SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).

The solubilities of three poorly water soluble drugs, phenytoin, diazepam and benzocaine, were measured in various cosolvent-water mixtures. The data were generally described by the relationship: log (S(m)/S(w)) = Σf₁σ₁ where S(m) is the solubility of the drug in the cosolvent-water mixture, S(w) is...

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Main Author: RUBINO, JOSEPH THOMAS.
Language:en
Published: The University of Arizona. 1984
Subjects:
Online Access:http://hdl.handle.net/10150/187780
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spelling ndltd-arizona.edu-oai-arizona.openrepository.com-10150-1877802015-10-23T04:35:02Z SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY). RUBINO, JOSEPH THOMAS. Drugs -- Solubility. Drug carriers (Pharmacy) Phenytoin -- Solubility. Solubilization. The solubilities of three poorly water soluble drugs, phenytoin, diazepam and benzocaine, were measured in various cosolvent-water mixtures. The data were generally described by the relationship: log (S(m)/S(w)) = Σf₁σ₁ where S(m) is the solubility of the drug in the cosolvent-water mixture, S(w) is the solubility of the drug in water, f₁ is the volume fraction of cosolventi and σ₁ is the slope of the log(S(m)/S(w)) vs. f₁ plot. In most cases, some positive or negative deviation from the log-linear solubility equation is observed. The deviation is similar for all three drugs in many of the cosolvent-water mixtures. This suggests that the deviation is primarily due to interactions between the solvent components. However, it could not be predicted from any of the physical properties of the solvent mixtures. Changes in the solute crystal structure could not be identified as a source of nonideality. The deviations from the log-linear solubility equation may involve such factors as changes in solvent structure, hydrophobic hydration, density changes and hydrogen bonding differences between solute and cosolvent. The slopes, σ₁, of the solubilization plots were related to various indexes of solvent polarity including dielectric constant, solubility parameter, partition coefficient, surface tension and interfacial tension. The best correlations were obtained with measures of solvent cohesive forces such as interfacial tension and solubility parameter. In general, the solubilities in mixtures of aprotic cosolvents and water are higher than predicted by any of the polarity indexes. The slopes are thus related to the hydrogen bonding ability of the cosolvent as expressed by the density of proton donor and acceptor groups of the neat cosolvent. The slopes of the solubilization plots can be predicted from linear relationships with polarity indexes of the cosolvent. Therefore it is possible to estimate the slope, σ, in any cosolvent-water mixture from the solubilities in two solvents for a given drug. Furthermore, the solubility in any cosolvent water mixture can be estimated by combining the log-linear solubility equation with the estimated slopes. 1984 text Dissertation-Reproduction (electronic) http://hdl.handle.net/10150/187780 693291463 8424934 en Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. The University of Arizona.
collection NDLTD
language en
sources NDLTD
topic Drugs -- Solubility.
Drug carriers (Pharmacy)
Phenytoin -- Solubility.
Solubilization.
spellingShingle Drugs -- Solubility.
Drug carriers (Pharmacy)
Phenytoin -- Solubility.
Solubilization.
RUBINO, JOSEPH THOMAS.
SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).
description The solubilities of three poorly water soluble drugs, phenytoin, diazepam and benzocaine, were measured in various cosolvent-water mixtures. The data were generally described by the relationship: log (S(m)/S(w)) = Σf₁σ₁ where S(m) is the solubility of the drug in the cosolvent-water mixture, S(w) is the solubility of the drug in water, f₁ is the volume fraction of cosolventi and σ₁ is the slope of the log(S(m)/S(w)) vs. f₁ plot. In most cases, some positive or negative deviation from the log-linear solubility equation is observed. The deviation is similar for all three drugs in many of the cosolvent-water mixtures. This suggests that the deviation is primarily due to interactions between the solvent components. However, it could not be predicted from any of the physical properties of the solvent mixtures. Changes in the solute crystal structure could not be identified as a source of nonideality. The deviations from the log-linear solubility equation may involve such factors as changes in solvent structure, hydrophobic hydration, density changes and hydrogen bonding differences between solute and cosolvent. The slopes, σ₁, of the solubilization plots were related to various indexes of solvent polarity including dielectric constant, solubility parameter, partition coefficient, surface tension and interfacial tension. The best correlations were obtained with measures of solvent cohesive forces such as interfacial tension and solubility parameter. In general, the solubilities in mixtures of aprotic cosolvents and water are higher than predicted by any of the polarity indexes. The slopes are thus related to the hydrogen bonding ability of the cosolvent as expressed by the density of proton donor and acceptor groups of the neat cosolvent. The slopes of the solubilization plots can be predicted from linear relationships with polarity indexes of the cosolvent. Therefore it is possible to estimate the slope, σ, in any cosolvent-water mixture from the solubilities in two solvents for a given drug. Furthermore, the solubility in any cosolvent water mixture can be estimated by combining the log-linear solubility equation with the estimated slopes.
author RUBINO, JOSEPH THOMAS.
author_facet RUBINO, JOSEPH THOMAS.
author_sort RUBINO, JOSEPH THOMAS.
title SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).
title_short SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).
title_full SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).
title_fullStr SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).
title_full_unstemmed SOLUBILIZATION OF SOME POORLY SOLUBLE DRUGS BY COSOLVENTS (FORMULATION, IDEALITY, POLARITY).
title_sort solubilization of some poorly soluble drugs by cosolvents (formulation, ideality, polarity).
publisher The University of Arizona.
publishDate 1984
url http://hdl.handle.net/10150/187780
work_keys_str_mv AT rubinojosephthomas solubilizationofsomepoorlysolubledrugsbycosolventsformulationidealitypolarity
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