The USP Performance Verification Test, Part I: USP Lot P Prednisone Tablets: quality attributes and experimental variables contributing to dissolution variance.

PURPOSE: Beyond instrumental qualification, proficiency testing is not usually a prerequisite for many analytical procedures, given reliance on a manufacturer's assay validation coupled with regulatory review and inspection. Given the special features of the dissolution procedure, proficiency testing was put in place initially by pharmaceutical manufacturers and carried on by USP. Proficiency testing is designed to help ensure that execution of a dissolution procedure for solid oral dosage forms adequately supports administrative and legal decisions so that measurements made at different times, by different analysts, or with different methods can be confidently compared. USP has applied metrological principles to aid practitioners in carrying out the dissolution procedure alone and in collaborative studies to facilitate understanding potential sources of variability. MATERIALS AND METHODS: The present study aimed to identify key dissolution variables associated with USP Lot P Prednisone Tablets in conjunction with the USP Performance Verification Test (PVT). Using five dissolution test assemblies from different manufacturers, at least four of six analysts determined percents prednisone dissolved on dissolution Apparatus 1 (basket) and Apparatus 2 (paddle) on each assembly. Six replicate experiments were performed on each analyst-assembly combination with a set of six to eight tablets in each experiment. RESULTS AND CONCLUSIONS: Statistical analysis demonstrated that dissolution test assemblies were the largest factor contributing to dissolution variability. Inherent tablet variability was low, and USP Lot P Prednisone Tablets did not contribute importantly to dissolution variability. Contributions from analyst and analytical procedure also were estimated to be low.

The analysis and prediction of functional robustness of inhaler devices.

The studies described in this paper were undertaken to develop a method for the quick analysis and prediction of robustness of inhaler devices, and to define a standard among inhaler devices against which the structural integrity of new innovations could be judged. In addition, an effort was made to correlate mechanical properties with product performance metrics. The effect of mechanical stresses, alone and in combination with elevated temperatures, on the in vitro performance of pressurized metered dose inhalers (pMDIs) was investigated. The innovator pMDI devices (Ventolin HFA, GlaxoSmithKline) tested proved to be functionally robust in response to extreme mechanical stresses, suggesting that they are appropriate standards on which acceptance criteria for new devices should be defined. The actuator seat where the valve stem is inserted was identified as the critical area of the pMDI. A comparison of innovator vs. generic albuterol MDIs revealed that generic products approved as "equivalent " to the innovator products by current standards are not necessarily equivalent in ruggedness. Finite-element models of the actuator seat of Ventolin HFA (polypropylene) and QVAR 40 (high-density polyethylene) (3M Healthcare Ltd.) capable of predicting mechanical failure of MDIs were established. The material properties as well as the actuator design influenced the operational limit of MDIs. Stress analysis using finite-element modeling could be effectively used for the selection of the optimal design and appropriate materials of construction, which could lead to the development of robust inhalers while shortening the product development cycle.