鼻用粉剂进行了表征。最后，对鼻用粉剂和相应的胶体分散体进行了比较。结果表明，与胶体分散体相比，冻干粉末具有更优异的释放曲线，与MPMPs混合进一步增强了这种效果。发现离体粉末穿过兔鼻黏膜的渗透比纯RH溶液更有效。特别是，（P407/Tw80/HPβCD）/RH 10:5的冻干制剂与MLMPs（25:75）混合后，实现了54.40±3.30%的给药剂量渗透和98.15±1.61%的质量平衡。本研究证明了这些制剂在有效鼻脑药物递送方面的潜力。正在进行体内药代动力学研究，以评估最佳制剂在合适动物模型中的性能。
