In vitro and preclinical assessment of factorial design based nanoethosomes transgel formulation of an opioid analgesic

Abstract

Context: Tramadol is a centrally acting analgesic and requires frequent dosing. Hence, judicious selection of retarding formulations is necessary. Transdermal ethosomal gel delivery has been recognized as an alternative route to oral delivery.

Objective: The objective was to develop statistically optimized ethosomal systems for enhanced transdermal activity of tramadol vis-à-vis traditional liposomes.

Materials and methods: Box-Behnken design was employed for optimization of nanoethosomes using phospholipon 90G (A), ethanol (B), and sonication time (C) as independent variables while dependent variables were the vesicle size (Y₁), entrapment efficiency (Y₂), and flux (Y₃). It was prepared by rotary evaporation method and characterized for various parameters including entrapment efficiency, size and transflux. Preclinical assessments were conducted on Wistar rats to measure the performance of developed formulations.

Results: The optimized formulation provided mean vesicles size, reasonable entrapment efficiency and enhanced flux when compared with liposome (control). In-vivo absorption study showed a significant increase in bioavailability (7.51 times) compared with oral tramadol. The average primary irritancy index was found to be 1.4, indicating it to be non-irritant and safe for use.

Discussion and conclusion: The results also demonstrated that encapsulated tramadol increases its biological activity due to the superior skin penetration potential. The preclinical study indicates a significant (P < 0.05) extended analgesic effect compared to oral solution using the hot plate test method. The overall results suggest that developed formulation is an efficient carrier for transdermal delivery of tramadol.

Keywords:

• Box-Behnken design
• in-vivo study
• nanoethosome
• tramadol

Declaration of interest

These authors declare that they have no conflict of interest. Shakeeb Ahmed is thankful to UGC for providing Junior Research Fellowship.