McInnes Fiona J, Thapa Panna, Baillie Alan J, Welling Peter G, Watson David G, Gibson Ian, Nolan Andrea, Stevens Howard N E
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G4 0NR, UK.
Int J Pharm. 2005 Nov 4;304(1-2):72-82. doi: 10.1016/j.ijpharm.2005.07.025. Epub 2005 Sep 23.
The nasal route offers an attractive means of delivering a drug directly to the systemic circulation and avoiding hepatic first-pass metabolism, although rapid mucociliary clearance can be detrimental to nasal absorption. The in vitro and in vivo characteristics of a nasal insert formulation prepared by lyophilisation of a viscous HPMC gel solution designed to overcome this problem were studied. In vitro release of nicotine from the lyophilised insert was compared with powder and spray formulations. Stability and characterisation studies were carried out using dynamic vapour sorption, scanning electron microscopy and HPLC analysis. Nicotine formulations were administered to eight wether sheep in a randomised four-way cross-over study, and plasma nicotine assessed comparing the nasal insert formulation with conventional nasal powder, nasal spray and IV doses. In vitro release studies demonstrated prolonged nicotine release from the nasal insert formulation compared to a powder and liquid. In vivo plasma profiles appeared to show prolonged plasma nicotine levels compared to the conventional formulations, although T(max), C(max) and AUC parameters for the insert were not significantly different due to high variability in the pharmacokinetic data. In conclusion, the nasal insert displayed a promising prolonged plasma profile, which must be investigated further to provide statistical significance to prove the effect.
鼻内给药途径为将药物直接输送至体循环并避免肝脏首过代谢提供了一种有吸引力的方式，尽管快速的黏液纤毛清除可能不利于鼻腔吸收。研究了一种通过冻干粘性羟丙基甲基纤维素（HPMC）凝胶溶液制备的鼻用插入剂制剂的体外和体内特性，该制剂旨在克服这一问题。将冻干插入剂中尼古丁的体外释放与粉末和喷雾制剂进行了比较。使用动态蒸汽吸附、扫描电子显微镜和高效液相色谱分析进行了稳定性和表征研究。在一项随机四交叉研究中，将尼古丁制剂给予八只阉羊，并比较鼻用插入剂制剂与传统鼻粉、鼻喷雾剂和静脉注射剂量的血浆尼古丁水平。体外释放研究表明，与粉末和液体相比，鼻用插入剂制剂中尼古丁的释放时间延长。与传统制剂相比，体内血浆曲线似乎显示血浆尼古丁水平延长，尽管由于药代动力学数据的高变异性，插入剂的T(max)、C(max)和AUC参数没有显著差异。总之，鼻用插入剂显示出有前景的延长血浆曲线，但必须进一步研究以提供统计学意义来证明其效果。
