Methylprednisolone‐loaded PLGA microspheres: A new formulation for sustained release via intra‐articular administration. A comparison study with methylprednisolone acetate in rats

Methylprednisolone (MP) released by poly(d,l‐lactide‐co‐glycolide) microspheres (PLGA MS) was monitored in plasma after intra‐articular (i.a.) administration into rat joint. A validated LC‐ESI‐MS/MS method was used to quantify the plasmatic concentrations of MP. The calculated pharmacokinetic parameters were compared to those obtained after the i.a. administration of a commercially available suspension of MP acetate (MPA). Different pharmacokinetic profiles were observed in the two formulations, and a lower peak level (Cmax = 13.7 ± 4.3 ng·mL−1) and AUC0-72 h (198 ± 45 ng·mL−1·h) were observed for MP‐PLGA MS than MPA (Cmax = 18.4 ± 2.7 ng·mL−1) and AUC0-72 h (943 ± 249 ng·mL−1·h). The administration of MP‐PLGA MS resulted in a rapid increase in the MP concentration at 30 min, with a tmax at 0.8 ± 0.3 h. Instead, for the MPA suspension the tmax was 32.0 ± 13.9 h. These differences were indirectly confirmed by the evaluation of the extra‐articular effects, namely, carrageenan‐induced paw edema, since MP‐PLGA MS showed a lower anti‐inflammatory activity than MPA. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4580-4586, 2011