Pain Management with Topical Aceclofenac Nanosuspension In-Vitro/In- Vivo and Proof of Concept Studies

Abstract

Introduction: Pain is one of the most common medical conditions and affects more than diabetes, heart disease, and cancer combined. Current pain treatments mainly rely on NSAIDs analgesics and remain unsatisfactory. Due to associated adverse effects such as gastrointestinal ulcers and bleeding and low solubility limits its uses. Objective: The present research focus on advance in the field of pain treatment by topical delivery of NSAIDs (aceclofenac) drugs via enhancing its solubility and diminishing related side effects. Materials and Methods: ACE-nanosuspension (ACE-NS) prepared by anti-solvent precipitation technique was characterized for particle size, PDI, zeta-potential, total drug content, DSC, FTIR, P-XRD and FESEM. Further spreadabilty, ex-vivo occlusivity, in-vitro release, ex-vivo skin permeation and retention and stability studies were performed. Dermal irritation and histopathological examinations were conducted in accordance to OECD guidelines. Proof of concept studies were accomplished using radiant tail flick and paw-licking animal model. Results: ACE-NS showed particle size of 148 ±15 nm with PDI: 0.170, zeta potential: 21.2 mV and total drug content of 86±0.23% respectively. DSC, FT-IR, P-XRD and FESEM studies revealed the thermal behavior, compatibility, solid state characterization and morphology of ACE-NS. ACE-NS loaded ointment showed a spreadability ratio of 0.23 and a drug content of 84±1.15%. In-vitro release of ACE from nano-ACE-ointment (88.07%) was higher than marketed formulation (70.55%) and free drug ointment (70.45%) after 24 hours. Release profile of nano-ACE-ointment fitted best for Higuchi model with r2 = 0.94 and n = 0.45 and its permeation flux was 9.2312 ± 0.8430 mg/cm2/h, which was significantly higher (p ≤0.05) than ACE marketed gel (2.6158 ± 0.4352 mg/cm2/h). Cutaneous irritation and histological studies revealed no inflammatory skin lesions post treatment with ACE-NS. Furthermore, ACE-NS-ointment showed better analgesic effect than marketed formulation in both radiant tail flick model (2.87 times) and paw-licking (2.73 times) animal model. Conclusion: Studies highlighted the potential of topical nano-ACE-ointment for pain management.