Development and evaluation of long-acting epidural "smart" thermoreversible injection loaded with spray-dried...

Reduction of injection frequency as well as localization of drug absorption in the injection site are important requirements in epidural pain treatment.

Our objective is to explore the production feasibility of controlled release thermoresponsive spray-dried tramadol HCl (TmH) nanospheres for localized epidural injection.

A 2⁴ factorial design was employed to study the effect of some selected variables.

F15 having the most extended release (MDT = 89.03 ± 0.76 min) was selected, based on regression analysis, for further investigation and characterization. The selected nanospheres (particle diameter = 832.5 ± 10.61 nm) with good flowing properties (θ = 28.076 ± 1.20) was reconstituted with different concentrations of Poloxamer 407 (P407) solution. The optimum reconstituted F15 nanospheres, prepared using 20% w/w P407, was liquid at room temperature, exhibited sol-gel transition at 37°C, was easily withdrawn and injected using 23G needle. The evaluation of the analgesic effect of the selected formula using hot plate method showed a desired rapid onset, yet, extended analgesic effect up to 24 h. The AUC_{0-24 h} (2998.072 ± 61.830) as well as E_max (200.788 ± 12.123) were significantly higher than drug solution and control while T_max (2.200 ± 1.095) was non-significant compared to both.

the designed formula offers a promising approach as safe depot epidural analgesic.