Preformulation report

Preformulation Report, Part I Physicochemical Properties and Analytical Testing for Drugs... 

This level of preformulation should be initiated in the beginning of the development cycle. The data consist of physicochemical properties of the chemical substance and analytical properties useful in the development of analytical methods, the evaluation of material quality, and testing for the acceptance of the formulation developed. In the early stage of development, the synthetic scheme is developed and the material available for preformulation may be limited. Thus the lack of supply quantities may affect the quality of data obtained. As the development cycle is pushed forward and the drug availability improves, data should be updated or refined with the use of more complicated and accurate methods. Part 1 of the preformulation report may be published before the establishment of specifications. The portion of this report consisting of analytical data may be known as an analytical profile in some organizations. 

Preformulation Report, Part 2 Data Supporting the Development of Dosage Forms... 

Preformulation Report, Part 3 Support for Quality Control and Finished Product Manufacturing... 

Previously published preformulation data, with the addition of updates with advanced techniques, are included in part 3. Revised pharmaceutical data as well as specifications, analytical methods of the interim developed product, and issues regarding difficulty of QA/QC may be included. Part 3 of the preformulation report must be published before the marketed product is finalized in Biobatch, a scale-up production of 10% of a manufacturing lot. 

The contents and definition of preformulation studies included are generally broader than those found in published articles or conventional textbooks. The intent is to include articles to assist the formulator in developing an optimal and ideal dosage form either for marketing or for subsequent reformulation. Thus, the following considerations should be included in a comprehensive preformulation report. 

The data for structure elucidation should be included in the preformulation reports, and the interpretation and conclusions may be reported in the same manner as those published in the Analytical Profiles of Drug Substance and Excipients. 

A collection of models for preformulation reports is suggested. These examples should by no means be considered the standards for everyone. The experience, resource limitation, time demand in delivery, personal preference, and regulatory influence may affect the contents of the report. As discussed, the items in the preformulation are somewhat extensive a shorter version of the report may be suitable for some companies. 

Depending on the structure of the organization, the contents of the preformulation report may be included in several different reports. Typically, the analytical profile may be issued by the analytical development group, and specifications of the drug substance may be issued by the QC laboratory. Physicochemical property determination, stability, compactibility, and pharmaceutical properties may be reported by the basic pharmaceutics or physical pharmacy group. The biopharmaceutical group may issue the report with KADME and bioavailability data. 

The cycle of pharmaceutical development with stages and milestones such as discovery, IND, NDA, and market introduction is discussed in this chapter. The discussion also demonstrates the fit of the preformulation into the total development activities. The contents of the preformulation reports illustrated are comprehensive in comparison with the conventional definition in preformulation. Although basic pharmaceutical principles and theory are not included in this chapter, literature references are provided. The expedience of providing documents in one volume (with three subparts) for the formulator is emphasized. 

In this chapter, pharmaceutical and health-care products, such as prescription drugs, generic drugs, OTC products, animal health products, dietary supplements (vitamins and herbal drugs), and biotechnology-derived products, are discussed in relationship to the format of preformulation reports. Topics of the preformulation study are discussed in detail. Models for some of the reports are provided in the hope that the pharmaceutical development team will devise an individual report format based on particular needs and resources. Analytical techniques useful for preformulation and regulatory conformity or requirements relative to product registration processes are also enumerated. 

Updated analytical and preformulation report of drug substance—summary of physical and chemical properties... 

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