Dexamethasone Sustained-Release Microspheres with Single-Phase Zero-Order Release Behavior for Intra-Articular Injection: Effects of Polymer Blending and Release Promoter Incorporation

Abstract Intra-articular dexamethasone injection is an effective treatment for osteoarthritis. However, the drug has a short residence time in the joint cavity, necessitating frequent administration, which results in poor patient compliance and limits its clinical use. To address these problems, dexamethasone sustained-release microspheres (Dex-MS-2) with single-phase zero-order release behavior were prepared using polymer blending combined with a release promoter. Their characteristics, in vitro release, and in vivo pharmacodynamics were evaluated. Dex-MS-2 had a slightly larger mean particle size than Dex-MS-1, but exhibited a narrower particle size distribution and good encapsulation efficiency. Compared with microspheres prepared by polymer blending alone (Dex-MS-1), the microspheres containing the release promoter exhibited no release lag and achieved zero-order release for 28 days. Following intra-articular injection in rats, Dex-MS-2 exhibited favorable anti-inflammatory activity and effectively inhibited joint swelling, with superior therapeutic efficacy to Dex-MS-1 and comparable efficacy to the marketed injection. The Dex-MS-2 developed in this study reduced the frequency of administration, improved patient compliance, and achieved sustained drug release. This formulation may effectively overcome the limitations associated with the marketed formulation.