Assessment of “Sameness” and/or Differences between Marketed Creams Containing Miconazole Nitrate Using a Discriminatory in vitro Release Testing (IVRT) Method

In vitro release testing (IVRT) provides an efficient method for the evaluation of drug release from semi-solid formulations. The aim of this research was to develop and validate a discriminatory IVRT system using vertical diffusion cells (VDCs) to assess generic topical products containing miconazole nitrate (MCZ). A comprehensive approach addressing all essential suitability criteria supporting the reliability of IVRT results was applied. These include mechanical validation of the VDCs, a performance verification test (PVT), validation of the analytical method (HPLC) used to quantify the drug release and validation of the IVRT method to confirm its precision, reproducibility, discriminatory ability, and robustness. Two marketed generic products were tested and assessed in accordance with the acceptance criteria for “sameness” in the FDA’s SUPAC-SS guidance which requires that the 90% confidence interval (CI) should fall within the limits of 75%–133.33%. One product was found to be in vitro equivalent to the reference product whereas the other was not. The results confirmed the suitability of the IVRT method to accurately measure the release of MCZ from topical cream products and, importantly, demonstrated the necessary discriminatory ability to assess “sameness”/differences of dermatological creams containing MCZ. Furthermore, the developed IVRT method was able to detect differences between formulations, which may be attributed to qualitative (Q1) and quantitative (Q2) properties and the microstructure and arrangement of matter (Q3).

Development of Techniques for RCP Performance Verification Test and Optimization of Flow Stability

Korea Atomic Energy Research Institute (KAERI) has designed and constructed a test facility for reactor coolant pumps (RCPs). In RCP test facility (RCPTF), it is possible to perform a type test for a newly-developed RCP as well as a production test for the Advanced Power Reactor 1400 (APR1400) RCP before its installation in nuclear power plants. The thermal hydraulic and electric capability of the RCPTF covers up to 18.5 MPa, 343 °C, 11.7 m3/s, and 14.0 MW for the design pressure, temperature, flow rate, and maximum electric power, respectively. In 2013, a commissioning test was performed to verify its designed capability, followed by several modifications in the RCPTF including signal processing and control logic to enhance the verification and evaluation capability of the RCP performance. During the commission test period, the technical activity for RCP performance verification test and optimization of flow stability have also been performed. The developed techniques can be divided into four subjects; 1) Development of flow stabilization technique for high flow condition test facility, 2) Improvement on the accuracy of performance verification factor and development of evaluation method, 3) Evaluation of test facility vibration characteristics and optimization of measurement system, and 4) RCP coast-down data production. KAERI has completed a full set of technique developments, a prerequisite for the RCP performance test.