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Principles and Methods of Ocular Pharmacokinetic Evaluation
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
One of the primary determinants of the penetration of any chemical into ocular tissues and compartments is the partition coefficient of the compound under investigation. The partition coefficient is a measure of the relative solubility of a compound in a lipid vs. an aqueous phase. These values are often given as the ratio of solubility of a substance in an organic solvent (e.g., ether, isobutanol, octanol) or oil (e.g., olive oil) to that in water. High values (e.g., 10 to 10-2) indicate that a compound is very lipid soluble, while low values (e.g., 10-4 to 10-6) conversely indicate a high aqueous solubility, or lipophobicity. It is important to have some knowledge of this determinant, especially in relation to the route of access that the compound will have relative to the eye. For example, a compound that is lipid soluble will have less difficulty passing through the cornea if applied as a topical drop or if it has access to the ocular surface, than will a more water-soluble compound. This is due to the composition of the cornea, with its highly lipid-containing, cellular epithelium covering the anterior surface. An excellent illustration of this might be the transcorneal penetration of lipid- and water-soluble steroids. With the epithelium present, only the lipid-soluble drugs penetrated the entire cornea, while in the absence of epithelium, no marked differences occurred in the penetration of lipid- and water-soluble steroids.10
Disposition and Toxicokinetics
Published in P. K. Gupta, Brainstorming Questions in Toxicology, 2020
Assume two drugs (identical molecular weight, same dose given): one neutral drug (Drug A) and one acidic drug (pka = 7.4, Drug B). Drug A and the unionized form of drug B have the same partition coefficient. The fraction unbound in plasma and tissue is 0.5 for both drugs. Drug B will enter tissues somewhat slower than Drug A.
Radioactive Se And Te Labeled Imaging Agents
Published in Garimella V. S. Rayudu, Lelio G. Colombetti, Radiotracers for Medical Applications, 2019
One of the principal attractions of intracellular pH shift as a mechanism of localization is the flexibility it provides in the design of new agents. The partition coefficient-pH profile can be controlled by using groups of higher or lower lipophilicity and by changing the pK of the basic nitrogen atoms by adjusting the chain length between them and by electron donating or withdrawing moieties. Using these techniques one can design radiopharmaceuticals that change from lipid-to-water-soluble at any desired pH and have high or low ratios for partition coefficients between pH 7.4 and 7.0.
Preparation of technetium-99m labeled ibuprofen by direct route and technetium-99m tricarbonyl route: a comparison of in vivo behaviors
Published in Drug Development and Industrial Pharmacy, 2020
Kubra Durkan, Cigdem Ichedef, Ayfer Yurt Kılcar, Mesut Arıcı, Eser Ucar
Lipophilicity refers to the ability of any chemical compound to dissolve in apolar solvents such as fats, oils, lipids. While hydrophilic substances tend to dissolve in water, lipophilic materials tend to dissolve in oils. It is expressed as a ratio of partition coefficient in octanol to water (Coctanol/Cwater). The magnitude of this ratio is directly proportional to the fact that the substance is lipophilic. The value of this ratio is called P and the logarithm of this value is taken and used as the symbol of lipophilicity (LogP) [26,27]. Similarly, in the present study, the partition coefficients of the radiolabeled complexes were determined by distribution in 1-octanol and PBS. The lipophilicity of the 99mTc-ibu (logP= −0.2 ± 0.01) was much more than that of the 99mTc(CO)3-ibu (logP= −1.1 ± 0.12). The logP value of ibu was calculated as 3.48 [28]. The experimental results suggest that the 99mTc(CO)3 moiety can decrease the lipophilicity of the complex which can result in biological behavior changes. In another study, meloxicam has labeled with [99mTc(H2O)3(CO)3]+ precursor to synthesized 99mTc-(CO)3-meloxicam complex [25]. It is reported that the partition coefficient of the radiolabeled meloxicam via the tricarbonyl route was found relatively low than direct route labeling [8].
Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation
Published in Drug Development and Industrial Pharmacy, 2019
Nini Li, Ling Fan, Biao Wu, Genlai Dai, Chengjun Jiang, Yan Guo, Dianlei Wang
The shake-flask method was employed to determine the oil-water partition coefficient of azilsartan. In brief, 0.5 mL of n-octanol solution was taken as the oil phase, and 5 mL of water-buffer solution was used as the aqueous phase. After equilibrium, the sample was centrifuged and the upper oil phase was diluted before analysis by the HPLC method. The concentrations of azilsartan in the aqueous phase were calculated according to Cw = (C – Co)/10. The oil-water partition coefficient P=Co/Cw. C is the concentration of azilsartan initially added in n-octanol solution. Co is the concentration of azilsartan in the oil phase, and Cw is the concentration of azilsartan in the aqueous phase.
Rutin–phospholipid complex in polymer matrix for long-term delivery of rutin via skin for the treatment of inflammatory diseases
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
The partition coefficient of a drug molecule is an important property in the absorption of drug across the biological membrane. The drug molecule should have a partition coefficient (octanol/water) in the range of 1–4 [49,50] for effective dermal and/or transdermal application. Partition coefficient value when exceed 3 may retard drug permeation via skin due to the difficulties in permeating hydrophilic epidermis/dermis beneath the SC [51,52]. Partition coefficient values of pure rutin were found to be at 7.04 ± 0.28 (ocanol/water), 6.36 ± 0.33 (octanol/phosphate buffer pH 6.8) and 8.10 ± 0.44 (octanol/acetate buffer pH 4.5). The most satisfactory partition coefficient value for RNPs was observed at 3.11 ± 0.08 in octanol/phosphate buffer pH 6.8 partitioning medium. The complex formation of rutin with PC is thus significantly decreased its partition coefficient than the free rutin. It indicates the suitability of RNPs for dermal application. The RNPs will remain deposited in the skin for long-term site specific delivery of rutin.