A pharmaco–technical investigation of oxaprozin and gaultheria oil nanoemulgel: a combination therapy

Abstract

Worldwide, osteoarthritis is a significant cause of pain, disability, and socioeconomic losses. The disorder's epidemiology is diverse and complicated. Chondrocyte viability and function are compromised by oxidative stress, mechanical stress, and inflammatory mediators. This reprogrammes the cells to undergo hypertrophic differentiation and early “senescence” and increases their susceptibility to pro-catabolic and pro-inflammatory mediators. Given the above discussed pathophysiology of osteoarthritis, it is anticipated that the combination of oxaprozin and gaultheria oil (utilized in traditional medicine for rheumatoid arthritis) will definitely help alleviate the multifactorial disease. The objective of the research was to develop and assess a nanoemulsion gel/nanoemulgel (NEG) by combining oxaprozin, a non-steroidal anti-inflammatory drug (NSAID), and gaultheria oil using Carbopol 974 as a gelling agent. The aqueous titration method was used to create the nanoemulsion by plotting a pseudo-ternary phase diagram, and S_mix was used to draw the phase diagram. The formulation was optimized by employing the design of the experiment and incorporated into Carbopol 974 to formulate the NEG. Various properties of the developed formulation, such as the vesicular size, polydispersity index (PDI), zeta potential, morphology and thermodynamic stability, were tested. Furthermore, pH, homogeneity, spreadability, extrudability, texture, bioadhesion, stability, and skin irritation were assessed for the NEG. Additionally, in vitro and ex vivo tests were conducted for the assessment of the improved formulation. The result shows that the nanoemulsion has a vesicular size of 196.2 nm with good PDI and a zeta potential of −12.33 mV. Furthermore, the results show that the NEG had a biphasic release pattern with a percent cumulative drug release (%CDR) of 78.123 after 25 h. The optimized formulation was also found to be stable at 4 °C for up to 4 weeks. Furthermore, the NEG shows good drug penetration and sustained drug release pattern, which may facilitate the transport of oxaprozin and gaultheria oil through joint tissues, resulting in longer pain alleviation and decreased inflammation. In conclusion, the new formulation would be a good choice for topical medication delivery to improve the oil and oxaprozin combined therapeutic efficacy in the management of osteoarthritis.