Sustained - release microspheric gel of meloxicam: Preparation, evaluation in vitro and in vivo

Osteoarthritis (OA) is the common form of chronic joint disease. The disease progression can affect all joints of the body, seriously affecting patients’ quality of life. The most effective clinical treatment for OA at the moment is the oral or intravenous administration of non-steroidal anti-inflammatory drugs, such as meloxicam (MX). However, certain challenges associated with the conventional use of those drugs include long dosing cycles, poor patient compliance, and systemic toxic side effects, primarily gastrointestinal reactions. Joint synovial fluid mainly consists of sodium hyaluronate (HA). In recent years, HA has been developed and used to treat OA with local injections. However, it also faces the limitations of short injection cycle, frequent administration, and increases the risk of exogenous infection. In this study, a microsphere gel formulation containing PL407, HA and meloxicam microspheres was prepared and the MX-MS-Gel system showed good performance, syringeability and stability. The results of in vitro release studies showed that the MX-MS-Gel released 8.6% in vitro at 72 h and 28.0% at 480 h, with a more moderate drug release. By injecting iodoacetic acid into the knee joint of rats to establish an OA model, MX-MS-Gel significantly improved the inflammatory response of OA, while the safety of MX-MS-Gel was superior and evaluated in this study, which was safe. The results showed that MX-MS-Gel could realize the purpose of delaying the drug release rate and reducing the frequency of administration, thus improving patient compliance and medication safety.