Title:Pain Management with Topical Aceclofenac Nanosuspension In-Vitro/In-
Vivo and Proof of Concept Studies
Volume: 17
Issue: 4
Author(s): Shaina Nagpal, Parina Kumari, Komal Saini and Vandita Kakkar*
Affiliation:
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India
Keywords:
Nanosuspension, pain, aceclofenac, histopathology, dermal irritation, analgesic studies, in vitro, in vivo.
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 NSAID analgesics
and remain unsatisfactory. Due to associated adverse effects such as gastrointestinal ulcers and
bleeding, low solubility limits its use.
Objective: The present research focuses on advances 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. Furthermore, spreadability, 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 with OECD guidelines. Proof of concept studies was accomplished
using radiant tail-flick and paw-licking animal models.
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-NSloaded
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 the 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 a better analgesic effect than the marketed formulation
in both the 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.
