A 'biorelevant' approach to accelerated in vitro drug release testing of a biodegradable, naltrexone implant.

ABSTRACT

The development of a 'biorelevant' approach for accelerating drug release from an implant is described. A miniature, capillary system has been shown previously to be suitable for real-time release tests for a biodegradable, naltrexone implant. Whereas the real-time study under physiological condition was essential for evaluation of the system, the accelerated (short-term) method provides for a faster assessment of in vitro drug release that would be useful in product development and quality control. Increased temperature was employed as the mechanism for accelerating drug release. Release rates were investigated and compared using modifications of two devices the flow-through cell and the new, potentially more 'biorelevant' capillary device. The data generated for accelerated release using both devices through 45 days indicated approximately two-fold and four-fold increases in release rates at 45 and 55 degrees C, respectively, as compared to the real-time release rate. The similar activation energy values for both devices obtained from Arrhenius plots demonstrated that the release mechanism had been consistent; and that the rates of release could be used for long-term prediction. The rate of release reverted to that observed in real-time data, however, upon a reduction of temperature to 38 degrees C. The results demonstrated that temperature was the sole factor involved in modification of the release rate in vitro. The profiles using both systems followed zero-order kinetics after an initial period of burst release.