Patel Mrunali R, Patel Rashmin B, Bhatt Kashyap K, Patel Bharat G, Gaikwad Rajiv V
a Department of Pharmaceutics & Pharmaceutical Technology , Indukaka Ipcowala College of Pharmacy , New Vallabh Vidyanagar , Gujarat , India .
b Department of Pharmceutical Chemistry & Quality Assurance , A.R. College of Pharmacy & G.H. Patel Institute of Pharmacy , Vallabh Vidynagar , Gujarat , India .
Drug Deliv. 2016;23(1):346-54. doi: 10.3109/10717544.2014.914602. Epub 2014 May 28.
The objective of present study was to develop and evaluate paliperidone (PALI) loaded microemulsion (PALI-ME) for intranasal delivery in the treatment of schizophrenia.
The PALI-ME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine-induced compulsive behavior and spontaneous motor activity) were performed using mice. All formulations were tagged with (99m)Tc (technetium). Pharmacokinetic evaluation of PALI in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging was performed in rabbits.
PALI-ME was found stable with average droplet size of 20.01 ± 1.28 nm. In pharmacodynamic studies, significant (p < 0.05) deference in parameters estimated, were found between the treated and control groups. (99m)Tc-tagged PALI solution (PALI-SOL)/PALI-ME/PALI muco-adhesive ME (PALI-MME) was found to be stable and suitable for in vivo studies. Brain-to-blood ratio at all sampling points up to 8 h following intranasal administration of PALI-MME compared to intravenous PALI-ME was found to be 6-8 times higher signifying greater extent of distribution of the PALI in brain. Rabbit brain scintigraphy demonstrated higher intranasal uptake of the PALI into the brain.
This investigation demonstrates a prompt and larger extent of transport of PALI into the brain through intranasal PALI-MME, which may prove beneficial for treatment of schizophrenia.
本研究的目的是开发并评估用于鼻内给药治疗精神分裂症的帕利哌酮（PALI）微乳剂（PALI-ME）。
采用自发微乳化法制备PALI-ME，并对其理化参数进行表征。使用小鼠进行药效学评估（阿扑吗啡诱导的强迫行为和自发运动活动）。所有制剂均用（99m）锝标记。使用瑞士白化大鼠研究PALI在脑内的药代动力学。在兔中进行脑闪烁显像。
发现PALI-ME稳定，平均粒径为20.01±1.28nm。在药效学研究中，治疗组和对照组之间在估计参数上存在显著（p<0.05）差异。发现（99m）Tc标记的PALI溶液（PALI-SOL）/PALI-ME/PALI粘膜粘附微乳剂（PALI-MME）稳定且适用于体内研究。与静脉注射PALI-ME相比，鼻内给予PALI-MME后8小时内所有采样点的脑血比高6-8倍，表明PALI在脑中的分布程度更高。兔脑闪烁显像显示PALI经鼻向脑内的摄取更高。
本研究表明通过鼻内给予PALI-MME，PALI能迅速且大量地转运至脑内，这可能对精神分裂症的治疗有益。
