Preformulation stability testing

Analytical testing (preformulation, stability, product release) is a core component of pharmaceutical operations from early R D through manufacturing of the commercial product. The original analytical methods are usually developed by the pioneer pharmaceutical firm and transferred to the provider. In some cases, the early methods are only preliminary methods and are not sufficiently robust to test the quality of downstream (clinical, commercial, and line extension) products and facility quality practices (cleaning validation). In those situations, the supplier is often asked to develop new methods, and in some cases those methods are transferred back to the client. In either scenario, the transfer of validated analytical methodology consists of the following four main tasks [52] ... 

Nyqvist H, Wadsten T. Preformulation of solid dosage forms light stability testing of polymorphs as a part of a preformulation process. Acta Pharm Technol 1986 32 130-132. 

During bulk drug stability and preformulation testing, preliminary formulations and processes are developed that are first stability tested on a shortterm, accelerated basis. Drug product intended for clinical use after IND approval must be stability... 

Finally, the last step in the preformulation development process is to test the candidate formulations that exhibited the greatest overall stability, using microcalorimetry. The true test of the procedure summarized in Figure 13.7 is to... 

Preformulation testing provides a basic dossier on the compound and plays a significant role in identifying possible problems and suitable approaches to formulation. Such dossiers already exist for the common excipients. The requirement for aqueous solubility is paramount and preformulation can identify salt forms that are appropriate for further development. Stability and solubility studies wiU indicate the feasibility of various types of formulation such as parenteral liquids and their probable shelf lives. Similar information can be garnered for solid products from the solid physical properties. By performing these studies on a series of candidate compounds, the optimum compound can be identified and further biological and chemical studies guided to provide the best results. 

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