Substance and Excipient Characterization

Materials from reputable companies may be supplied with detailed specifications and their methods of determination may be obtained, if requested. The information on specifications such as purity or content is very often available. Nevertheless, it is prudent to confirm such information. The information provided by different suppliers may vary. The type of tests carried out or the techniques used for the characterization of a particular physical property, for example, the particle size distribution, may be different. Comparison of materials from different suppliers can therefore be difficult. Sometimes, the analytical result supplied by the manufacturer is given as falling within a certain range and this gives virtually no information about batch to batch variation of the material. 

It is therefore important to have a system of in-house characterization of raw materials alongside the stability and functional tests for the finished product. Whenever possible, tests carried out should yield quantitative results rather than a pass/ fail or present/absent assessment. Retrospective studies of the finished product test 

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Comprehensive physicochemical characterization of any raw material is a crucial and multi-phased requirement for the selection and validation of that matter as a constituent of a product or part of the product development process (Morris et al., 1998). Such demand is especially important in the pharmaceutical industry because of the presence of several compounds assembled in a formulation, such as active substances and excipients, which highlights the importance of compatibility among them. Besides, variations in raw materials due to different sources, periods of extraction and various environmental factors may lead to failures in production and/or in the dosage form performance (Morris et al., 1998). Additionally, economic issues are also related to the need for investigating the physicochemical characteristics of raw materials since those features may determine the most adequate and low-cost material for specific procedures and dosage forms. 

D. Methodology Related to the Characterization of Drug Substances and Excipients... 

Confirm formulation composition, including, but not limited to, drug substance content, drug substance stability, excipient levels, water, and residual solvents, using appropriately characterized methods. 

Knowledge of synthetic impurities and degradation products can be derived from the historical information that has accumulated for the drug substance/prod-uct. Ideally, a library of impurity and degradation compound reference standards is synthesized and characterized and sufficient quantities are made available. These compounds or an impurity cocktail can be spiked into the pure drug substance and any excipients (placebo sample matrix) to determine if the matrix interferes with the quantitation of the compound(s) of interest by comparing to an unspiked sample and sample diluent. 

Though in competition with other analytical techniques, CE has proven its potential and necessity to be used for the characterization of small-molecule pharmaceuticals. Due to the versatility of the system, CE can be applied for the determination of physicochemical properties, identification, purity and stability analysis, and cleaning verification of the drug substance, its precursors, process chemicals, the drug product, and its excipients. 

Part II starts with the possibilities of ACE for characterizing the relevant physicochemical properties of drugs such as lipophilicity/hydrophilicity as well as thermodynamic parameters such as enthalpy of solubilization. This part also characterizes interactions between pharmaceutical excipients such as amphiphilic substances (below CMC) and cyclodextrins, which are of interest for influencing the bioavailability of drugs from pharmaceutical formulations. The same holds for interactions of drugs with pharmaceutical vehicle systems such as micelles, microemulsions, and liposomes. 

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