Current research aimed to fabricate and characterize lornoxicam-curcumin (LRX-CUR) co-loaded nanoemulgel (NEG) for transdermal delivery. Nanoemulgel was prepared by emulsification method using high sheared homogenization. The prepared NEG was subjected to physicochemical characterizations including thermodynamic analysis, FTIR, pH, drug content, zeta analysis (size distribution, PDI, zeta potential), rheological behavior, spreadability, in vitro drug release, and ex vivo permeation analysis. In vivo anti-inflammatory effects were assessed in experimental animals (in albino rats) using carrageenan for inducing paw edema. The NEG showed optimum and acceptable thermodynamic stability. No phase separation was observed. The pH was acceptable for use on human skin as its range was 5.5–6.5. In drug content analysis, 95.52 ± 5.63 % of LRX and 93.47 ± 8.53 % of CUR were obtained which were in official limit of USP i.e. 100 ± 10 %. No interactions and incompatibility were found between the drugs and NEG components after FTIR analysis. The viscosity and spreadability were optimum for topical application. The LRX-CUR nanoemulsion exhibited droplet size of 215.6 ± 7.89, PDI 0.219 ± 0.03 and zeta potential −12.0 ± 6.41. The LRX-CUR NEG released 85.69 ± 3.54 % of LRX and 86.89 ± 3.34 % of CUR. The permeation of LRX and CUR was 79.43 ± 5.54 % and 83.96 ± 6.21 respectively after 12 h. The optimized LRX-CUR NEG formulation significantly (p < 0.05; ANOVA) inhibited the paw edema in experimental animals as compared to the control and standard groups. Thus, LRX-CUR nanoemulgel formulation can serve as an effective substitute to the oral administration.
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