Solubility and Partitioning VI: Octanol Solubility and Octanol–Water Partition Coefficients

Yalkowsky, Samuel H.; Valvani, Shri C.; Roseman, Theodore J.

doi:10.1002/jps.2600720808

Cited by 188 publications

(86 citation statements)

References 7 publications

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“…These equations apply partition coefficient (log P) and melting point (mp) to calculate molar solubility of compounds. [32][33][34] Experimental Method: The solubility of drug and esters was determined in a pH range of 2.2 to 8. The buffers were prepared similar to the pH stability test.…”

Section: Study Of Mtx-pegs Stabilitymentioning

confidence: 99%

Synthesis and Characterization of Methotrexate Polyethylene Glycol Esters as a Drug Delivery System

et al. 2010

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147Methotrexate (amethopterin, 4-amino-N 10 -methyl petroyl glutamic acid, MTX) is a drug that has been used clinically since 1953 for treatment of many tumors especially acute lymphoblastic anemia. It has also been used for several other diseases like choriocarcinoma, psoriasis, sarcoidosis and trophoblastic tumors. 1,2) However some limitations restrict the use of methotrexate including high toxicity due to its low specificity and short plasma half life. In recent decades some methods have been developed to overcome these limitations that polymer conjugation has been of more importance. Conjugation of methotrexate with natural and synthetic long chain polymers like human and rabbit serum albumins, 3,4) poly L-lysine, 5,6) dextran, 7) poly hydroxyethyl methacrylate (HEMA), 8) poly spartamide 9) and gelatin 10,11) proves the importance of methotrexate as an strategic drug and its necessities of polymer conjugation. 29) Polyethylene glycol (PEG) is the most common polymer ever used for conjugation. The researchers have mentioned many rationales for conjugation with PEG (pegylation) including increased water solubility, controlled permeability through biological barriers, longevity in blood stream, controlling of release, overcoming tumor resistance, increased antitumor effect and reduced protein immunogenicity. [12][13][14][15] Among the small molecules, anticancer and antiviral drugs have been in priority for pegylation such as paclitaxel, 16,17) podophyllotoxin 18) and 6-mercaptopurin 19) for increasing water solubility, amphotericin B for decreasing drug toxicity and side effects, 20) doxorubicin for increasing efficacy 21) and in case of campthotecin for increasing solubility, efficacy and plasma circulation half life.22,23) PROTHECAN ® , the ester of campthotecin and mPEG40000D is a typical conjugate that is under clinical phase II. 24)In despite of extensive researches on physicochemical properties of produced pegylated forms of other drugs including water solubility, in vitro and in vivo bond stability (the study of different linkages and spacers between drug and PEG) 17,[25][26][27] and in vivo fate of conjugates, 12,21,28) there is no enough information about different polymer conjugates of methotrexate.29) Furthermore, as the most of polymer conjugates contain a link between a-carboxyl group of methotrexate and amino or hydroxyl group of synthetic or natural polymers, it is expected to obtain the similar physicochemical properties including partitioning and solubility in different conjugates. In the current study, as part of our aim to improve physicochemical and biopharmaceutical properties of MTX to achieve a better drug delivery system, synthesis of esters of MTX with PEGs of different molecular weight (at low, medium and high molecular weight) and evaluation of the physicochemical properties of MTX-PEGs were described. To the best of our knowledge, no reports on the synthesis and application of the esters of MTX-PEGs as novel drug delivery for MTX has been published. Methotrexate (MTX) is one...

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Section: Study Of Mtx-pegs Stabilitymentioning

confidence: 99%

Synthesis and Characterization of Methotrexate Polyethylene Glycol Esters as a Drug Delivery System

et al. 2010

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“…In contrast, the other derivatives display an isotope effect which is smaller than calculated by 0.0036 f 0.0010. If genuine, this difference may point to a subtle 'second-order' perturbation by the group C2H,-N(3) and/or to perturbation of self-association phenomena [29] (see Discussion).…”

Section: Woupmentioning

confidence: 97%

Isotope Effects on the Lipophilicity of Deuterated Caffeines

Bechalany¹,

Tayar²,

Carrupt³

et al. 1989

Helvetica Chimica Acta

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In the present study, it is confirmed that the deuteration ofC-H groups is accompanied by a small but genuine decrease in lipophilicity. The lipophilicity of deuterated isotopomers of caffeine was measured by reversed-phase HPLC. Overall, lipophilicity was shown to decrease when going from unlabelled caffeine to the three isomeric trideuterated caffeines, then to the three isomeric hexadeuterated caffeines, and finally to nonadeuterated caffeine. In addition, position-specific effects were also proven. E.g. (7-methy[-'H3)caffeine experienced a smaller isotope effect than its two positional isomers. Both a cavity factor (decreased volume of deuterated isotopomers) and intramolecular electronic effects are postulated to operate.

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“…Yalkowsky et al (1983) (10) which was tested on the solubility of 12 pharmaceuticals and the mean percentage deviation was 85.1 (± 21.6) % (Jouyban, 2009). Sepassi and Yalkowsky (2006) (Stovall et al, 2005b).…”

Section: Solubility In Organic Solventsmentioning

confidence: 99%