Effect of physical ageing on the performance of dexamethasone loaded PLGA microspheres

The phenomenon of physical ageing or structural relaxation and its effect on the performance of dexamethasone loaded poly(lactide-co-glycolide) (PLGA) microspheres was evaluated. Microspheres were incubated at temperatures (−20 (control), 4 and 25 °C) below their glass transition temperature for 12 months. Physical ageing occurred in microspheres incubated at 25 °C due to structural relaxation of the polymer chains which occurs to achieve a lower equilibrium energy state. Significant physical ageing was not observed in microspheres incubated at 4 °C due to the lower molecular mobility of PLGA. The rate of structural relaxation (at 25 °C) was a function of free volume which decreased with time. The microspheres incubated at 25 °C for 12 months resulted in a slower release profile after day 25 when compared to the control microspheres. This was speculated to be due to a reduction in free volume upon physical ageing which in turn may reduce water absorption and retention of acidic degradation products in the PLGA matrix, hence reducing the degradation rate of PLGA. Therefore, exposure to ambient temperature during storage, shipping or handling may cause physical ageing in PLGA microspheres and hence, their performance may be affected. Storage temperatures of 4 °C or lower may be considered appropriate for PLGA microspheres.

DSC thermograms of dexamethasone loaded PLGA microspheres showed an increase in the Tg and enthalpy of relaxation with time following storage at 25 °C. There was a slight change in the in vitro release profile of the microspheres following storage at 25 °C for 12 months.Figure optionsDownload as PowerPoint slide