Implantable starch-based extrudates for controlled release of corticosteroids

Effective management of postoperative pain remains a major clinical challenge, driving the development of biodegradable implantable systems for localized drug delivery. Local control of postoperative inflammation plays an important role in pain management and represents a promising strategy for improving postoperative recovery. Starch-based implantable systems have recently emerged as promising biodegradable platforms for this purpose. Although polyester-based implants such as PLA and PLGA are widely used for sustained drug release, they present limitations, including poor mechanical behavior, delayed drug release, and the formation of acidic microenvironments during polymer degradation. In contrast, starch-based matrices represent an attractive alternative due to their intrinsic hydrophilicity, rapid hydration, and degradation into non-acidic products. This study aimed to characterize starch-based extrudates containing dexamethasone derivatives for potential application in postoperative pain and inflammation. Flexible cylindrical extrudates with nominal diameters of 600 μm and 1000 μm were produced using approved pharmaceutical excipients. Hydration studies revealed rapid water uptake within the first hour of incubation and swelling of approximately 30% without structural disintegration. Cyclodextrin-containing extrudates exhibited early matrix erosion within the first 24 h due to cyclodextrin dissolution, as confirmed by ¹H NMR. Low-field ¹H NMR relaxometry further revealed hydration-induced molecular reorganization within the starch matrix, with extrudates showing reduced chain mobility after incubation. Apparent solubility studies demonstrated a concentration-dependent increase in dexamethasone and dexamethasone acetate solubility in PBS in the presence of cyclodextrin. Drug release was primarily governed by extrudate diameter. Extrudates with 600 μm diameters showed faster release and reached approximately 80% cumulative release for dexamethasone and 60% for dexamethasone acetate within 10 days. Overall, starch-based extrudates enabled rapid hydration and sustained corticosteroid release for localized therapy.