Physicochemical Considerations

The bisindole alkaloids of Catharanthus exhibit ambiphilic behavior in solution, owing, in large part, to their gross lipophilic character combined with the presence of four nitrogen atoms of varying basicity. The upper 

The molecular weight of a typical bisindole alkaloid is in excess of 800 g/mol, yet the high degree of unsaturation (9 rings) and shared bonds (6 

X-Ray diffraction analyses of vincristine methiodide (39) and vinzoli-dine 1-naphthalene sulfonate (40) provide atomic coordinates of compounds that are either modified in the velbanamine portion (alkylation at N-6, Fig. 3) or in the vindoline portion (a spiro-fused oxazolidinedione at C-3 and C-23, Fig. 4). These structures show a chair-boat conformation for ring C with C-8 exhibiting an endo pucker. Ring D is clearly in a chair conformation, but, in contrast to the conclusions drawn from C-NMR studies, the N-6 -C-7 bond is axial relative to the piperidine ring. 

As previously noted, the partition properties of the bisindole alkaloids tend to be lipophilic. The octanol-water partition coefficients of several bisindole derivatives have been measured and compared to various bio- 

Correlation of bisindole alkaloid tubulin binding affinity (K ) with partition coefficients at pH 7.4 [data from Owellen et al. (41)]. 

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The selection of a particular type of reduction depends on technical feasibiUty and the economics of the process as well as on physicochemical considerations. In particular, the reducing agent should be inexpensive relative to the value of the metal to be reduced. The product of the reaction, RX, should be easily separated from the metal, easily contained, and safely recycled or disposed of. Furthermore, the physical conditions for the reaction should be such that a suitable reactor can be designed and operated economically. 

Physicochemical Considerations. The determination of the equihbrium constant for the reaction C2H5OH + CH3COOH = C2H5OOCH3 + H2O has been the subject of a number of investigations over the temperature range of 40—300°C (62). The... 

The physicochemical considerations discussed in Chapter 3 that govern the passage of drugs across biological barriers are applicable to both excretory and absorptive phenomena. 

The three main processes by which atmospheric deposition of pesticides to the lakes occurs are wet deposition (rain and snow), dry deposition (particulates), and air-water gas exchange. For many of the banned pesticides, gas exchange across the air-water interface, in particular, is often the dominant deposition process, when compared with precipitation and dry particle exchange [42-44], The physicochemical considerations, as well as descriptions of calculation models for atmospheric deposition to lakes, rivers, and the oceans, have been reviewed extensively [45-47]. 

Viruses are complex particles, entering the cells by fusion of their envelope to the plasma membrane or by endocytosis followed by the escape of the capsid by membrane fusion or lysis (Sodeik, 2000). The diameter of the viral particle could be several hundred nanometers, implying a very inefficient diffusional movement in the cytoplasm, based on those physicochemical considerations that were discussed above (Kasamatsu and Nakanishi, 1998). Despite these limitations, those viruses that replicate in the nucleus have evolved sophisticated mechanisms to ensure a highly efficient nuclear delivery of their genetic material. Since these mechanisms may provide a conceptual framework to design novel non-viral delivery systems, we shall review some of the key elements that account for the nuclear targeting of certain viruses. 

Table 21.6 summarizes the available delivery platforms in respect of their relevant physicochemical considerations in relation to the type of drug that can be delivered, and the ability to sustain and control the delivery process. More substantive descriptions of each formulation type are now discussed. 

Moghimi, S., L. Ilium, and S. Davis. 1990. Physiopathological and physicochemical considerations in targeting of colloids and drug carriers to the bone marrow. Crit Rev Ther Drug Carrier Syst 7 187. 

On the contrary, at x > x[f, there is a deficit of the B atoms because the reactivity of the A surface exceeds the flux of these atoms across the ApBq layer. Therefore, on reaching interface 1, each B atom is combined at this interface into the ApBq compound. In this case, there are no excessive B atoms for the formation of other compounds enriched in component A. Thus, none of compound layers located between A and ApBq can grow at the expense of diffusion of component B. This almost obvious result following in a natural way from the proposed physicochemical considerations is crucial for understanding the mechanism of formation of multiple compound layers. Perhaps, just its evident character is the main reason, firstly, why many researchers in the field have overlooked it and, secondly,... 

It is worth mentioning that physicochemical considerations predict the opposite influence of the degree of deficiency of a chemical compound on the values of the reaction- and self-diffusion coefficients. The former must decrease with increasing compound deficiency, while the latter is known to increase with its increasing. This seems to be the case, for example, with oxides like FeO, Fe3C>4, MnO, CoO, etc., though complicating factors often mask these effects. 

Restrictions on the number of simultaneously growing compound layers, following from physicochemical considerations, 134,137,139,141 are... 

From the EPMA data in Table 3.7 (see also Fig. 3.14a), it follows that the Co-bordering layer consists of the y and yi phases, with the last phase being dominant. Another important point is a smooth concentration distribution within the bulk of this layer, without any discontinuity due to the existence of the two-phase y + Yi field of 85.4-87.4 at.% Zn on the phase diagram, indicative of a diffusionless transformation. Note that the restrictions on the number of simultaneously occurring layers, following from physicochemical considerations, are clearly inapplicable to compounds which are formed by a diffusionless (shear) mechanism. 

Law D, Kril SL, Schmitt EA et al. (2001) Physicochemical considerations in the Preparation of Amorphous Ritonavir (polyethylene glycol) 8000 Solid Dispersions. I Pharm Sci 90(8) 1015-1024... 

This chapter considers the specific physicochemical considerations of various chromatographic modes and provides strategic considerations in HPLC separations as well as heuristic approaches and productivity considerations in scale-up operations. 

VI. SPECIFIC PHYSICOCHEMICAL CONSIDERATIONS ON THE INDIVIDUAL CHROMATOGRAPHIC MODES... 

VI. Specific Physicochemical Considerations on the Individual Chromatographic Modes 117... 

Shek, R N., Suntres, Z. E., and Brooks, J. I. (1994), Liposomes in pulmonary applications Physicochemical considerations, pulmonary distribution and antioxidant delivery, J. Drug Targe., 2, 431—442. 

Hussain, A. A., Bawarshi-Nassar, R., and Huang, C. H. (1985), Physicochemical considerations in intranasal drug administration, in Chien, Y. W., Ed., Transnasal Systemic Medication, Elsevier, Amsterdam, pp. 121-138. 

Xu,P, and Chien, Y. W. (1991), Enhanced skin permeability for transdermal drug delivery Physiopathological and physicochemical considerations, Crit. Rev. Ther. Drug Carrier Syst., 8(3), 211-236. 

Westerhoff, H. V. Welch, G. R. (1992). Enzyme organization and the direction of metabolic flow physicochemical considerations. In Current Topics in Cellular Regulation, Vol. 33 (Stadtman, E. R. and Chock, P. B., eds.), pp. 361-390, Academic Press, New York. 

After the crystallization of flie product, solvents must be removed in order to obtain die minimum amount of residual solvents compatible with safety considerations and/or physicochemical considerations including stability, processability and occasionally microbiological quality (see Chapter 16.2). Different situations can be encountered. 14.21.1.3.1.4.2.1 Solvent outside the crystal... 

The following physicochemical considerations have to be taken into account in discussions on... 

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