Effect of polymer source variation on the properties and performance of risperidone microspheres.

Owing to their inherent heterogeneity, determination of similarity of poly (lactic-co-glycolic acid) (PLGA) polymers is very challenging. The complexity in controlling PLGA characteristics has been recognized as an obstacle to the development of PLGA based long-acting complex drug products (such as microspheres). The objectives of the present study were: (1) to determine minor differences in the physicochemical characteristics (such as inherent viscosity, molecular weight (Mw), monomer ratio (L/G ratio), glass transition temperature (Tg), and blockiness) as well as in the hydrolytic degradation profiles of PLGAs from different sources; and (2) to investigate the impact of PLGAs from different sources on the properties and in vitro performance of risperidone microspheres. Four PLGA polymers were purchased from different sources with similar inherent viscosity and/or Mw, L/G ratio and end groups as per the manufacturers' certificate of analysis (CoA). The physicochemical properties of these PLGAs were characterized using the same in-house methods and exhibited differences in inherent viscosity, Mw, blockiness and residue amount. Risperidone was chosen as the model drug and four microsphere formulations were prepared via the same solvent extraction/evaporation method using the PLGAs from different sources. The critical quality attributes of the microspheres (such as particle size, porosity and average pore diameter) and their in vitro release characteristics (burst effect and release rate) were shown to be different. A strong linear correlation was established between risperidone release and PLGA blockiness. This is the first time that such a correlation has been established, which promotes the potential need to further investigate the impact of PLGA blockiness on other PLGA based controlled release drug products.