Pharmaceutical research value

In conclusion, it is likely that computational approaches for metabolism prediction will continue to be developed and integrated with other algorithms for pharmaceutical research and development, which may in turn ultimately aid in their more widespread use in both industry and academia. Such models may already be having some impact when integrated with bioanalytical approaches to narrow the search for possible metabolites that are experimentally observed. Software that can be updated by the user as new metabolism information becomes available would also be of further potential value. The held of metabolism prediction has therefore advanced rapidly over the past decade, and it will be important to maintain this momentum in the future as the hndings from crystal structures for many discrete metabolic enzymes are integrated with the diverse types of computational models already derived. 

Further complicating the matter of software as property and its place in pharmaceutical research is consideration of the very place of property in health care. The value of health, most philosophers agree, is intrinsic. It exists for itself and for no other reason. As such, health, like life and liberty, is an important and powerful end or goal. Ownership of property is a lesser end or goal. 

The book is organized into eight chapters. Chapter 1 describes the physicochemical needs of pharmaceutical research and development. Chapter 2 defines the flux model, based on Fick s laws of diffusion, in terms of solubility, permeability, and charge state (pH), and lays the foundation for the rest of the book. Chapter 3 covers the topic of ionization constants—how to measure pKa values accurately and quickly, and which methods to use. Bjerrum analysis is revealed as the secret weapon behind the most effective approaches. Chapter 4 discusses experimental... 

The use of direct UV spectrophotometry to measure sample concentrations in pharmaceutical research is uncommon, presumably due to the prevalence and attractiveness of high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) methods. Consequently, most researchers are unfamiliar with the value of UV detection, mainly that it is generally much faster than other methods - a very important asset in high-throughput screening. 

However, from our point of view, there remains a lack of sufficiently precise and reliable methods to compute thermodynamic water solubility. The majority of methods work only for congeneric series of compounds, and many have not been developed to function in areas of pharmaceutical research using drug-like molecules. Most of the methods do not use the three-dimensional structure of the compounds, while some depend on previous knowledge of certain experimental properties of the compounds of interest. Moreover, all of the methods are dependent upon the quality of solubility values in the training set used to develop the model indeed, this latter point is a critical limitation that has a major influence on solubility estimations. 

On this point, Grabowski and Vernon (1990,1994) estimate rates of return from investment in pharmaceutical research and development, and report values slightly higher than the associated cost of capital. In their latter study they conclude the estimated mean return on pharmaceutical industry new chemical entity (NCE) introductions forthe first half ofthe 1980s was 11.1% compared with the estimated (real) cost of capital of 10.5% over the same period (p. 404). This finding also suggests that one is unlikely to find major unexploited opportunities. Still, without determining a social optimum, one cannot make firm conclusions about the sufficiency of resources directed toward these activities. 

In Chapter 12 Cremieux and his coauthors, based on a systematic review of the empirical evidence, conclude that international and country-specific studies as well as analyses of individual diseases all indicate that, since about 1950, the period covered by their review, investments in pharmaceutical products have generally been worthwhile investments. With rates of return over 10 to 1 based on measures of increased life expectancy alone, not even considering improved quality of life, pharmaceutical research has successfully provided developed countries with better health at a cost that has been far exceeded by the value of improved longevity. Not considering the value of improvements in quality of life, such as from reductions in pain, emotional health, and symptoms from short-term illnesses, should lead to a substantial underestimate of the value of health. 

Research -Development Production =>Marketing Sales Distribution Figure 1 Pharmaceutical industry value chain. 

To withstand the threats on the record of pharmaceutical research and development productivity, numerous so-called paradigm changes have been announced over the past 10-15 years, all aimed at resolving major bottlenecks along the value chain of drug discovery [10-12],... 

The Pharmaceutical Research and Manufacturing Affiliates (PhRMAG) was founded in 1999, and is based in Dubai (UAE). Its objective is to represent the pharmaceutical industry in dialogue with governments in healthcare issues and to communicate the value of innovation and research. Its membership is mainly the Middle East affiliates of European and American pharmaceutical companies that are active in the five Gulf States (Kuwait, Bahrain, Qatar, UAE and Oman). 

The most common methods used for pharmaceutical pK values are based on pH measurements, Eqs. (3-8). Thus, they cannot be interpreted with greater accuracy than 0.02 pKa unit [see the definition in Section 2.1, Eq. (1)]. This level of precision and accmacy should always be the aim in determining pK values for inclusion in the drug sciences literature. Potentiometric titrations [Eqs. (3-4)] are often performed with this level of accmacy, primarily for compounds with either a single ionization step or for multiple ionizations with >4 log units between the pKa values. The careful use of precise pH meters (e.g., the series of Beckman Research models, or the corresponding Radiometer, Orion, or Metrohm instruments) for the determination of pH data means that reproducibility for replicate measurements may be rather better than 0.02. In the author s experience, these instruments may be calibrated with a reproducibility of 0.002 pH imit, which can be maintained (with proper temperature control and exclusion of CO2) for at least 8 h. This does not imply accuracy of 0.002 pH unit, which is not possible according to the current definition of pH. Spectrophotometric [Eq. (5)] and solubility-pH dependence [Eqs. (7-8)] methods are potentially capable of similar accuracy, but often do not give results better than 0.05 pKa unit, due to the inevitable inclusion of additional sources of error from the absorbance or concentration measurements. 

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