Comparison of Aerodynamic Particle Size Distribution Between a Next Generation Impactor and a Cascade Impactor at a Range of Flow Rates.

Wide variation in respiratory flow rates between patients emphasizes the importance of evaluating the aerodynamic particle size distribution (APSD) of dry powder inhaler (DPI) using a multi-stage impactor at different flow rates. US Pharmacopeia recently listed modified configurations of the Andersen cascade impactor (ACI) and new sets of cut-off diameter specifications for the operation at flow rates of 60 and 90 L/min. The purpose of this study was to clarify the effect of these changes on the APSD of DPI products at varied flow rates. We obtained APSD profiles of four DPIs and device combinations, Relenza®-Diskhaler® (GlaxoSmithKline Co.), Seebri®-Breezhaler® (Novartis Pharma Co.), Pulmicort®-Turbuhaler® (Astrazeneca Co.), and Spiriva®-Handihaler® (Nippon Boehringer Ingelheim Co.) using Next Generation Impactors (NGIs) and ACIs at flow rates from 28.3 to 90 L/min to evaluate the difference in the use of previous and new sets of cut-off diameter specifications. Processing the data using the new specifications for ACI apparently reduced large differences in APSD obtained by NGI and ACI with the previous specifications at low and high flow rates in all the DPIs. Selecting the appropriate configuration of ACI corresponding to the flow rate provided comparable APSD profiles of Pulmicort®-Turbuhaler® to those using NGIs at varied flow rates. The results confirmed the relevance of the current US Pharmacopeia specifications for ACI analysis in obtaining APSD profiles of DPI products at wide flow rates.

Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4).

PURPOSE: To clarify the effects of pump pulsation and flow-through cell (FTC) dissolution system settings on the hydrodynamic properties and dissolution profiles of model formulations. METHODS: Two FTC systems with different cell temperature control mechanisms were used. Particle image velocimetry (PIV) was used to analyze the hydrodynamic properties of test solutions in the flow-through dissolution test cell. Two pulsation pumps (semi-sine, full-sine) and a non-pulsatile pump were used to study the effects of varied flows on the dissolution profiles of United States Pharmacopeia standard tablets. RESULTS: PIV analysis showed periodic changes in the aligned upward fluid flow throughout the dissolution cell that was designed to reduce the temperature gradient during pump pulsation (0.5 s/pulse). The maximum instantaneous flow from the semi-sine pump was higher than that of the full-sine pump under all conditions. The flow from the semi-sine wave pump showed faster dissolution of salicylic acid and prednisone tablets than those from other pumps. The semi-sine wave pump flow showed similar dissolution profiles in the two FTC systems. CONCLUSIONS: Variations in instantaneous fluid flow caused by pump pulsation that meets the requirements of pharmacopoeias are a factor that affects the dissolution profiles of tablets in FTC systems.

Particle Image Velocimetry Evaluation of Fluid Flow Profiles in USP 4 Flow-Through Dissolution Cells.

PURPOSE: To evaluate fluid flow profiles in the flow-through cell (FTC, USP apparatus 4) system with pulsatile and non-pulsatile pumps. METHODS: Instantaneous velocity vectors in the dissolution cells were obtained from images sequentially captured by a particle image velocimetry (PIV) system. The data were sorted to follow the pump pulse cycle. RESULTS: The analysis showed changes in the flow profiles during a pump pulse (0.5 s) at a 0.025-s interval in two sizes of cells installed in the FTC system. Supplying a slow flow from the pulsatile pump induced instantaneous downward (inner layer) and upward (outer layer) flow in the larger cell during the suction phase. Analysis at varied medium and cell temperatures strongly suggested a contribution of natural convection to the complex flow caused by relatively high cell temperature. Uniform upward flow was observed in other cells and flow rate conditions. The time-averaged vertical velocities in the cells were similar in the pulsatile and non-pulsatile pump systems. CONCLUSIONS: The PIV analysis provides information on how flow rate and pump pulse affect fluid flow profiles at multiple points in flow-through dissolution cells. An appropriate temperature control should reduce the complex flow of the medium in the FTC system.