Validation of USP apparatus 4 method for microsphere in vitro release testing using Risperdal ® Consta ®

Abstract

The current manuscript addresses the need for a validated in vitro release testing method for controlled release parenteral microspheres. A USP apparatus 4 method was validated with the objective of possible compendial adaptation for microsphere in vitro release testing. Commercial microspheres (Risperdal ® Consta ®) were used for method validation. Accelerated and real-time release tests were conducted. The accelerated method had significantly reduced test duration and showed a good correlation with the real-time release profile (with limited number of sample analysis). Accelerated conditions were used for method validation (robustness and reproducibility). The robustness testing results revealed that release from the microspheres was not flow rate dependent and was not affected by minor variations in the method (such as cell preparation technique, amount of microspheres, flow-through cell size and size of glass beads). The significant difference in the release profile with small variations (±0.5 °C) in temperature was shown to be due to a change in risperidone catalyzed PLGA degradation in response to temperature. The accelerated method was reproducible as changing the system/equipment or the analyst did not affect the release profile. This work establishes the suitability of the modified USP apparatus 4 for possible compendial adaptation for drug release testing of microspheres.