Maximum torques during hot-melt extrusion were dependent on the inherent viscosity of PLGA, extrusion temperature, drug loading and drug properties, when keeping a constant screw rotation speed. The incorporation of ibuprofen into PLGA could reduce the maximum torque and Tg of PLGA caused by its plasticizing effect. A pulsatile drug release profile from PLGA hot-melt extruded implants was achieved, demonstrated by a lag time after an initial burst release, followed by a second burst or late

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... d release phase. The plasticizing effect of ibuprofen on PLGA led to higher water uptake, faster mass loss, and thus the fastest drug release in comparison with the other model drugs. The initial burst release from PLGA implants prepared by hot-melt extrusion increased with an increase in drug loading, decrease in inherent viscosity of PLGA and higher water solubility of the drug. The change in processing parameters, PLGA inherent viscosity, drug solubility and the presence of coating played an important role on the lag times of pulsatile release from PLGA implants. The factors generating the acceleration of PLGA degradation led to shorter lag-times, except the drug solubility. The second burst release phase was influenced by the drug solubility and acid-base properties. The release after the lag time was slowed with higher diazepam drug loading because of its low solubility. The release of a basic drug (tramadol HCl) was prolonged due to a possible ionic interaction. The replacement of phosphate buffer of pH 7.4 by Lipofundin to mimic in vivo subcutaneous tissue condition resulted in less water uptake, the deformation of the PLGA implant, and faster diazepam release during the diffusion phase due to the decrease in the Tg of PLGA, which is due to the presence of glycerol in the formulation.