Dissolution testing unique

Once the appropriate dissolution conditions have been established, the method should be validated for linearity, accuracy, precision, specificity, and robustness/ruggedness. This section will discuss these parameters only in relation to issues unique to dissolution testing. All dissolution testing must be performed on a calibrated dissolution apparatus meeting the mechanical and system suitability standards specified in the appropriate compendia. 

The validation requirements are discussed as they apply to both the sample preparation and sample analysis aspects of a dissolution method. The focus of the discussion in this chapter is on the validation considerations that are unique to a dissolution method. Validation is the assessment of the performance of a defined test method. The result of any successful validation exercise is a comprehensive set of data that will support the suitability of the test method for its intended use. To this end, execution of a validation exercise without a clearly defined plan can lead to many difficulties, including an incomplete or flawed set of validation data. Planning for the validation exercise must include the following determination of what performance characteristics to assess (i.e., strategy), how to assess each characteristic (i.e., experimental), and what minimum standard of performance is expected (i.e., criteria). The preparation of a validation protocol is highly recommended to clearly define the experiments and associated criteria. Validation of a test method must include experiments to assess both the sample preparation (i.e., sample dissolution) and the sample analysis. ICH Q2A [1] provides guidance for the validation characteristics of the dissolution test and is summarized in Table 4.1. 

Effect of Non-USP Adaptation. The development and validation of the dissolution test for new formulations will often probe into the use of nonpharmacopoeia adaptations (e.g., peak vessel and unique sinker configurations). The suitability of these adaptations must be assessed during method development or validation. 

As mentioned earlier in the chapter, validation of the analytical component of the dissolution test will follow guidelines similar to those described in Chapter 2, where the validation parameters are discussed in detail. For the purposes of this chapter, only an overview is provided, with emphasis on the unique requirements of the dissolution test. 

A comprehensive survey has been conducted to catalogue every workplace actinide aerosol species encountered at AWE. Each location has been listed together with details of the actinides present, their chemical and physical form, the processes undertaken, the frequency of use and legacy issues. It is apparent that the solubility characteristics of many species had been studied at AWE or other establishments, but there were some unique species for which solubility information was lacking, such as actinide alloys. These will be considered for follow on dissolution tests. 

Demonstrating equivalence of the two approaches does not infer that one is right and the other wrong. One of the unique attributes of dissolution analysis is that there is no right or wrong approach as long as tests can be validated. It is a relative method that is a function of the apparatus and... 

The selectivity of the method is given first by the ability to stay dissolved in a solution containing tartrate, second by the color of the sulfide precipitate, and finally by the fact that the sulfide salt dissolves in sodium hydroxide. The first property distinguishes it from bismuth(III) and the other cations forming insoluble oxides in neutral or alkaline solutions. But since the test does not show that a precipitate is formed in pure water, which dissolves when tartrate is added, all water-soluble cations are not excluded. So it should be viewed as a trick to facilitate dissolution only and not a part of the identification. The color of the sulfide precipitate is unique, and it is the most important criterion for a positive identification if there is any doubt when judging the result, preparing a positive control would be constructive. The solubility of the sulfide salt in sodium hydroxide is a characteristic shared with, for example, the sulfide salt of arsenate, and in classic inorganic separation the sulfide precipitate solubility in hydrochloric acid or polysulfide is used instead. " ... 

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