Formulation, Characterization and Evaluation of Nanobubbles in Treatment of Rheumatoid Arthritis

Abstract

Methotrexate (MTX), an orange-brown, crystalline and odourless compound with a melting point of 189°C, exhibits poor water solubility but shows improved dissolution in phosphate buffer. To enhance its delivery, MTX nanobubbles were formulated using Poloxamer 407 and polyvinyl alcohol (PVA). Characterization by XRD and FTIR confirmed the crystalline structure and chemical integrity of MTX. The resulting nanobubbles were small (23–185 nm), exhibited good stability (zeta potential ranging from -18.2 to -36.1 mV), and maintained a skin-friendly pH (~6.3–6.9). The formulations demonstrated high drug entrapment efficiency (60–89%) and sustained drug release for up to 48 hours, following the Higuchi diffusion model. Among the formulations studied, F3 and F4 showed superior performance, with F4 emerging as the optimal formulation. Stability studies confirmed the nanobubbles remained stable for six months. Overall, MTX nanobubbles offer a promising platform for sustained and controlled MTX delivery with potential applications in topical and systemic therapies.