Preformulation, active pharmaceutical

In a more traditional pharmaceutical setting, this characterization would be done during preformulation studies. With the availability of automation and the ability to conduct most of these experiments with small quantities of material, more preformulation activities are being shifted earlier into drug discovery. Recently, Balbach and Korn37 reported a "100 mg approach" to pharmaceutical evaluation of early development compounds. Additional absorption, metabolism, distribution, elimination, and toxicity38 screens may also be conducted at this stage. 

Preformulation profde or characterization of the components of the formula, which includes all the basic physical or chemical information about the active pharmaceutical ingredients (API, or the chemical entity) and excipients... 

By the time an active pharmaceutical ingredient (API) is made available to an analytical chemist in the formulation development group, most or all of the physical characteristics of an API has already been studied and the information should be available in some sort of a report from the drug substance group or preformulation group. Some of the key parameters that an analytical chemist in formulation development requires from such a report are the solubility and solution stability. 

Another potential barrier is any overlapping expertise there may be in Research and Development groups. For example, overlap may occur between Preformulation in Pharmaceutical Development and Physical Chemistry in Research, or between Biopharmaceutics in Development and Drug Metabolism in Research. In these cases, it is important to clarify and agree which group does what activity. 

In order to develop a robust formula for a drug product (pharmaceutical dosage form) it is important to understand the chemical and physical properties of the API in conjunction with excipients that may be used to create the most stable product formula in terms of activity and potency. An outline of possible preformulation studies that should be conducted to ensure a proper and complete understanding of the chemical and physical properties of the API is presented in Table 3. 

Solubility, enzyme activity, chemical and conformational stability of pharmaceutically active proteins under non-aqueous conditions have been well characterized (Zaks and Klibanov, 1988a Zaks and Klibanov 1988b Houen, 1996). Many of the solvents utilized in the literature are not pharmaceutically acceptable, and much of this work has not been directly applied to non-aqueous pharmaceutical formulations. However, the fundamental science and elucidation of concepts important to successfully utilizing non-aqueous conditions are applicable from this literature base. Furthermore, prediction of activity, solubility, chemical and structural stability are not routine, and preformulation work must be done on a targeted basis. 

Michael J. Bowker studied chemistry and received his doctorate in Organic Chemistry from the University of Leeds, UK. After 5 years working for a multinational polymer company, he moved to May Baker Ltd., a UK subsidiary of Rhone-Poulenc Sante (now Sanoli-Aventis). He was a Director of Analytical Chemistry for about 15 years and, more recently. Director of Preformulation at Aventis Pharma Ltd. He has been intimately involved in preformulation and solid-state activities, on a worldwide basis for more than 15 years. He has published several research papers and one chapter for a book on pharmaceutical salts and is currently a Director of M. J. Bowker Consulting Limited, a small company undertaking consultancy in salt selection, polymorph selection and pharmaceutical preformulation. 

In the pharmaceutical industry, preformulation is not generally carried out by one department alone. This activity integrates efforts of well-coordinated tasks among many research teams analytical research, basic pharmaceutics, quality control, dosage forms development, and others throughout the... 

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. 

During the preformulation and formulation stages of a parenteral dosage form, the physicochemical properties and excipient compatibility of the pharmaceutical active ingredient (API) should be thoroughly evaluated. The test method requirements are similar to those for oral dosage forms. 

This book is intended to be a practical guide to pharmaceutical preformulation and formulation. It can be used as a reference source and a guidance tool for those working in the pharmaceutical industry or related industries, for example, medical devices and biopharmaceuticals, or anyone wanting an insight into this subject area. The information presented is essentially based on the extensive experiences of the editor and various other contributors who are all actively working in the industry and have learned best practice from their experiences. 

In order to achieve the potential clinical benefits that can be provided by a formulation, as exemplified in Table 7.1, biopharmaceutical input is needed from the start of preformulation, through formulation development, to documentation for regulatory applications. The main objective is to obtain and verify desirable drug delivery properties for a pharmaceutical formulation. The key activities are as follows ... 

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. 

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