Development and Characterization of Baricitinib Nanoemulgel with Antiarthritic Effect in Rats

Chemistry Rheumatology and Immunology Medicinal Chemistry Nanoscience Life Sciences Medicine Pharmacy Bioengineering
Baricitinib Transdermal delivery Nanoemulgel Skin permeation Antiarthritis activity

Academic Background

Rheumatoid Arthritis (RA) is a chronic autoimmune disease that primarily affects the synovial membrane of joints, leading to inflammation and erosive lesions. Approximately 0.5% to 1% of the global population is affected by this disease, particularly among the elderly, who often experience dysphagia, which limits the compliance and efficacy of oral medications. Current RA treatments mainly rely on systemic administration, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs). Among these, Janus kinase (JAK) inhibitors such as Baricitinib (Btb) have shown significant efficacy in treating moderate to severe RA. However, the oral formulation of Baricitinib faces challenges such as low bioavailability and significant food effects, which limit its clinical application.

To overcome these challenges, transdermal drug delivery systems (TDDS) are considered a promising alternative. Transdermal delivery can reduce gastrointestinal degradation, improve patient compliance, and allow for drug discontinuation when necessary. However, Baricitinib’s low transdermal permeability has prompted researchers to develop novel drug delivery systems to enhance its skin penetration. Nanoemulsions (NE) and nanoemulgels (NEG) have become a focus of research due to their ability to improve drug solubility and permeability. This study aims to develop a Baricitinib nanoemulgel by optimizing its formulation and performance, evaluating its potential application in RA treatment.

Source of the Paper

This paper was co-authored by Suhas Shivaji Siddheshwar, Arti Changdev Ghorpade, Someshwar Dattatraya Mankar, and Santosh Bhausaheb Dighe from Pravara Rural College of Pharmacy, India. The study was accepted on March 17, 2025, and published in the journal Bionanoscience with the DOI 10.1007/s12668-025-01908-4.

Research Process

1. Solubility Study of Baricitinib

Researchers first evaluated the solubility of Baricitinib in different oils and surfactants. The results showed that cinnamon oil, Tween 80, and ethanol were the best solvents for Baricitinib. The selection of these solvents laid the foundation for the subsequent preparation of nanoemulsions.

2. Ternary Phase Diagram Construction

The nanoemulsion formation region was determined using a ternary phase diagram. Researchers tested different ratios of oil phase, surfactant, and co-surfactant, ultimately identifying a 1:1 Smix ratio as the optimal formulation.

3. Fourier Transform Infrared Spectroscopy (FTIR) Analysis

To ensure there were no chemical interactions between Baricitinib and the formulation components, FTIR analysis was conducted. The results showed good compatibility between Baricitinib and the nanoemulgel components, with no chemical changes observed.

4. Optimization and Preparation of Nanoemulsion

The Box-Behnken design was used to optimize the nanoemulsion formulation, investigating the effects of oil concentration, Smix concentration, and stirring speed on particle size, polydispersity index (PDI), and zeta potential. The final optimized nanoemulsion formulation consisted of 5.109% oil phase, 24.401% Smix, and a stirring speed of 988.920 rpm.

5. Preparation and Characterization of Nanoemulgel

The optimized nanoemulsion was combined with a Carbopol 980 gel base to prepare the nanoemulgel. Researchers evaluated the effects of different Carbopol concentrations on the viscosity and spreadability of the nanoemulgel, ultimately selecting the 1% Carbopol formulation as the optimal choice.

6. In Vitro Drug Release and Transdermal Permeation Studies

The in vitro release and transdermal permeation of Baricitinib nanoemulgel were assessed using a Franz diffusion apparatus. The results showed that the nanoemulgel released 81.6% of the drug within 24 hours, with a transdermal permeation of 649.18 µg/cm², significantly higher than that of the conventional gel.

7. In Vivo Anti-Arthritic Activity Evaluation

Researchers used a Freund’s Complete Adjuvant (FCA)-induced arthritis rat model to evaluate the anti-arthritic effects of Baricitinib nanoemulgel. The results showed that the nanoemulgel significantly alleviated arthritis symptoms, including reduced paw swelling, increased pain threshold, and improved motor coordination.

8. Skin Irritation Study

Skin irritation experiments were conducted to verify the safety of Baricitinib nanoemulgel. The results showed that the nanoemulgel did not cause significant erythema or edema, indicating good skin tolerance.

Key Results

  1. Solubility and Ternary Phase Diagram: Baricitinib exhibited high solubility in cinnamon oil, Tween 80, and ethanol, with a 1:1 Smix ratio identified as the optimal formulation.
  2. FTIR Analysis: No chemical interactions were observed between Baricitinib and the nanoemulgel components, ensuring formulation stability.
  3. Nanoemulsion Optimization: The optimized nanoemulsion had a particle size of 77.12 nm, PDI of 0.225, and zeta potential of -19.5 mV, demonstrating good physical stability.
  4. Nanoemulgel Characterization: The 1% Carbopol nanoemulgel had a viscosity of 68,400 cp and spreadability of 8.7 g.cm/sec, making it suitable for transdermal delivery.
  5. In Vitro Release and Transdermal Permeation: The nanoemulgel released 81.6% of the drug within 24 hours, with significantly higher transdermal permeation compared to the conventional gel.
  6. In Vivo Anti-Arthritic Effects: The nanoemulgel significantly alleviated arthritis symptoms, demonstrating excellent therapeutic efficacy.
  7. Skin Irritation: The nanoemulgel did not cause significant skin irritation, indicating good safety.

Conclusion

This study successfully developed a Baricitinib nanoemulgel by optimizing its formulation and performance, significantly improving Baricitinib’s solubility and transdermal permeability. In vitro and in vivo experimental results demonstrated that the nanoemulgel exhibits sustained release, enhanced transdermal permeation, and significant anti-arthritic effects, without causing skin irritation. This research provides a novel drug delivery system for the transdermal treatment of rheumatoid arthritis, with significant clinical application potential.

Research Highlights

  1. Novel Drug Delivery System: The nanoemulgel combines the high permeability of nanoemulsions with the excellent application properties of gels, offering a new approach for transdermal delivery of Baricitinib.
  2. Optimized Formulation: The nanoemulsion formulation was optimized using the Box-Behnken design, ensuring physical stability and drug release performance.
  3. Significant Therapeutic Efficacy: The nanoemulgel demonstrated significant anti-arthritic effects in in vivo experiments, providing a new treatment option for RA patients.
  4. Good Safety Profile: Skin irritation experiments confirmed the nanoemulgel’s excellent skin tolerance, making it suitable for long-term use.

Research Value

This study not only provides a new solution for the transdermal delivery of Baricitinib but also serves as a reference for the development of transdermal delivery systems for other poorly soluble drugs. As a novel drug delivery system, nanoemulgel has broad application prospects, particularly in the long-term treatment of chronic diseases. Future research could further evaluate the long-term stability and clinical efficacy of this nanoemulgel to promote its practical application in healthcare.