Determination of the hydrophobicity of organic compounds measured as logPo/w through a new chromatographic method

Setup and validation of shake-flask procedures for the determination of partition coefficients (logD) from low drug amounts

“…The guidelines about log D 7.4 values and their implication for drug development are illustrated in Table 1 (Comer, 2003;Taylor and Triggle, 2007). There are many different approaches which can be used to determine a partition coefficient experimentally (Avdeef, 1993;Donovan and Pescatore, 2002;Gulyaeva et al, 2008;Hitzel et al, n.d.;Kaliszan et al, 2002;Pallicer et al, 2012Pallicer et al, , 2010Ràfols et al, 2012;Stopher and Mcclean, 1990;Takács-Novák and Avdeef, 1996;Valko et al, 2001;Wiczling et al, 2008), but the most direct one is the shake-flask method. In this method, an aqueous solution of a compound is mixed in a flask with an organic solvent (usually water saturated n-octanol).…”

“…The partition coefficient (P) refers to the ratio of compound concentration in each phase and can be determined experimentally by a variety of methods including the well-known shake-flask method (EPA, 1996;OECD 107 Method, 1995), potentiometric methods (Avdeef, 1993(Avdeef, , 1992Ràfols et al, 2012;Takács-Novák and Avdeef, 1996), chromatographic methods (Donovan and Pescatore, 2002;Kaliszan et al, 2002;Liang and Lian, 2015;OECD 117 Method, 2004;Pallicer et al, 2012Pallicer et al, , 2010Wiczling et al, 2008) and others. Besides, lipophilicity can also be estimated using computer software and extensive studies about the accuracy of calculated log P values by different computer software has already been carried out (Chou and Jurs, 1979;Leo, 1987;Mannhold et al, 2009;Pallicer et al, 2014;Tetko et al, 2009).…”

Non-biodegradable polymer particles for drug delivery: A new technology for “bio-active” restorative materials

“…Interestingly, when the H-index 24,25) of each polymer was measured, the polymers with higher ratios of HEMA showed greater hydrophobicity (Table 1). While the polymers with a greater HEMA content can contain more water because of the hydrophilic hydroxyl group, the alkyl chains of the polymerized HEMA in the network possibly act to provide a hydrophobic characteristic.…”

Lipophilicity determination of acidic compounds: MEEKC as a reliable high-throughput methodology

“…However, other experimental methods can be used provided that they show an acceptable level of quality assurance [5]. This is clearly the case of dual-phase potentiometric titration procedures [6,7], commonly used in pharmaceutical research for ionizable drugs with pK a values in a measurable pH range (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), which provide reliable and accurate log P o/w values [8].…”

“…For instance, octanol and C18 phases exhibit a different interaction with hydrogen-bond donor solutes; in the chromatographic system solutes with H-bond acidity are discouraged from partitioning out of the hydro-organic mixture and into the poorer H-bond acceptor C18 phase, whereas octanol (either containing water or other H-bond acceptor moieties) can form hydrogen bonds. Therefore, the introduction of molecular descriptors, either experimental or calculated, allows better correlations between chromatographic retention and log P o/w values [9][10][11][12], but is limited to unionized molecules. However, a lower accuracy from chromatographic methods (±0.5 log units [4]) can be expected in relation to the shake-flask method (±0.3 [3]).…”