An Engineered Floating Nanoparticulate System to Modulate Biopharmaceutical Performance and Therapeutic Efficacy of Tapentadol in Chronic Neuropathic Pain Management

Background: Tapentadol is an effective centrally acting analgesic for treating neuropathic pain. However, its short half-life, high first-pass metabolism, and requirement for frequent dosing limit its therapeutic effect and patient compliance. The purpose of the present innovation was to develop cost-effective tapentadol-loaded floating nanoparticles (TFNs) for sustained oral delivery. Methods: TFNs were prepared using the double emulsion solvent evaporation method. The effects of various formulation and process parameters, including polymer ratio, drug concentration, surfactant concentration and type, sonication time, and external phase volume were systematically studied. Analytical physicochemical characterization, morphology, buoyancy and drug release behavior were carried out. In vivo performance was evaluated by performing pharmacokinetic, tissue distribution, and pharmacodynamics studies in a chronic constriction injury model. Results: The optimized formulation exhibited spherical shape with nano-size (320.66 ± 17.50 nm), and good entrapment efficiency (82.85 ± 6.57%). Analytical characterization confirmed successful drug encapsulation and compatibility with formulation components. The engineered floating nanoparticulate architecture allowed both long gastric drug retention and a controlled drug release, governed by an anomalous diffusion-controlled mechanism. Pharmacokinetic evaluation revealed 3.36-fold higher relative oral bioavailability from TFNs. In addition, 1.49-fold higher drug availability in brain with TFNs was observed. Pharmacodynamic studies demonstrated a marked reduction in neuropathic pain responses, confirming the superior and prolonged analgesic effect of TFNs. Conclusions: The findings establish the developed TFNs as a promising controlled-release system for effective and sustained management of neuropathic pain. Even so, further studies focusing on large-scale production, long-term safety, and clinical evaluation are necessary before the formulation can be advanced for clinical application.