Fabrication of Spanlastics as a potential transdermal delivery of lornoxicam for efficient management of osteoarthritis and side effect mitigation: Formula optimization, in vitro characterization, ex vivo, and in vivo assessments.

Lornoxicam (LRX) is a strong non-steroidal anti-inflammatory drug used for managing osteoarthritis (OA). LRX has low oral bioavailability because of its low water solubility and extensive first-pass effect. This study aimed to develop spanlastics (SPs) for sustained transdermal delivery of LRX to enhance its solubility, permeability, anti-osteoarthritic efficacy, and minimize its oral side effects. LRX-SPs were prepared using the ethanol injection method based on a D-optimal design. The optimized SP formula (F4) consisted of LRX (10 mg), Kolliphor RH40 (200 mg), Span 60 (500 mg), and oleic acid (200 mg). It showed the least particle size (137.8 ± 6.93 nm), polydispersity index (0.23 ± 0.02), and the highest entrapment efficiency% (88.7 ± 4.01%), zeta potential (-34.6 ± 3.58 mV). F4 enhanced LRX release and ex vivo permeation by 1.69- and 2.04-fold compared to LRX suspension, respectively. Then F4 was converted to gel by adding 1% Carbopol, which boosted LRX release and ex vivo permeation by 1.52- and 1.78-fold, respectively, compared with free LRX gel. In vivo evaluation of anti-inflammatory activity of SP gel by MIA-induced OA in rats has verified significant inhibition of knee joint edema, oxidative stress/inflammatory cascades, as compared with free LRX gel and market tablet. Besides, the SP gel has reverted MIA-induced alteration of joint degradation/regeneration and apoptotic markers. These findings were mirrored in animals' motor performance tests and histopathological investigations, confirming the SP gel's efficacy in reducing OA deterioration without halting gastroprotective prostaglandin E2 levels. Therefore, it could be considered a promising approach for transdermal delivery of LRX for managing OA.