Pharmaceuticals process validation excipients

Before process validation can be started, manufacturing equipment and control instruments, as well as the formulation, must be qualified. The formulation of a pharmaceutical product should be studied in detail and qualified at the development stage, i.e., before the application for the marketing authorization is submitted. This involves preformulation studies, studies on the compatibility of active ingredients and excipients, and of final drug product and packaging material, stability studies, etc. 

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. 

The validation process of a solid dosage form begins with a validation of the raw materials, both active pharmaceutical ingredients (APIs) and excipients [16-19],... 

To the pharmaceutical world, the meaning of analytical methods validation is the process to confirm that a method does what it purports to do, that is, to document through laboratory studies that the measurement procedure can reliably assess the identity, strength, and/or quality of a bulk drug substance, excipient, or finished pharmaceutical product. To provide consistent, worldwide regulatory expectations, previously unavailable, the International Conference on Harmonization has defined the methods validation... 

Microcalorimetry has proven to be a particularly useful tool to detect different levels of disorder in pharmaceutical materials. Gao and Rytting demonstrated the validity of solution microcalorimetry to measure changes in the crystallinity during processing of both the drug compound and the excipients. Other workers have used elevated vapor pressures to trigger crystallization of disordered materials in the calorimeter and have been able to use the measured energy output to directly quantify the levels of disorder crystallinity in their samples. 

As shown in this chapter, formulating HPMC matrices can be a complex process critical factors being drug solubility, dosage level, rate-controlling polymer and excipient choice. In order to help the pharmaceutical scientists with a starting formula for hydrophilic matrix tablets, Colorcon, hic. has developed a predictive formulation service called HyperStart [97]. This system is based on mathematical models and relationships, validated with extensive experimental data. Use of the HyperStart formulation service may help to simplify the formulation and development process and reduce the time to market. 

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