Principles and Methods of Ocular Pharmacokinetic Evaluation
David W. Hobson in 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
General toxicology
Timbrell John in Study Toxicology Through Questions, 2017
(d) The partition coefficient of a chemical is a measure of its lipid solubility. It is determined by measuring the amount of a chemical present in the aqueous and organic phases after an aqueous solution of the chemical is shaken with an organic solvent (or oil). The ratio of the concentration in the organic phase to the concentration in the aqueous phase is the partition coefficient. It may be expressed as the of this ratio . The aqueous phase may be water or buffer at a particular (e.g. 7.4 for relevance to biological systems). The organic phase used is often chloroform although other organic solvents such as octanol and even olive oil may be used. Clearly the combination must be specified when the value is quoted.
Cyclodextrins and Skin Disorders: Therapeutic and Cosmetic Applications
Andreia Ascenso, Sandra Simões, Helena Ribeiro in Carrier-Mediated Dermal Delivery, 2017
The partition coefficient (K in Eq. 13.1) of the drug is also an important parameter for optimal dermal absorption. Drug solubility and thermodynamic activity have been reported to affect the partition coefficient. Thus, CyDs’ ability to increase drug solubility positively affects the partition coefficient for enhanced drug absorption [62]. The prevention of skin metabolism or bio- conversion of some drugs have also been described as the possible way by which CyDs increase drug availability and subsequent drug penetration of the stratum corneum. For instance, a 35% reduction in dexamethasone degradation was observed when b-CyD and HP-b-CyD complexes were used instead of the free drug [54].
A thermodynamic study of F108 and F127 block copolymer interactions with liposomes at physiological temperature
Published in Journal of Liposome Research, 2022
Obed Andres Solis-Gonzalez, Juan Ramon Avendaño-Gómez, Aarón Rojas-Aguilar
The analysis of peaks was carried out using the Nano-ITC software (NanoAnalyzeTM Data Analysis, TA Instruments, New Castle, Delaware), and the nonlinear fitting was determined with Origin® software (OriginLab Corporation, Northampton, MA). The partition coefficients and enthalpies for the EYPC/F108 and EYPC/F127 systems were determined based on the Heerklotz model of interactions between surfactants and liposomes, for which the block copolymer can be considered a non-ionic surfactant. The main advantage of this model is that it has been successfully employed in liposome/poloxamer partitioning experiments (Wu et al. 2009, Wu and Lee 2009). Briefly, the partition coefficient (K) is determined according to the molarities of all compounds that comprise the system using the following equation: W is the water molarity (55.5 M), and
Preparation of an isorhamnetin phospholipid complex for improving solubility and anti-hyperuricemia activity
Published in Pharmaceutical Development and Technology, 2022
Fengmao Zou, Honghui Zhao, Aijinxiu Ma, Danni Song, Xiangrong Zhang, Xu Zhao
The distilled water was added to an equal volume of 1-octanol. The mixed solution was shaken in the air bath thermostatic oscillator at 37 °C for 24 h. The mixture was left to stand for 12 h and then the two phases were collected in the 100 ml conical flask. Next, an excess of ISO or ISO-PC was added to 10 ml of the 1-octanol phase. After being sonicated for 5 min, the solution was centrifuged at 4000 r/min for 15 min. The concentration of the 1-octanol phase (C1) was determined by the UV spectrophotometer. About 1 ml of the above 1-octanol phase was mixed with 1 ml of the aqueous phase and shaken at 37 °C for 24 h to equilibrate the ISO or ISO-PC between the two phases. The two phases were separated by centrifugation, and the aqueous phase was taken to determine the concentration (C2). The octanol-water partition coefficient (P) was calculated by the formula as follows: P = (C1-C2)/C2.
Lipid, water, and protein composition to facilitate kinetic modeling of the auditory pathway
Published in Toxicology Mechanisms and Methods, 2019
Nadja Grobe, Latha Narayanan, Dominique N. Brown, Sarah T. Law, Isaie Sibomana, Pavel Shiyanov, Nicholas V. Reo, C. Eric Hack, Teresa R. Sterner, David R. Mattie
A physiologically based pharmacokinetic (PBPK) model for JP-8 exacerbated ototoxicity requires partition coefficients for jet fuel constituents, which ultimately results in increased use of animals considering the complex composition of the military aviation fuel and the limited availability of the target tissues. PBPK models are sets of mathematical equations that describe the absorption, distribution, metabolism, and elimination of a chemical, drug, or mixture in order to predict the concentration at any given target tissue in the body. To simulate target site dosimetry, PBPK models contain compartments that correspond to specific tissues or groups of tissues. Physiological parameters such as organ volumes and blood flows can be altered to allow a PBPK model to describe different species, ages, or disease states. One parameter necessary to describe chemical movement is the chemical- and tissue-specific partition coefficient. A partition coefficient is the equilibrium ratio of the unbound chemical between two compartments; for PBPK modeling, the plasma:air partition coefficient plus a tissue:plasma partition coefficient is required for every tissue or tissue group represented in the model (Robinson et al. 2007).
Related Knowledge Centers
- Chemical Compound
- Chemistry
- Ionization
- Lipid Bilayer
- Blood Plasma
- Partition Equilibrium
- Pharmacy
- 1-Octanol
- Distribution
- Octanol-Water Partition Coefficient