Estimation of drug solubility in water, PEG 400 and their binary mixtures using the molecular structures of solutes

Ghafourian, Taravat; Bozorgi, Atefeh Haji Agha

doi:10.1016/j.ejps.2010.04.016

Cited by 13 publications

(23 citation statements)

References 44 publications

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“…Interestingly we did not find Tm to significantly influence drug solubility in PS80 and PEG400. This was surprising as Tm has been suggested previously to be important in attempts to model drug solubility in PEG400 (40,41). The latter studies examined the solubility of a dataset of 92 molecules in PEG400 resulting in solubility differences of more than 50,000-fold.…”

Section: Discussionmentioning

confidence: 93%

Computational Prediction of Drug Solubility in Lipid Based Formulation Excipients

et al. 2013

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PurposeTo investigate if drug solubility in pharmaceutical excipients used in lipid based formulations (LBFs) can be predicted from physicochemical properties.MethodsSolubility was measured for 30 structurally diverse drug molecules in soybean oil (SBO, long-chain triglyceride; TGLC), Captex355 (medium-chain triglyceride; TGMC), polysorbate 80 (PS80; surfactant) and PEG400 co-solvent and used as responses during PLS model development. Melting point and calculated molecular descriptors were used as variables and the PLS models were validated with test sets and permutation tests.ResultsSolvation capacity of SBO and Captex355 was equal on a mol per mol scale (R2 = 0.98). A strong correlation was also found between PS80 and PEG400 (R2 = 0.85), identifying the significant contribution of the ethoxylation for the solvation capacity of PS80. In silico models based on calculated descriptors were successfully developed for drug solubility in SBO (R2 = 0.81, Q2 = 0.76) and Captex355 (R2 = 0.84, Q2 = 0.80). However, solubility in PS80 and PEG400 were not possible to quantitatively predict from molecular structure.ConclusionSolubility measured in one excipient can be used to predict solubility in another, herein exemplified with TGMCversus TGLC, and PS80 versus PEG400. We also show, for the first time, that solubility in TGMC and TGLC can be predicted from rapidly calculated molecular descriptors.

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Section: Discussionmentioning

confidence: 93%

Computational Prediction of Drug Solubility in Lipid Based Formulation Excipients

et al. 2013

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“…Also it has been shown that aqueous solubility has indirect correlation with the molecular volume of the compounds. 46 Based on this fact, the following equation was proposed: logS w = -0.902 + i Solute + 0.521 CP + 1.670 CD + 0.289 CA + 0.757 CB -1.851 V r 2 = 0.986 (9) The coefficients of the regression are similar to those of equation 8, and negative coefficient of the volume variable is meaningful. Table 5 gives the calculated logS w and relative deviations (RD) from equations 5, 7, 8 and 9 as well as the GMRD value.…”

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confidence: 82%

QSPR Modeling using Catalan Solvent and Solute Parameters

Jouyban¹,

Fakhree²,

Shayanfar³

et al. 2011

J. Braz. Chem. Soc.

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A área de correlação quantitativa entre estrutura e propriedade (QSPR) pode beneficiar-se de descritores moleculares que representam interações intermoleculares. Catalan desenvolveu um método de escalas solvatocrômicas para solventes que pode ser explorado para esta finalidade. Neste trabalho, escalas de solvente de Catalan foram usadas como descritores moleculares para o desenvolvimento de modelos QSPR, e para o cálculo de novos descritores de soluto para uso posterior em QSPR. As escalas Catalan para o solvente e os descritores de soluto derivados foram recentemente comparados com o método de descritores de Abraham, em termos da qualidade do QSPR desenvolvido. Os parâmetros Catalan para solventes, que mostraram uma correlação modesta com os correspondentes descritores de Abraham, mostraram-se bem sucedidos para modelar temperatura de fusão, temperatura de ebulição, ponto de ignição, índice de refração, tensão superficial, densidade e parâmetro de solubilidade dos solventes, com médias geométricas dos desvios relativos (GMRD) de 7,1, 6,6, 4,9, 3,8, 9,1, 6,0 e 4,2%, respectivamente. Os descritores do soluto foram obtidos a partir das equações de regressão entre a solubilidade de um soluto em diferentes solventes com um GMRD total de 30,0%. Os descritores de soluto obtidos desta maneira superam o modelo de solvatação geral de Abraham no cálculo de solubilidade em meio aquoso de 27 solutos de várias famílias químicas. Os descritores Catalan podem ser considerados como um recurso valioso para modelagem QSPR.The field of quantitative structure-property relationship (QSPR) can greatly benefit from molecular descriptors that particularly represent the intermolecular interactions. Catalan has developed a set of solvatochromic scales for solvents, which could be exploited for this purpose. In this work, Catalan solvent scales were explored as molecular descriptors for the development of QSPR models, and for the calculation of new solute descriptors for further use in QSPR. Catalan solvent scales and the newly derived solute descriptors were compared with the commonly used set of Abraham descriptors in terms of the quality of the developed QSPRs. Catalan solvent parameters, which showed modest correlation with the corresponding Abraham descriptors, proved to be successful in modeling melting point, boiling point, flash point, refractive index, surface tension, density, and solubility parameter of the solvents with geometric mean relative deviations (GMRD) of 7. 1, 6.6, 4.9, 3.8, 9.1, 6.0, and 4.2%, respectively. The solute descriptors were obtained from regression equations between a solute's solubility in different solvents with an overall GMRD of 30.0%. The solute descriptors obtained in this way outperformed Abraham general solvation model in the calculation of aqueous solubility for 27 solutes of broad chemical ranges. It was concluded that Catalan descriptors can be regarded as a valuable resource for QSPR modeling.Keywords: Catalan, solvatochromic, solubility, modeling, QSPR Jouyban et al. 685 Vol. 22, No. 4, 20...

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“…The solubility of the drug in various solvents was given in 2). The high solubility of candesartan cilexetil in PEG 400 is due to the longer non-polar chain of PEG 400 as the longest non-polar chain reflects the hydrophobic interactions of the drug with the liquid-vehicle molecule [20].…”

Section: Discussionmentioning

confidence: 99%

Effect of Natural and Synthetic Polymers on the Properties of Candesartan Cilexetil Matrix Tablet Prepared by Dry Granulation

Salih

Nief

2016

Asian J Pharm Clin Res

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Objective: The objective of this study is to develop a controlled release matrix tablet of candesartan cilexetil to reduce the frequency of administration, enhance bioavailability and improve patient compliance; a once daily sustained release formulation of candesartan cilexetil is desirable. Methods:The prepared tablets from F1 to F24 were evaluated with different evaluation parameters like weight variation, drug content, friability, hardness, thickness and swelling ability. In vitro release for all formulas were studied depends on the type and amount of each polymer, i.e. (16 mg, 32 mg and 48 mg) respectively beside to the combination effect of polymers on the release of the drug from the tablet. Results:In vitro release showed that formula 13 had the faster release (100% after 4 h) which contained acacia (1:1) and the lowest sustain release was showed for F7 (73% after 8 h) which contained HPMC K100M (1:1). Formula 1 was an 89 % release after 8 h which contain eudragit RS100; F4 was a 100 % release after 5 h which contain Na CMC, F10 was a 100% after 8 h which contain xanthan gum and F16 was a 100 % release after 5 h which contain tragacanth polymer. Formula 9 had a lower release than F7 and F8 respectively. Formula 7 can be used for sustain oral drug delivery of candesartan cilexetil while Formula 13 can be used in contrary as fast release tablets for faster response. Conclusion:Controlled drug delivery system is promising for less dosing and higher patient compliance.

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Estimation of drug solubility in water, PEG 400 and their binary mixtures using the molecular structures of solutes

Cited by 13 publications

References 44 publications

Computational Prediction of Drug Solubility in Lipid Based Formulation Excipients

Computational Prediction of Drug Solubility in Lipid Based Formulation Excipients

QSPR Modeling using Catalan Solvent and Solute Parameters

Effect of Natural and Synthetic Polymers on the Properties of Candesartan Cilexetil Matrix Tablet Prepared by Dry Granulation

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