Pharmaceutical development from

Charles H. Reynolds, M. Katharine Holloway, and Harold K. Cox, Computer-Aided Molecular Design Applications in Agrochemicals, Materials, and Pharmaceuticals. Developed from a symposium sponsored by the Division of Computers in Chemistry and the Division of Agrochemicals at the 207th National Meeting of the ACS, San Diego, CA, March 13-17, 1994, in ACS Symposium Series 589, American Chemical Society, Washington, DC, 1995. 

Traditionally, in pursuit of their structure-activity relationships, medicinal chemists had focused almost exclusively on finding compounds with greater and greater potency. However, these SARs often ended up with compounds that were unsuitable for development as pharmaceutical products. These compounds would be too insoluble in water, or were not orally bioavailable, or were eliminated too quickly or too slowly from mammalian bodies. Pharmacologists and pharmaceutical development scientists for years had tried to preach the need for medicinal chemists to also think about other factors that determined whether a compound could be a medicine. Table 1.1 lists a number of factors that determine whether a potent compound has what it takes to become a drug. Experimentally, it was difficult to quantitate these other factors. Often, the necessary manpower resources would not be allocated to a compound until it had already been selected for project team status. 

This part of the chapter is based on consideration of the published EPARs at the EMEA s web site. At the time of writing there were more than 60 EPARs available. The contents of the pharmaceutical assessment section of each of these were examined, and detailed notes were made from more than 50 of those documents. The amount of information in the different EPARs varies considerably. Some have specific sections with the heading development pharmaceutics, while others include relevant information in the text without a heading. In some cases there are simple statements to the effect that satisfactory pharmaceutical development data were submitted. Therefore, an attempt has been made to glean information of a general nature, and this will be presented as a discussion of relevant topics by dosage form. 

The services are designed to enable the pharmaceutical and biotechnology customers to reduce overall development time and cost. Thus, research and development concentrates one of this company interests and they continuously accept new assignments for development from the private clients. However, they clearly states that the R D results and products will invariably be patented and the application will be rolled out internationally. Prior to commercialization, the developed products are evaluated and tested under controlled conditions with users and industry groups. 

Oesterle, J., Franks, F., Auffret, T. The influence of tertiary butyl alcohol and volatile salts on the sublimation of ice from frozen sucrose solution Implications for freeze drying. Pharmaceutical Developments and Technology, 3 (2), p. 175-183, 1998. Copyright 1998 by Marcel Dekker, Inc., New York, N. Y., USA... 

The non-random two-liquid segment activity coefficient model is a recent development of Chen and Song at Aspen Technology, Inc., [1], It is derived from the polymer NRTL model of Chen [26], which in turn is developed from the original NRTL model of Renon and Prausznitz [27]. The NRTL-SAC model is proposed in support of pharmaceutical and fine chemicals process and product design, for the qualitative tasks of solvent selection and the first approximation of phase equilibrium behavior in vapour liquid and liquid systems, where dissolved or solid phase pharmaceutical solutes are present. The application of NRTL-SAC is demonstrated here with a case study on the active pharmaceutical intermediate Cimetidine, and the design of a suitable crystallization process. 

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