Importance of PLGA microparticle swelling for the control of prilocaine release

Abstract

It has recently been reported that system swelling is likely to control the onset of the third release phase from ketoprofen-loaded PLGA microparticles: However, yet it is unclear whether this type of release mechanism is also valid for other types of drugs. In this study, PLGA microparticles were loaded with different amounts of the free base prilocaine, keeping the microparticle size constant. The systems were characterized using GPC, DSC, SEM, X-ray powder diffraction, drug release measurements and the monitoring of single microparticle swelling. At lower drug loadings, tri-phasic release patterns were observed: An initial burst was followed by a period with an about constant release rate, which was followed by a third, again rapid release phase. Interestingly, the beginning of this final rapid drug release phase coincided with the onset of substantial microparticle swelling. GPC analysis revealed that the PLGA molecular weight was about 18–19 k Da at these “onset time points”. Thus, it seems that as soon as a critical polymer molecular weight is reached, important amounts of water penetrate into the system, leading to significantly increased polymer and drug mobility. Hence, microparticle swelling seems to cause the onset of the final release phase of different types of drugs.