Aceclofenac

Aceclofenac (ACF) is a commonly used non-steroidal anti-inflammatory drugs (NSAID) for numerous inflammatory conditions; however, its therapeutic potential is limited due to suboptimal solubility. Pharmaceutical cocrystals have demonstrated favorable and sustainable results in improving the physicochemical and biopharmaceutical characteristics of poorly soluble drugs. To enhance the solubility, dissolution rate, and bioavailability of ACF, we aimed to prepare cocrystals of this biopharmaceutics classification system (BCS) class II drug with a coformer including nicotinamide (NCT), using hot melt extrusion (HME) and liquid-assisted grinding (LAG) methods. ACF-NCT cocrystals synthesized using these methods were characterized using various methods and were further assessed for in vitro anti-osteoporotic and in vivo anti-arthritic activities. The results indicate that both LAG and HME cocrystals demonstrated significant improvement in solubility and dissolution profile compared to pure ACF. However, among these two methods, HME offered more advantages, including better solubility and dissolution profile, than the LAG method. The cocrystals achieved a remarkable 6.15-fold increase in solubility and ⁓3-fold enhancement in dissolution over pure ACF. The relative bioavailability of ACF-NCT HME cocrystal was 249.98% of pure ACF, indicating an improvement in oral bioavailability. The in vivo anti-arthritic activity also demonstrated significant improvement when compared to pure ACF. ACF-nicotinamide cocrystals prepared by hot melt extrusion achieved remarkable gains in solubility, bioavailability, and therapeutic efficacy, providing a promising strategy to overcome ACF's clinical limitations.

Chondroitin sulfate-functionalized ultra-deformable liposomes (CS-ACE-UDFLs) were developed for dual action, enhanced skin penetration and CD44-receptor-mediated precise delivery of drug. Optimization of critical parameters such as lipid concentration, sonication time, and edge activator concentration executed by Box-Behnken design. DLS particle size analyzer revealed nano-vesicle size (229.6 ± 7.95 nm), stable negative zeta potential (-41.30 ± 1.80 mV), high entrapment efficiency (73.53 ± 1.27%), and a low polydispersity index (0.253 ± 0.014) for CS-ACE-UDFLs. The encapsulation of aceclofenac confirmed through differential scanning calorimetry and X-ray diffraction studies. Surface characterization of CS-ACE-UDFLs with TEM analysis revealed a spherical morphology with a distinct chondroitin sulfate coating on the vesicle surface. In vitro release kinetics depicted the Korsmeyer-Peppas model, implying a complex release pattern, resulting from coupling of diffusion processes and matrix relaxation mechanisms. Enhanced drug release reported for CS-ACE-UDFLs (56.04% in 4 h, 91.80% in 8 h) post-incorporation edge activator compared to conventional liposomes (35.54% in 4 h, 68.51% in 8 h). The physicochemical parameters of CS-ACE-UDFLs were maintained during preliminary stability studies at 5°C. Confocal microscopy studies demonstrated a higher fluorescence intensity of functionalized ultradeformable liposomes hydrogel. Compared to ACE solution and ACE-UDFLs, CS-ACE-UDFLs showed superior anti-inflammatory activity in LPS-activated RAW 264.7 cells, characterized by enhanced cellular uptake and significantly lower levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). In vivo studies on the CFA-induced arthritis rat model exhibited a significant reduction in paw volume and arthritis score (P < 0.0001) after treatment with the CS-ACE-UDFLs hydrogel system, indicating its potential in rheumatoid arthritis therapy.