Physiochemical data

A comprehensive piece of work on predicting VDSS from physiochemical data was reported by Poulin and Thiel for both rat and human [28]. The experimental input data required is the plasma protein binding, blood cell partitioning, octanokwater partition ratio, and olive oikwater partition ratio. The underlying relationship utilized was ... 

Sartorelli, R, Aprea, C., Cenni, A., Novelli, M.T., Orsi, D., Palmi, S., and Matteucci, G., 1998, Prediction of percutaneous absorption from physiochemical data a model based on data of in vitro experiments. Aim. Occup. Hyg., 42 267-276. 

In rigorously identifying a retinoid or carotenoid species, however, its chromatographic behavior and its absorption spectrum are not sufficient (340). Additional physiochemical data, e.g., mass spectra, NMR spectra, and information on chemical derivatives, are needed (340). 

Voelkel A, Stizemiecka B, Adamska K, Milczewska K (2009) Inverse gas chromatography as a source of physiochemical data. J Chromatogr A 1216(10) 1551-1566... 

Those based on strictly empirical descriptions Mathematical models based on physical and chemical laws (e.g., mass and energy balances, thermodynamics, chemical reaction kinefics) are frequently employed in optimization apphcations. These models are conceptually attractive because a gener model for any system size can be developed before the system is constructed. On the other hand, an empirical model can be devised that simply correlates input-output data without any physiochemical analysis of the process. For... 

The correlation (or lack of correlation) of other physiochemical characteristics has not yet been established. For instance, are all surfactants irritants Can one classify severity by the size of the molecule Can octanol water partition coefficients predict irritation potential does a propensity to partition out of the ocular fluid mean that a compound presents more of an irritation hazard than one which is more water soluble Theoretically, these data should reflect the ability of a compound to penetrate the eye and cause an irreversible lesion. However, until definitive data are available, physical and chemical parameters will probably have limited utility in an overall assessment of irritation. 

When large numbers of chromatograms are analyzed visually from chart paper or tabular data, it is difficult to detect minor (or perhaps major) significant differences that may be present in samples from different locations or differences that could be attributed to changing physiochemical processes. A typical gas chromatogram of a PCB mixture (Figure 2) represents a 1 1 1 1 mixture of Aroclors 1242, 1248, 1254, and 1260. It contains more than 100 component peaks, of which 69 were selected for use in these analyses. 

As part of the preformulation activities, investigations include physiochemical character, purity, solubility, stability, and optimal pH studies. In preparation for clinical studies, potential product formulations considering route of administration and solution stability are also studied. Unique to dosage form development studies for lyophilized products, thermal analysis of the drug substance and product formulations are also necessary. Data generated during this phase of product development is useful for future development activities, along with validation. 

Development studies, summarized within a distinct report on the physiochemical aspects, drug substance attributes, and finished product characteristics, become critical parts of the validation package. Such data is also valuable for future integration into a manufacturing operation. This includes the scientific rationale for formulating and bulk-handling procedures, lyophilization processing parameters, finished product analysis, and stability requirements. 

Refinements of the RfC have utilized mechanistic data to modify the interspecies uncertainty factor of 10 (Jarabek, 1995). The reader should appreciate that with the inhalation route of exposure, dosimetric adjustments are necessary and can affect the extrapolations of toxicity data of inhaled agents for human health risk assessment. The EPA has included dosimetry modeling in RfC calculations, and the resulting dosimetric adjustment factor (DAF) used in determining the RfC is dependent on physiochemical properties of the inhaled toxicant as well as type of dosimetry model ranging from rudimentary to optimal model structures. In essence, the use of the DAF can reduce the default uncertainty factor for interspecies extrapolation from 10 to 3.16. 

Intravenous Compatibility Module Data for automatic screening of physiochemical compatibility and incompatibility of IV preparations. 

Figure 5 Ethyl ether-ethyl alcohol vapor-pressure diagram at 50°C. (Data from J Timmermans. Physiochemical Constants of Binary Systems in Concentrated Solutions. Volume 2. New York Interscience, 1960, p 401.)...

As of 1981, when theEuropeanchemicalspolicy was implemented, theEuropean Union required the submission of base set test data for physiochemical, environmental fate, toxicological properties and health effects, and ecotoxicity parameters for new... 

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