Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility

Patel, Shruti V.; Patel, Sarsvatkumar

doi:10.1016/j.ejps.2015.06.014

Cited by 33 publications

(10 citation statements)

References 53 publications

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“…The loading capacity of the formulations ranged from 1.7 mg/g to 93.0 mg/g in type II, 1.3 mg/g to 167.1 mg/g in type IIIA, 2.8 mg/g to 166.0 mg/g in type IIIB, and 1.9 mg/g to 92.9 mg/g in type IV. This extensive data set confirms earlier studies, 16 − 18 i.e., the total loading capacity of a complex formulation can be calculated by proportionately summing up the solubility of the compound in the single excipients ( eq 1 ). This trend was regardless of formulation type or whether the compound displayed low, medium, or high solubility in the LBFs ( R 2 0.91) ( Figure 4 A).…”

Section: Resultssupporting

confidence: 87%

“… 14 , 15 Recent studies on lipid systems have used similar approaches to estimate drug solubility in complex lipid mixtures. 16 − 18 Based on four model compounds, it was shown that the sum of the loading capacity in the LBF is equal to the solubility of each included excipient, when compensated for the fraction of the excipient in the formulation. 17 The weakness of this methodology is that it requires experimental measurements, which limits the applicability for rapid estimation of LBF loading capacity.…”

Section: Introductionmentioning

confidence: 99%

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Tools for Early Prediction of Drug Loading in Lipid-Based Formulations

2015

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Identification of the usefulness of lipid-based formulations (LBFs) for delivery of poorly water-soluble drugs is at date mainly experimentally based. In this work we used a diverse drug data set, and more than 2,000 solubility measurements to develop experimental and computational tools to predict the loading capacity of LBFs. Computational models were developed to enable in silico prediction of solubility, and hence drug loading capacity, in the LBFs. Drug solubility in mixed mono-, di-, triglycerides (Maisine 35-1 and Capmul MCM EP) correlated (R2 0.89) as well as the drug solubility in Carbitol and other ethoxylated excipients (PEG400, R2 0.85; Polysorbate 80, R2 0.90; Cremophor EL, R2 0.93). A melting point below 150 °C was observed to result in a reasonable solubility in the glycerides. The loading capacity in LBFs was accurately calculated from solubility data in single excipients (R2 0.91). In silico models, without the demand of experimentally determined solubility, also gave good predictions of the loading capacity in these complex formulations (R2 0.79). The framework established here gives a better understanding of drug solubility in single excipients and of LBF loading capacity. The large data set studied revealed that experimental screening efforts can be rationalized by solubility measurements in key excipients or from solid state information. For the first time it was shown that loading capacity in complex formulations can be accurately predicted using molecular information extracted from calculated descriptors and thermal properties of the crystalline drug.

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Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Tools for Early Prediction of Drug Loading in Lipid-Based Formulations

2015

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“…This log-linear model describes the exponential increase in the solubility of non-polar drugs (on a log scale) with the linear increase in cosolvent concentration [ 33 , 34 ]. Recent studies of lipid systems have used this theory to estimate drug solubility in complex lipid mixtures [ 35 – 37 ]. One of the weaknesses of this methodology is the requirement for experimental measurements, which limits their applicability for rapid estimation of solubility.…”

Section: Computational Tools For Addressing Drug Loading and Formulatmentioning

confidence: 99%

Models for Predicting Drug Absorption From Oral Lipid-Based Formulations

Alskär

Bergström

2015

Curr Mol Bio Rep

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In this review, we describe the in vitro tools currently used to identify when a lipid-based formulation has the potential to deliver a poorly water-soluble drug via the oral route. We describe the extent to which these tools reflect the in vivo performance of the formulation and, more importantly, we present strategies that we foresee will improve the in vitro-in vivo correlations. We also present emerging computational methods that are likely to allow large parts of the formulation development to be carried out in the computer rather than in the test tube. We suggest that these computational tools will also improve the mechanistic understanding of in vivo formulation performance in the complex and dynamic environment of the gut.

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“…The knowledge of the solubility of materials in different solvents and solvent mixtures has great significance for many applications [1][2][3][4][5]. Numerous methods can provide a reliable solution for this problem.…”

Section: Introductionmentioning

confidence: 99%

Solubility Determination of Hydroquinone in Dichloromethane, Trichloromethane and Carbon Tetrachloride by Using the Co-solvent Calibration Method

Kiss

Kunsági‐Máté

2019

J Solution Chem

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In this report, the solubility of hydroquinone (1,4-dihydroxybenzene) was determined in dichloromethane, trichloromethane and carbon tetrachloride at 298 K by using cyclic voltammetry. By the proposed cosolvent calibration method a mixed solvent was used for the determination of solubility where acetonitrile was the co-solvent. The molar ratios of the two solvents were uniform during the whole procedure both in the calibration solutions and in solutions used for solubility determinations. The solubility of hydroquinone decreased by the decrease of solvent permittivity, which were in dichloromethane 5.683 mmol•L −1 , in trichloromethane 2.785 mmol•L −1 and in carbon tetrachloride 0.321 mmol•L −1 .

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Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility

Cited by 33 publications

References 53 publications

Tools for Early Prediction of Drug Loading in Lipid-Based Formulations

Tools for Early Prediction of Drug Loading in Lipid-Based Formulations

Models for Predicting Drug Absorption From Oral Lipid-Based Formulations

Solubility Determination of Hydroquinone in Dichloromethane, Trichloromethane and Carbon Tetrachloride by Using the Co-solvent Calibration Method

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