Preparation of meloxicam-salicylic acid co-crystal and its application in the treatment of rheumatoid arthritis

Meloxicam is a non-steroidal anti-inflammatory drug that can selectively inhibit cyclooxygenase 2 (COX-2), showing high anti-inflammatory activity, low gastrointestinal and renal side effects. However, the low solubility and slow dissolution rate limit its role in rapid pain relief. In this paper, using meloxicam as the active drug molecule and salicylic acid as the co-crystal former, the meloxicam-salicylic acid co-crystal (MLX-SLC CoC) was prepared by the reaction crystallization method. The co-crystal was characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The dissolution curve of the co-crystal was determined, and the result showed that the formation of drug co-crystal enhanced the solubility and dissolution rate of MLX. The oil-water partition coefficient of the MLX-SLC CoC was determined, and the results showed that the oil-water partition coefficient of the co-crystal was similar to that of pure MLX. The gel prepared by MLX-SLC CoC was used to study its in vitro release and transdermal penetration characteristics were investigated, which showed that the transdermal penetration of the drug was increased without affecting its in vitro release. Preparation of gel in the form of MLX-SLC CoC increased the drug concentration in the gel. Finally, the therapeutic effect of the gel on arthritis was preliminarily studied by establishing a rheumatoid arthritis rat model.