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.

Discussion: 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.

Conclusion: Intranasal administration of TME and TNE would be effective in management of episodic and emergency pain treatment.

• Brain targeting
• intranasal
• microemulsion
• nanoemulsion
• pharmacokinetic

Acknowledgements

The authors wish to thank Dr. Anil kumar Mishra, for providing the necessary facilities to carry out the radiolabeling experiments and also thank to Ms. Krishna Chutani, for her assistance in radiolabeling experiments, Institute of Nuclear Medicine and Allied Sciences (INMAS), Ministry of Defence, New Delhi, India. The authors would like to acknowledge Council of scientific and Industrial Research (CSIR), New Delhi for providing financial support to Mr. Jigar Lalani.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.