Development and evaluation of long-acting epidural “smart” thermoreversible injection loaded with spray-dried polymeric nanospheres using experimental design

Abstract

Context: Reduction of injection frequency as well as localization of drug absorption in the injection site are important requirements in epidural pain treatment. Purpose: Our objective is to explore the production feasibility of controlled release thermoresponsive spray-dried tramadol HCl (TmH) nanospheres for localized epidural injection. Methods: A 2⁴ factorial design was employed to study the effect of some selected variables. Results: 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prepared using 20% w/w P407, was liquid at room temperature, exhibited sol-gel transition at 37°C, was easily withdrawn and injected using 23G needle.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. Conclusion: the designed formula offers a promising approach as safe depot epidural analgesic.

Keywords::

• Epidural
• nanospheres
• thermosensitive
• depot
• analgesia