P. H. Elworthy

The influence of solution viscosity on the dissolution rate of soluble salts, and the measurement of an “effective” viscosity

The rate of solution of KCl and NaCl from compressed discs has been determined under controlled conditions, in water at 25° and in solutions of varying concentrations of polyvinylpyrrolidone (molecular weight 360 000), polyoxyethylene glycol 6000 and cetomacrogol 1000. Dissolution rate constants decrease with increasing bulk solution viscosity, as expected, but no one equation relating rate constant and bulk viscosity fits the results for the systems studied. Calculation of an effective viscosity from the diffusion coefficients of the salts in water and the diffusion coefficients of the salt in the polymer solutions enables an empirical correlation of the results to be made. The relation of the effective viscosity to the microscopic viscosity is discussed in an Appendix.

Identification of the site of solubilization of various compounds by cetomacrogol

Solubilization of some of the esters of p‐hydroxybenzoic acid by cetomacrogol 1000 solutions has been investigated by ultraviolet spectrophotometry, nuclear magnetic resonance spectrometry and viscometry to provide evidence on the environment of each part of the solubilizate molecule as well as the detergent molecule. Hydration of the micelles calculated from the viscometry results, gave further evidence on the site of solubilization of the compounds. On the basis of these results and solubility results published previously it is suggested that the compounds are solubilized as follows: p‐Hydroxybenzoic acid is wholly solubilized deep in the oxyethylene layer of the micelle. Ethyl p‐hydroxybenzoate is solubilized mostly in the oxyethylene layer and is situated adjacent to the core: some solubilization occurs within the core. Butyl p‐hydroxybenzoate is solubilized mainly at the oxyethylene‐hydrocarbon junction, the phenyl ring in the oxyethylene layer and the butyl chain in the core: some solubilizate is wholly present in the core. Methyl p‐methoxybenzoate: most of the compound is dissolved in the micellar core, but some is also present in the oxyethylene layer. Benzene is solubilized in a similar manner to methyl p‐methoxybenzoate.

Solubilization of griseofulvin by nonionic surfactants

Four nonionic surfactants, Me[CH2]15·[OCH2·CH2]xOH where x = 10, 22, 45 and 60, and polyoxyethylene glycols 200, 400 and 1000 increased the solubility of griseofulvin over its value in water. Cetomacrogol micelles solubilize two molecules of griseofulvin per micelle. The site of solubilization seems likely to be the polyoxyethylene part of the micelles. The partial molal heats and entropies of solution decrease as surfactant or polyoxyethylene glycol concentration is increased.

The solubility of sulphadiazine in water‐dimethylformamide mixtures

Precise measurements of the solubility of sulphadiazine in water, dimethylformamide (DMF), and a range of mixtures of these solvents have been made at 20°, 30°, and 40°. The solubility of sulphadiazine in the mixtures increases with their DMF content. The partial molar heats and entropies of solution decrease with increasing DMF concentration.

A note on the solubility of griseofulvin

The solubility of griseofulvin in heptane, water and benzene over the temperature range 15–45° is reported together with the thermodynamic properties for solution of the antibiotic in these solvents.

The effect of some non‐ionic surfactants and a polyoxyethylene glycol on the dissolution rate of griseofulvin

Measurements of the dissolution rate of griseofulvin in water, four non‐ionic surfactants, and a polyoxyethylene glycol have been made. These results are analysed in terms of a zero order rate constant (k1) for transfer of the drug from the crystal to the bulk of the solution, and a first order constant (k2) for the reverse process. Surfactants greatly increase the dissolution rate, increasing k1 and decreasing k2. Polyoxyethylene glycol is not so effective as the surfactants at increasing dissolution rates. In an attempt to interpret k1 and k2, it appears that both chemical and transport processes are involved in the dissolution, the presence of surfactant decreasing the energy change for transferring griseofulvin molecules from the crystal to the solution.

The physical chemistry of some non-ionic detergents*

HE physical chemistry of non-ionic detergents, in particular their T surface activity and micellar properties in aqueous solution, has received much attention. In this review the physical chemistry of polyoxyethylene-ether detergents of the type Me.[CH,]y.[OCH,CH,]x.OH is outlined. For convenience, the formulae are abbreviated in the style thus : Dodecyl-n, for Me~[CH,],,~[OCH,CH,],~OH, n representing the ethylene oxide unit. Non-ionic detergents do not ionise in aqueous solution, and thus have many advantagcs both in detergent properties and for chemical studies. Furthermore, a range of compounds with a constant hydrophobic portion, but a varying hydrophilic moiety, can be obtained without fundamentally altering the chemical structure of the detergent, enabling a fuller and more comprehensive study to be made than is possible in an ionic series where the hydrophilic portion can be altered only by changing the ion. Although polymers of ethylene oxide of up to six units were first synthesised over 100 years ago, it was not until around 1930 that their commercial potential, and particularly that of their derivatives, was realised. Since then wide ranges of compounds incorporating the polyoxyethylene glycols have been produced for a multitude of purposes, ranging from aids in drilling to pharmaceutical preparations, where their wetting, foaming, dispersing, or emulsifying properties are utilised. In the study of non-ionic detergents the most important experimental methods used have been those described below. BSc., Ph.D., M.P.S.

Stabilization of oil-in-water emulsions by non-ionic detergents: the effect of polyoxyethylene chain length

The stability of emulsions of anisole and chlorobenzene in water has been estimated by following microscopically the size distribution of emulsions as a function of time. The effect of increasing the length of the polyoxyethylene glycol chain of the hexadecyl ether non‐ionic stabilizers from three units to nine units was determined. Electrophoretic measurements indicated that the higher stability obtained on increasing the glycol chain length is not due to an increasing surface potential: it is ascribed to an entropic effect. Stability data are tabulated as rates of coalescence (s−1) and results are presented relating these rates to zeta‐potential, surface concentration and polyoxyethylene chain length. The results are discussed qualitatively and compared with the results obtained with cetomacrogol 1000 (Elworthy & Florence, J. Pharm. Pharmac., 1967, 19, 140S).

Stabilization of oil-in-water emulsions by non-ionic detergents: electrical and entropic contributions to stability.

Calculations of the attractive and repulsive forces between globules of anisole and chlorobenzene in the presence of non‐ionic detergents of varying polyoxyethylene chain length are presented. The equations of the Derjaguin‐Landau‐Verwey‐Overbeek theory are used and the effect on the attractive potential of the adsorption of stabilizer onto the particle is taken into account. The adsorbed film was found to increase the attractive forces between the particles, VA. In the previous paper (Elworthy & Florence, J. Pharm. Pharmac., 1969, 21, 70) it was shown that the electrical contribution to stability is a secondary stabilizing factor. More quantitative estimates of this contribution have been made. The entropic repulsion has been calculated using an equation of Ottewill & Walker. The energy‐distance diagrams are discussed in the light of the experimental results presented in the previous paper.

Membrane osmometry of solubilized systems

The solubilization of decane, ethyl p‐hydroxybenzoate, methyl anisate and p‐hydroxybenzoic acid by aqueous micellar solutions of cetomacrogol 1000 has been examined by membrane osmometry and viscosity techniques. The effect of the solubilizates on the number‐average micellar molecular weight, Mn, has been related to their site of incorporation in the micelle. Decane and methyl anisate are solubilized in the hydrocarbon core of the micelles and both compounds produce an increase in Mn up to a maximum value of 2·0 times 105, at a solubilizate concentration of approximately 80% of the saturation limit for each compound. This increase is shown to result from an increase in the number of molecules of both solubilizate and of surfactant per micelle. Further addition of solubilizate, to produce a saturation level in excess of 80%, results in a decrease in micellar size in both systems. The solubilization of ethyl p‐hydroxybenzoate and p‐hydroxybenzoic acid is thought to involve the oxyethylene region of the micelle and both solubilizates cause an increase in Mn owing to the inclusion of solubilizate into the micelle, the number of molecules of surfactant per micelle being unaffected by the solubilization process. Viscosity studies on the decane‐ceto‐macrogol‐water system are interpreted as indicating no change in either micellar symmetry or hydration as a result of solubilization. A spherical model for the micelles is shown to be consistent with the experimental data.