title: Brain targeted intranasal delivery of tramadol: comparative study of microemulsion and nanoemulsion.
abstract: OBJECTIVE
  The present investigation was aimed to develop and compare microemulsion and nanoemulsion for brain targeted intranasal delivery of tramadol to achieve maximum therapeutic efficacy in treatment of episodic and emergency pain.
  
  
  METHODS
  Tramadol microemulsion (TME) and tramadol nanoemulsion (TNE) were developed and evaluated for physical properties. Ex vivo diffusion and nasal toxicity of TME and TNE were assessed by using sheep nasal mucosa. Biodistribution, pharmacokinetic and pharmacodynamic studies in mice were also performed.
  
  
  RESULTS
  Globule sizes of TME and TNE were 16.69 ± 3.21 and 136.3 ± 4.3 nm, respectively. TNE was found be safe with respect to multiple dosing via nasal route. Both TME and TNE were stable during accelerated stability studies. AUC(0→24)in mice brain for TME and TNE was significantly higher as compared with tramadol solution. TME and TNE displayed significantly higher antinociceptive effect for a period of 16 h as compared with tramadol solution.
  
  
  CONCLUSIONS
  TME and TNE were delivered to brain, circumventing BBB in brisk manner, establishing immediately the minimum effective concentration required for therapeutic response. Significant enhancement in antinociceptive effect was observed after intranasal delivery of TME and TNE.
  
  
  CONCLUSIONS
  Intranasal administration of TME and TNE would be effective in management of episodic and emergency pain treatment.
authors.affiliation: a Pharmacy Department , The Maharaja Sayajirao University of Baroda , Kalabhavan, Vadodara , Gujarat , India.
authors.forename: Jigar
authors.initials: J
authors.lastname: Lalani
authors.affiliation: a Pharmacy Department , The Maharaja Sayajirao University of Baroda , Kalabhavan, Vadodara , Gujarat , India.
authors.forename: Dipesh
authors.initials: D
authors.lastname: Baradia
authors.affiliation: a Pharmacy Department , The Maharaja Sayajirao University of Baroda , Kalabhavan, Vadodara , Gujarat , India.
authors.forename: Riddhi
authors.initials: R
authors.lastname: Lalani
authors.affiliation: a Pharmacy Department , The Maharaja Sayajirao University of Baroda , Kalabhavan, Vadodara , Gujarat , India.
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
keywords: Brain targeting; intranasal; microemulsion; nanoemulsion; pharmacokinetic