The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPβCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development.

Background: Glioblastoma (GBM) harbors significant genetic heterogeneity, high infiltrative capacity, and patterns of relapse following many therapies. The expression of nuclear factor kappa-B (NF-κB p65 (RelA)) and signaling pathways is constitutively activated in GBM through inflammatory stimulation such as tumor necrosis factor-alpha (TNFα), cell invasion, motility, abnormal physiological stimuli, and inducible chemoresistance. However, the underlying anti-tumor and anti-proliferative mechanisms of NF-κB p65 (RelA) and TNFα are still poorly defined. This study aimed to investigate the expression profiling of NF-κB p65 (RelA) and TNFα as well as the effectiveness of celecoxib along with temozolomide (TMZ) in reducing the growth of the human GBM cell line SF-767. Methods: genome-wide expression profiling, enrichment analysis, immune infiltration, quantitative expression, and the Microculture Tetrazolium Test (MTT) proliferation assay were performed to appraise the effects of celecoxib and TMZ. Results: demonstrated the upregulation of NF-κB p65 (RelA) and TNFα and celecoxib reduced the viability of the human glioblastoma cell line SF-767, cell proliferation, and NF-κB p65 (RelA) and TNFα expression in a dose-dependent manner. Overall, these findings demonstrate for the first time how celecoxib therapy could mitigate the invasive characteristics of the human GBM cell line SF-767 by inhibiting the NF-κB mediated stimulation of the inflammatory cascade. Conclusion: based on current findings, we propose that celecoxib as a drug candidate in combination with temozolomide might dampen the transcriptional and enzymatic activities associated with the aggressiveness of GBM and reduce the expression of GBM-associated NF-κB p65 (RelA) and TNFα inflammatory genes expression.