Investigation on modeling and correlating drug release profiles in the accelerated and real-time conditions to formulate leuprolide acetate-loaded biodegradable microspheres

Abstract

Leuprolide acetate (LA)-loaded microspheres containing different types of biodegradable poly(lactic-co-glycolic acid) (PLGA) were prepared by using the W/O/W double-emulsion solvent evaporation method. These formulations were characterized in terms of particle size, drug loading capacity and drug release kinetics. According to the data on modelling in vitro drug release profiles in accelerated and real-time conditions, the microspheres containing mainly PLGA (L:G = 50:50) or PLGA (L:G = 75:25) exhibited triphasic or biphasic release profiles, respectively. A good correlation was established between real-time at 37 °C and accelerated at 50 °C release data, suggesting that the accelerated release testing method could be useful for a rapid assessment of the in vitro drug release characteristics of the prepared formulations. The particle size, drug loading capacity and drug release characteristics of LA-PLGA microspheres were proved to be dependent upon PLGA types with different monomer ratios, PLGA molecular weight, and pore-forming agent. With reference to drug release characteristics, our microsphere formulation composed of PLGA 75:25 and ammonium bicarbonate (as a pore-forming agent) was most equivalent to the reference microspheres for 1-month administration.