Shear-induced variability in the United States pharmacopeia apparatus 2: Modifications to the existing system

Abstract

The hydrodynamics within the United States Pharmacopeia Apparatus 2 have been shown to be highly non-uniform with a potential to yield substantial variability in dissolution rate measurements. Through the use of readily available engineering tools, several geometric modifications to the device were evaluated in this study. Specifically, we examined the influence of impeller clearance, agitator type (radial and axial), and vessel geometry (PEAK vessel) on the fluid flow properties and their relation to measured dissolution rates. Increasing the impeller clearance was observed to exacerbate the heterogeneity in shear and would likely result in greater variability in dissolution measurements. Altering the impeller type was shown to yield changes in the hydrodynamic behavior; however, the overall properties and problems with the test remain the same. Use of the PEAK vessel was observed to reduce shear heterogeneity in the regions where tablets are most likely to visit during testing; however, higher shear rates may result in the inability to discriminate between true differences in dissolution rates.

Characterization and Simulation of Hydrodynamics in the Paddle, Basket and Flow-Through Dissolution Testing Apparatuses - A Review

“…CFD simulations have indicated increasing the clearance between the impeller and vessel base led to better mixing in the vessel overall, however, this also resulted in an increase in the size of the low velocity region in the lower hemispherical section of the vessel (34,35). In contrast, when the paddle is placed very close to the vessel base, a breaking flow is produced in this area along with a reduced or eliminated lower recirculation zone (34).…”

“…The use of a peak vessel increased dissolution from both low and high-solubility drugs (both known to be cone-forming) (37). Whereas the local variation in shear rate is reduced in the peak vessel, higher shear rates might result in a loss of discriminative ability of the dissolution test (35). However, with respect to the peak vessel being used to avoid the problem of coning, the more homogenous shear rates in the peak vessel environment are advantageous in promoting more reproducible dissolution results while avoiding artificially low or suppressed dissolution resulting from cone formation.…”

Comparison of Flow-Through Cell and Paddle Methods for Testing Vaginal Tablets Containing a Poorly Water-Soluble Drug

“…The basket and paddle methods are currently the most widely used dissolution techniques. However, both display several disadvantages, e.g., hydrodynamic disturbance or finite sink conditions [5,6].…”

“…It consists of a pump which forces the release medium upwards through a vertically positioned flow-through cell, a water bath and a reservoir filled with the release medium [8,9]. In spite of the fact that a variety of combinations and the diversity of available cell types allow the application of this apparatus for testing wide range of dosage forms, the flow-through cell method is particularly favoured for the in vitro dissolution studies of poorly water-soluble drugs and sustained release dosage forms due to its ability to maintain sink conditions during the test [5,8]. In the flow-through cell method, there are no problems with sampling and no further filtration steps are needed as the sample solution is automatically filtered upon leaving the cell [5].…”

“…In spite of the fact that a variety of combinations and the diversity of available cell types allow the application of this apparatus for testing wide range of dosage forms, the flow-through cell method is particularly favoured for the in vitro dissolution studies of poorly water-soluble drugs and sustained release dosage forms due to its ability to maintain sink conditions during the test [5,8]. In the flow-through cell method, there are no problems with sampling and no further filtration steps are needed as the sample solution is automatically filtered upon leaving the cell [5]. Although there are many reports in the literature describing the suitability of apparatus 4 as dissolution method for various dosage forms [10][11][12], no standard pharmacopeial tests on the use of this apparatus for non-modified release drugs are available [2,7,13].…”