Development and evaluation of tofacitinib transdermal system for the treatment of rheumatoid arthritis in rats.

CONTEXT

Tofacitinib tablet is approved for the treatment of rheumatoid arthritis (RA). However, tofacitinib (Tfc) faces extensive first-pass metabolism following oral administration.

AIM

To develop transdermal systems of Tfc and evaluate their efficacies against RA using Freund's Complete Adjuvant immunized arthritis rat model.

METHODS

These systems were prepared by solvent casting method and evaluated for texture, needle strength, skin penetrability, drug release, skin permeation, stability, and anti-arthritic activity.

RESULTS AND DISCUSSION

Transdermal patch (TS) showed smooth texture, good mechanical strength, slow-release, and slow permeation through the skin. Microneedle array (MNS) showed good needle strength, with required skin penetrability. MNS and TS showed 95% and 24% drug release, and 82% and 12% drug permeation, respectively in 4 h. The developed systems were found to be stable for 90 days at very stressful conditions, that is, 40 ± 2 °C and 75 ± 5% RH. MNS and TS both reduced arthritic scores (at  < 0.01 and  < 0.001 level, respectively) and the level of inflammatory cytokines (at  < 0.05 and  < 0.01 level, respectively) significantly as compared to that of the drug solution (DS). MNS and TS were found to be effective in restoring histological alterations (annum, synovial hyperplasia, synovial constriction, and cartilage and articular erosions) toward normal.

CONCLUSION

TS and MNS were found to be stable and effective for the treatment of arthritis and hence considered a good alternative for the treatment of RA with better clinical pertinence.