PLGA implants for controlled drug release: Impact of the diameter

The aim of this study was to better understand the importance of the diameter of poly(lactic-co-glycolic acid) (PLGA)-based implants on system performance, in particular the control of drug release. Different types of ibuprofen-loaded implants were prepared by hot melt extrusion using a Leistritz Nano 16 twin-screw extruder. Drug release was measured in well agitated phosphate buffer pH7.4 bulk fluid and in agarose gels in Eppendorf tubes or transwell plates. Dynamic changes in the implants' dry & wet mass, volume, polymer molecular weight as well as inner & outer morphology were monitored using gravimetric analysis, optical macroscopy, gel permeation chromatography and scanning electron microscopy. The physical states of the drug and polymer were determined by DSC. Also pH changes in the release medium were investigated. Irrespective of the type of experimental set-up, the resulting absolute and relative drug release rates decreased with increasing implant diameter (0.7-2.8 mm). Bi-phasic drug release was observed in all cases from the monolithic solutions (ibuprofen was dissolved in the polymer): A zero order release phase was followed by a final, rapid drug release phase (accounting for 80-90% of the total drug dose). The decrease in the relative drug release rate with increasing system diameter can be explained by the increase in the diffusion pathway lengths to be overcome. Interestingly, also the onset of the final rapid drug release phase was delayed with increasing implant diameter. This can probably be attributed to the higher mechanical stability of thicker devices, offering more resistance to substantial entire system swelling.