Transferosomes for Trans-Nasal Brain Delivery of Clonazepam: Preparation, Optimization, Ex-Vivo Cytotoxicity and Pharmacodynamic Study
Journal: Open Access Journal of Pharmaceutical Research (Vol.1, No. 2)Publication Date: 2017-03-09
Authors : Nour SA Abdelmalak NS; Naguib MJ;
Page : 1-15
Keywords : Intranasal; Transferosomes; Clonazepam; Cytotoxicity; Pentylenetetrazole.;
Abstract
Clonazepam (CZ) is a benzodiazepine derivative that is used mainly in the treatment of status epilepticus (SE). Intranasal (IN) administration of nano-carrier systems generally have the ability to deliver the drug to the brain through olfactory and trigeminal nerves pathways circumventing the blood brain barrier (BBB). The aim of the present work was to enhance intranasal (IN) brain delivery of clonazepam in an attempt to treat status epileticus (SE). In order to achieve this goal, clonazepam transferosomes (TF) were prepared via thin film hydration technique (TFH) adopting 22 X 31 full factorial design (FFD). The twelve formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and in-vitro release. TF1 prepared using sodium deoxycholate (SDC) as edge activator (EA), lipid to edge activator molar ratio of 10:1 and 10 mg as initial drug amount showed the highest desirability value of 0.833. The optimized formula showed minor changes to sheep nasal mucosa upon ex-vivo cytotoxicity study and significant delay in the onset of pentylenetetrazole (PTZ) induced seizures. The declared results reveal the ability of the developed TF to be a strong potential candidate for the emergency treatment of SE.
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