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Biomedical subjects

J H Collett

Publications and source records attributed to J H Collett.

At least 37 records · Page 2Linked to original sources
PubMed1995

Solubilisation of drugs in micellar systems studied by eluent gel permeation chromatography.

PURPOSE: The purpose of the study was to investigate the potential of a chromatographic method which is based on elution gel chromatography (EGPC) in the study of solubilisation of drugs in micellar solutions. METHODS: The EGPC method differs from conventional GPC in the use of a solution of the associating surfactant as eluent (rather than solvent) and the injection of a small volume of solution of different concentration (or alternatively injection of solvent alone) to probe the association equilibrium in the eluent. The technique was applied to a study of the solubilisation of selected drugs in aqueous micellar solutions of a triblock copolymer (Synperonic-PE F127) composed of oxyethylene [E, OCH2CH2] and oxypropylene [P, OCH2CH(CH3)] units with nominal molecular formula E98P67E98. RESULTS: EGPC curves were obtained showing vacancy peaks at the elution volumes of the drugs, clearly demonstrating their solubilisation. In addition, the micelle-molecule equilibrium of the copolymer surfactant could be monitored at all times. Quantitative determination of the partition of solute between micelles and solvent phase was not possible due to the incomplete conversion of molecules to micelles in solutions of the selected copolymer. CONCLUSIONS: The EGPC technique provides evidence for the solubilisation of the drugs in aqueous solutions of Synperonic F127; a more thorough assessment of its potential for quantitative measurement of solubilisation requires the use of a surfactant which is wholly (or at least mainly) in the micellar state under the conditions of use.

Adsorption↗
PubMed1995

The release of 5-fluorouracil from a swellable matrix of a triblock copolymer of epsilon-caprolactone and ethylene oxide.

PURPOSE: The purpose of this study was to investigate the influence of hydration characteristics on the in vitro release of 5-fluorouracil from a swellable matrix prepared using a novel triblock copolymer of poly(epsilon-caprolactone) and poly(oxyethylene). METHODS: Matrices were prepared by dry compression of mixtures of the drug and copolymer using low compressional forces. Release studies were performed using a custom made rotating basket dissolution apparatus. The positions of the eroding and swelling fronts within the matrices during hydration were monitored using freeze fracture scanning electron microscopy. RESULTS: Analysis of the release data revealed a predominantly diffusion controlled mechanism. Observations of the swelling characteristics of the copolymer matrices on immersion in Sørensen's buffer at pH 7.4 revealed gel formation and preferential swelling in the radial direction with visible erosion of the matrix after 4h. During hydration, a gradual increase in gel layer thickness was noted prior to the erosion and eventual dissolution of the matrix. CONCLUSIONS: This study demonstrates a means of differentiating the relative importance of the swelling characteristics in determining the release mechanism and subsequent release rate from swellable matrices.

Antimetabolites, Antineoplastic↗
PubMed1987

The influence of the ammonium ion on the stability of ethacrynic acid in aqueous solution.

Investigations by reversed-phase HPLC into the stability of ethacrynic acid in buffered aqueous solutions containing either sodium or ammonium ions showed that the extent of degradation was influenced both by the species and concentration of the cation. A reported incompatibility between ethacrynic acid and the ammonium ion, attributed to the influence of the ammonium ion on an equilibrium existing between ethacrynic acid and one of its known degradation products, was shown to be due to the generation of an additional degradation product in ammonium-containing solutions only. This product was isolated and identified. Different pathways of degradation were shown to be operative in sodium- and ammonium-containing solutions. The addition of formaldehyde or a formaldehyde scavenger (hydroxyammonium chloride) was found to influence the rate of loss of ethacrynic acid, but the decomposition products provided no evidence for the existence of the reported equilibrium.

Journal Article↗
PubMed1985

Liquid chromatographic analysis of ethacrynic acid and degradation products in pharmaceutical systems.

An accurate, reproducible, and specific reversed-phase high-performance liquid chromatographic (HPLC) system was developed for the determination of ethacrynic acid and its degradation products. The method was used in stability studies of the drug in the solid state, in solution, and in dosage forms. Three degradation products were isolated by preparative chromatography and identified by several techniques, principally NMR and MS. TLC Rt and HPLC response factors are quoted. A degradation scheme consistent with the observed stability profiles is proposed.

Chemistry, Pharmaceutical↗
PubMed1982

The influence of gel formulation on the diffusion of salicylic acid in polyHEMA hydrogels.

The influence of solute concentration, gel hydration, and crosslinking density on diffusion rates in polyHEMA hydrogels has been investigated using a radio-tracer technique. At hydrations above 31% water, diffusion is by pore flow, and increases in the crosslinking density of gels bring about a decrease in the diffusion coefficient, D. Below 31% hydration, diffusion is predominantly by solution diffusion and changes in crosslinking density have little effect on the diffusion coefficient. The diffusion coefficient is invariant with solute concentration within the range reported, although a very high solute concentration, for the gels of lower hydration, the diffusion coefficient is higher than expected. A high value for D may be due to saturation of the binding sites of the diffusant on the polymer chains, leaving a greater proportion of diffusant available for transport.

Diffusion↗
PubMed1980

Rate constants for drug release from micellar solutions of non-ionic surfactants.

The release of weak acid from micellar solutions containing different concentrations of two structurally related non-ionic surfactants was estimated using a dynamic dialysis apparatus. In all cases the effect of the surfactant was to reduce the amount of weak acid transferred. The data have been subjected to compartmental analysis using non-linear regression analysis. Rate constants for exchange cross the dialysis membrane were independent of surfactant concentration. As surfactant concentration increased the rate constants for transfer from the non-micellar region did not show a marked change.

Kinetics↗
PubMed1979

Relationships between poloxamer structure and the solubilization of some para-substituted acetanilides.

Saturation solubilities of several para-substituted acetanilides have been measured at 37 degrees C in aqueous solutions of structurally related polyoxyethylene-polyoxypropylene block copolymers-poloxamers L62, L63, L64, P65 and F68. These poloxamers differ only in the amount of ethylene oxide in the hydrophil. Solubilities increased with increasing poloxamer concentration. As the oxyethylene chain length of the poloxamer increased, then the solubilizing capacity per equivalent of oxyethylene decreased. The moles of acetanilide derivative solubilized per mole of poloxamer increased with poloxamer oxyethylene content in the case of the less hydrophobic acetanilides but was invariant in the more hydrophobic ones. The solubilizing capacities have been discussed in terms of the inter-relationships between the hydrophobic nature of the solubilizate and solubilizer and the site of solubilization on the poloxamer molecule.

Acetanilides↗
PubMed1979

Biological effectiveness, in goldfish, of some p-substituted acetanilides alone and in the presence of poloxamers.

The death times of goldfish have been measured in aqueous solutions containing different concentrations of p-substituted acetanilides alone or in the presence of poloxamers. Plots of reciprocal death time versus concentration were linear with a positive concentration intercept, the minimum effective concentration (MEC). The MEC values were directly related to the pi value (hydrophobic-lipophilic constant) of the functional group on the acetanilide indicating that activity is directly related to lipophilicity. Slopes of reciprocal death time versus drug concentration were linearly related to pi values but there was no direct dependence. The presence of poloxamers in aqueous acetanilide solutions reduced the goldfish death time. The effect of the poloxamers is believed to be one of rendering the goldfish membrane more permeable to drugs.

Acetanilides↗
PubMed1976

Correlations between substituent parameters of 4-substituted benzoic acids and their in vitro dissolution and partitioning.

The in vitro dissolution and partitioning of some 4-substituted benzoic acids from nondisintegrating disks was investigated using a water-octanol system. The rates of appearance of benzoic acids in the aqueous phase differed from the rates of appearance in octanol, probably due to back-transfer from the octanol phase. The suitability of the procedure for investigating the influence of molecular modification on in vitro dissolution and partitioning is considered. Correlations among the rates of appearance in octanol, the rates of appearance in an aqueous phase, and substituent parameters of benzoic acids were investigated. The best statistical fit was obtained using molecular orbital substituent indexes.

Benzoates↗
PubMed1976

Some effects of urea on drug dissolution.

Solubilities and dissolution rates of salicylic acid have been determined in urea solutions at different pH values. Solubilities increased with pH and urea concentration; a solubilization mechanism was considered to be operating. The solubilization effect of urea was greatest on the non-ionzed moieties of the solute. Dissolution rates of salicylic acid increased with pH and urea concentration. The increase in dissolution rate paralleled increases in solubility. The role of solubilizing effect in the enhancement of dissolution rate by urea is discussed.

Hydrogen-Ion Concentration↗
PubMed1976

Some factors influencing dissolution from salicylic acid-urea solid dispersions.

Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained.

Calorimetry↗