Formulation and characterization of leflunomide/diclofenac sodium microemulsion base-gel for the transdermal treatment of inflammatory joint diseases

Purpose: This work aimed to investigate the release of poorly water-soluble drugs from microemulsion gel formulations using leflunomide and diclofenac combination as model drugs. Methods: Combination treatment, immunomodulatory (leflunomide), and NSAIDs (diclofenac sodium) were developed and tested for active rheumatoid arthritis. Various surfactants and cosurfactants have been tested for their ability to emulsify the selected oil process. Pseudo ternary diagrams have been developed to describe the field of the microemulsion. The microemulsion was prepared using isopropyl myristate as oil phase, tween 80 as a surfactant, and 1-pentanol as co-surfactant were assessed for droplet size, poly dispersibility index, zeta potential. Results: The average droplet size and zeta potential values for the selected formulation were 31.54 +/- 5.37 nm and -7.14 +/- 2.91, respectively. Optimized microemulsion systems were formulated into gel form to enhance the viscosity, carbopol was used to form a microemulsion gel evaluated for pH, spreadability, viscosity, drug content, differential scanning calorimetry, Fourier transforms infrared spectra analysis, and in vitro drug release using dialysis bag. For selected formulations, in vitro release has been studied and the F2C formula showed appropriate cumulative drug release (77.36% for leflunomide and 89.90% for diclofenac sodium) after 24 h. A 28-day anti-arthritic evaluation (body weight, paw edema, hematological parameters, and histopathology) on arthritic rat model showed significant relief of arthritis. Conclusions: Transdermal formulation containing leflunomide and diclofenac is introduced as a gel-based on microemulsion has shown promising results and can be considered a suitable formula for the ME gel capable of achieving sustained release.

Automated summary

This study aimed to investigate the release of poorly water-soluble drugs from microemulsion gel formulations using leflunomide and diclofenac as model drugs. Results showed that the selected formulation had promising droplet size and zeta potential values, indicating potential for sustained release. The optimized microemulsion gel showed appropriate drug release and significant relief of arthritis in an arthritic rat model, suggesting its suitability for sustained release applications.