Degradable Hydrogel Microspheres for Drug Delivery: In Vitro Performance and Influence of E-Beam Sterilization

The present work examines the in vitro drug delivery performance of degradable microspheres (DrugMic) composed of a crosslinked hydrogel of poly(ethylene glycol), with particular interest on the effect of e-beam sterilization on the stability of loaded active substances, i.e. niflumic acid (14% w/w), tadalafil (7% w/w), travoprost (0.2% w/w), buprenorphine (1.4% w/w), teicoplanin (6% w/w), and polymyxin B (5.6% w/w). Drug loading was performed on preformed microspheres degradable in 3 days, 1 or 2 weeks. Drugs were loaded onto microspheres (50-100 µm or 500-700 µm) via 1 h room-temperature incubation. After freeze-drying, drug-loaded microspheres were sterilized using e-beam irradiation (15 or 25 kGy). In vitro drug releases were done in PBS, drug elution profiles and radiostability were assessed by RP-HPLC with diode array detection. Following irradiation, DrugMic delivered niflumic acid and tadalafil for 3 days, teicoplanin and polymyxin B for 1 week, buprenorphine and travoprost for 2 weeks from microspheres degradable in 3 days, 1 and 2 weeks. Radiolysis was observed in each fraction collected during buprenorphine (0.7-20%) and travoprost (1.8-139%) release, while the HPLC profiles of polymyxin B were completely altered, indicating substantial degradation. Niflumic acid, tadalafil and teicoplanin showed no signs of radiolysis. Extemporaneous loading of buprenorphine and polymyxin B onto sterilized microspheres was attempted to avoid radiolysis. The sustained release profiles were maintained without degrading the drug. DrugMic appears to be a suitable platform for sustained drug release. The loading mode can be adapted according to the stability of the drug to irradiation.