Typically if a sinker is needed in a dissolution test the procedure will mention the fact. Where the use of a sinker is not specifically mentioned in the procedure, it is safest to assume that the use of sinkers would represent an alternative procedure (see General Notices, Section 6.30 Alternative and Harmonized Methods and Procedures).
<1092> mentions peak vessels as noncompendial apparatus that may have some utility with proper justification.
Where dissolved air affects the dissolution of the sample, it should be removed to a level that acceptably reduces the effect. The question assumes that a deaeration method and level of dissolved air has been found to be acceptable and for some reason, an alternative is sought. Two attributes of the medium, dissolved oxygen and total dissolved gas, can be used to quantitatively compare the dissolved air content by the two methods. The effect on the dissolution of the sample by the medium deaerated by the alternative method can be used to justify its use. Statistical methods such as Analysis of Variance can be used to evaluate the resulting data sets and determine if significant differences exist.
a. Deaeration procedure
b. Mechanical calibration
c. Mechanical calibration specifications
d. Sampling procedure
The protocol relies in large part on the information available in the USP Dissolution Toolkit. The Dissolution Toolkit describes techniques enhanced beyond those in <711> to control the operation and configuration of the test assemblies. The assumption in imposing these enhanced requirements is that the data will not suffer thereby. Download the Toolkit here.
The USP Dissolution Toolkit contains enhanced mechanical calibration information. Agreement exists that additional controls can be imposed by tightening the mechanically measured attributes of Apparatus 1 and 2, insufficient data exists to determine the appropriate degree of change or that such tightening would necessarily improve the quality of the dissolution results obtained. Because the chapter is harmonized, any change to the description of Apparatus 1 or 2 would have to be agreed by the Pharmacopeial Discussion Group comprised of the European Pharmacopoeia, the Japanese Pharmacopoeia and USP.
<1092> mentions the mini-paddle as a noncompendial apparatus that may have some utility with proper justification.
<1092> mentions that basket mesh size other than 40 can be useful when the need is clearly documented by supporting data.
The basket apparatus forces the immersion of a floating dosage form and encourages surface interaction between the dosage form and the medium. However, on occasion the dosage form can attach itself to a bubble of air that is also trapped in the basket. The contact surface between the bubble and the sample will not be available for the dissolution process possibly reducing the observed dissolution rate. At some point, the bubble may detach from the sample. The attachment phenomenon and its duration may not be consistent between the sample units under test. As a source of bias, the significance can depend on the duration of this phenomenon in comparison with the total to sampling. Also, because not all sample units may experience the effect, floating due to bubble attachment can be a source of variability over the set of results. When developing a dissolution test where such phenomena may occur one approach might be to add a modifier to the medium to reduce the surface tension. For an existing dissolution procedure, observation of the occurrence of bubbles and floating units can support a retest when results fall out of specification.
The sampling zone specified in <711> is longstanding and admittedly does not describe a practical range within the vessel. The consistency of results when a well characterized material is tested can be used as a measure of variability not attributable to the sample.
USP is continuing to seek a product to replace the chlorpheniramine maleate extended-release tablets that were formerly used in the PVT for Apparatus 3 (reciprocating cylinder). Without a holistic measure of the performance of the test assembly, we are left with the evaluation of its conformance to the specified dimensions and operating parameter ranges, also known as mechanical calibration.