Hot melt extruded PLGA implants loaded with ibuprofen: How heat exposure alters the physical drug state

Hot melt extrusion offers an interesting potential for the manufacturing of poly(lactic-co-glycolic acid) (PLGA)-based implants. However, the heat treatment might substantially alter the polymer, drug and degree of drug-polymer mixing. The aim of this study was to better understand the impact of varying the exposure time to 105 °C in the case of ibuprofen-loaded PLGA implants. In vitro drug release was measured in phosphate buffer pH 7.4. Optical and scanning electron microscopy, DSC, GPC, X-ray diffraction as well as gravimetric analysis were used to monitor dynamic changes of the implants’ morphology, dry & wet mass and average polymer molecular weight. Interestingly, increasing the exposure time from 3 to 15 min led to a decrease in the amount of crystalline drug present in the system, resulting in a slight decrease in the initial burst release. The average PLGA molecular weight also slightly decreased during the heat treatment. In contrast, the relatively rapid penetration of water into the implant and subsequent polymer degradation throughout the device did not seem to be affected to a noteworthy extent. Also the onset of substantial implant swelling after about 1 week and the subsequent beginning of the final rapid drug release phase (accounting for about 80% of the total drug dose) were not significantly altered. Thus, in this study, the changes in the physical state of the drug in the implant induced by prolonged heat exposure had only a limited impact on system performance. However, for different drugs and polymers, changes in their physical state as a function of the heat exposure time might have more importance consequences. Careful monitoring of these kinetic aspects is recommended to assure desired product quality