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 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.

Preparation and in vitro/ex vivo evaluation of nanoemulsion for transnasal delivery of paliperidone

“…Zeta potential gives certain information about the surface charge properties, and further the long-term physical stability of the NEs. As all the excipient used were nonionic in nature, low zeta potential values could be attributed to the drug molecules having ionizable group (Lalani et al 2014;Patel et al 2013a, b). The zeta potential values of all formulations are reported in Table 2. PALI content of NE formulations was found in the range of 97.93-99.00 % w/w of theoretical value (5 mg/mL) ( Table 2).…”

“…Polycarbophil has been studied extensively as mucoadhesive platform for drug delivery to the nasal mucosa (Kumar et al 2009;Lalani et al 2014;Patel et al 2013a, b) in a concentration of 0.5 % w/w. This anionic polymer is most widely employed mucoadhesive polymer within pharmaceutical formulation due to its high mucoadhesive functionality and low toxicity.…”

“…Viscosity of all formulated NE formulations was very low which is shown in Table 2. Low viscosity values ensure easy handling, packing and hasslefree administration of formulations (Kumar et al 2009;Lalani et al 2014;Patel et al 2013a, b).…”

“…Polydispersity index (PDI) is a measure of globule homogeneity and it varies from 0.0 to 1.0. Polydispersity is the ratio of standard deviation to mean globule size; hence, it indicates the uniformity of globule size within the formulation (Kumar et al 2009;Lalani et al 2014;Patel et al 2013a, b). The polydispersity index was found to be between 0.129 and 0.263 for formulations PNE1-PNE10 (Table 2).…”

“…The excised superior nasal membrane was then mounted on the diffusion cell (diameter of 10 mm and mucosa thickness 0.2 ± 0.1 mm). The tissue was stabilized using phosphate buffer (pH 5) in both the compartments and allowed to stir for 15 min on a magnetic stirrer (Kumar et al 2009;Lalani et al 2014;Patel et al 2013a, b).…”