Penetrants physico-chemical properties

Uptake by plants, insects and fungi. Penetration into plants for systemic action and through the outer membranes of insects and fungi is a complex process which may involve compound-specific metabolic or active processes. Rigorous relationships with physico-chemical properties cannot therefore be expected. Nevertheless some broad general guidelines can be deduced. 

Preliminary predictions of absorption of a substance can be made from its physico-chemical properties if no other information is available. Also elaborate computer programs are available that make predictions about, e.g., dermal penetration or metabolic pathways. However, these systems have often not been extensively validated against appropriate experimental data and it is not always certain if the results obtained in such models reflect the situation in vivo. On this basis, modeled data should only be used for risk assessment purposes where it is supported by other kinds of evidence. 

As the pharmacokinetic properties of the azomethine prodrugs of (7 )-a-methyl-histamine (12) were found to strikingly depend on their physico-chemical properties, it was attempted to quantify the relationship between lipophilicity and CNS penetration of the benzophenone derived imines [50], The main obstacle to the experimental measurement of the azomethines log P values was the competing hydrolysis of the... 

A description of transdermal drug delivery has been produced which is based on the physicochemical properties of the permeant. At this time transdermal delivery is limited to the administration of potent drugs. Higher doses may be accessible if penetration enhancers are incorporated into the formulation. The kinetic model shows what properties these should have and that they are a function of the physico-chemical properties of the drug. Various loss processes, e.g. microbial biotransformation, skin enzyme metabolism can be identified but cannot, as yet, be quantified. 

One of the simplest early free-volume diffusion models was formulated in (51,52,60). The concept of this model was considered an advance, because some of the parameters required to describe the concentration dependence of the diffusion coefficient could be obtained from the physico-chemical properties of the polymer and penetrant. The relation proposed for the calculation of the thermodynamic diffusion coefficient, DT, was (51,60) ... 

Skin-snake-model percutaneous absorption Relationships between the in vitro permeability of basic compounds through shed-snake skin as a suitable model membrane for human stratum corneum and their physio-chemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of the nonionized forms of the compounds. Steady-state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady-state penetration data and relationships between these parameters and the physico-chemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the MWs and the partition coefficients of basic compounds. 

When the pharmaceutical formulation of an active compound is ineffective, slight chemical modifications or formation of bioreversible derivatives (esters, amides, peptides) can improve its physico-chemical properties (lipophilicity, pK, polarity) and optimize the dissolution rates in the biological fluids and the passage through the very first biological membranes (cutaneous, intestinal, etc.). The global result is better penetration into the organism. Compared with the pharmaceutical formulation mentioned above, this process can be considered as a chemical formulation and will be considered in Chapter 39. 

Organotin compounds are the most rapidly-expanding class of organometallic compounds. U.S. production alone is estimated to be greater than 30,000 tons (Zuckerman et al. 1978). The reason for rapid market penetration in both existing and novel products and applications is undoubtedly the diversity of physico-chemical properties possessed by organotin compounds. Use as... 

Phase I - an environmental impact assessment for the drug based on physico-chemical properties, its likely penetration into the environment and its metabolic profile in target patient animals and, if a certain trigger value is exceeded ... 

After inhalation exposure, the absorption of Cd compotmds varies greatly depending on the physico-chemical properties of the Cd compounds involved, site of deposition in the lungs and particle size [22]. In the Itmgs, deposition, mucociliary clearance, and alveolar clearance determine the absorption of inhaled particles. Large particles, dusts (>10 pm in diameter) tend to be deposited in the upper airways, while small particles, fumes, cigarette smoke (approximately 0.1 pm in diameter) penetrate into the alveoli, which are the major site of absorption. Between 50-100% of Cd in the alveoli are transferred to the blood. In the average... 

In the beginning of the last century, it was observed that the permeability of a substance across a cell membrane is proportional to the relative partition coefficient of the permeating substance between phases of oil and water. In later years, it was found that the product of the permeability coefficient P and the square root of the molecular weight of a permeant shows a better correlation with the partition coefficient than does permeability alone. This correlation has lead to the idea that permeation is limited not only by the hpid solubility of the permeant but also by a screen-like property of the membrane because small molecules penetrate faster than would be predicted from their oil-water partition coefficients. For larger molecules, however, one would expect a product of permeability with the cube root, rather than the square root, of the molecular weight to be more closely correlated with the oil-water partition coefficient. Likewise, the apparent partition coefficient to the membrane plays a major role for the transport processes across the membrane. In strict physico-chemical terms, a membrane is not a phase, but it is most common to treat it as such anyway. 

During the modification process of the bitumen, chemical and physico-chemical changes, depending on the type of modifier/additive used, occur. These changes affect the characteristic properties of the bitumen such as penetration, softening point, viscosity, cohesion, resistance to hardening, elastic recovery and Fraass breaking point. 

Granules of starch are found in the interior of the vascular bundle (Figure 9.4). Silica bodies are also found in great number on the fiber strand. They attach themselves to circular craters which are spread relatively uniformely over the strand s surface. The silica bodies are hard, but can be dislodged mechanically. The removal of silica bodies leaves behind perforated silica-crater, which would enhance penetration of matrix in composite fabrication leading to interfacial adhesion stronger [25]. A compilation of the chemical composition and physico-mechanical properties of oil palm fiber... 

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