PubMed Health⌕ Search

Biomedical subjects

G Buckton

Publications and source records attributed to G Buckton.

At least 37 records · Page 2Linked to original sources
PubMed1999

Assessment of disorder in crystalline powders--a review of analytical techniques and their application.

The need to be able to measure amorphous contents in crystalline powders is now recognised. In this review, calorimetric and gravimetric methods are reviewed in a way that should alert workers in the field to the theoretical, and practical considerations which are important to understanding how best to study crystalline samples which contain low levels of amorphous material. It is shown that vapour sorption techniques are very powerful as long as serious consideration is given to the choice of environmental conditions and the exact experimental methodology. As the amount of published work in this field grows, it becomes increasingly necessary to describe experimental and data manipulation methods in great detail.

Calorimetry↗
PubMed1999

Differences in crystallization behavior between quenched and ground amorphous ursodeoxycholic acid.

PURPOSE: To study the crystallization of ground and quenched ursodeoxycholic acid (UDCA) and to characterize their amorphous states. METHODS: Amorphous UDCA was prepared by grinding and also by rapid cooling of the melt. These samples were characterized by powder X-ray diffraction (XRD), near IR spectra and dynamic water sorption. The heat associated with crystallization was measured in an isothermal microcalorimeter at 25 degrees C at various relative humidities (RH) (50%-100%) and, in the presence of the vapour from a mixed solvent of ethanol and water (ethanol conc. 10%-100%). The specific surface area was calculated from krypton adsorption. Contact angles were measured by using a Wilhelmy plate to calculate the surface energy of the samples. RESULTS: Ground and quenched samples yielded amorphous XRD patterns. Differential scanning calorimetry thermographs of the milled sample revealed that crystallization occurred at around 80 degrees C, whereas the quenched sample did not crystallize. Exposure to humid air did not result in crystallization of either amorphous sample during the microcalorimetric experiments. In the presence of ethanol vapour, the ground sample did, but the quenched sample did not, crystallize. The amount of water sorption into the quenched sample was larger than that of the ground sample at low RH. The surface energy of the quenched material was different to that of the ground. Peak shifts were observed in the NIR spectra at around 1450, 2100 nm, allowing differentiation between the ground and quenched samples. CONCLUSIONS: It can be concluded that different molecular states of amorphous UDCA were obtained depending on the preparation method. The crystallisation of amorphous UDCA was related to the molecular state of disorder.

Crystallization↗
PubMed1998

Crystallization of bulk samples of partially amorphous spray-dried lactose.

The crystallization of partially amorphous spray-dried lactose was studied as a function of sample size. Crystallization occurred gradually over a period of 80 hr for a 95-g sample. The water content during crystallization was lower than that needed to cause crystallization if it had been distributed evenly throughout the bed, thus the absorbed water must have been unevenly distributed. The weight of the sample continued to change for days after crystallization was completed, because of the slow desorption of condensed water and the very slow formation of the hydrate form. Surprisingly, all samples with a weight between 42 and 95 g were found to take up the same mass (not percent) of water at the same time. This provides further evidence that the water was not evenly distributed throughout the sample. Water loss after this peak differed in the different weight samples, with the largest weights resulting in the lowest residual weight after 2 weeks. Only the sample of 22 g load had a different peak weight and a much lower weight loss after crystallization. This study provides detail of how partially amorphous bulk samples crystallize.

Calorimetry↗
PubMed1997

Characterisation of small changes in the physical properties of powders of significance for dry powder inhaler formulations.

In this paper we address the following issue: Why is surface characterisation important? All pharmaceutical processes (with the exception of mixing two gasses) involve interfacial contact, and, consequently, it is not surprising that surface energetics play an important role in determining the outcome of all events. For a dry powder inhaler system interfacial considerations may relate to drug-drug interactions (cohesion), drug-carrier or drug-device interactions (adhesion) and deaggregation phenomena during use. As all adhesive and cohesive interactions are interfacial phenomena it is reasonable to accept that the basis of interactions within dry powder inhalers is through interfacial forces, which can be divided into apolar (Lifshitz-van der Waals) and polar (electron donor-electron acceptor) components. Further to this it can be accepted that changes in the nature of any surface within the product (the drug, the carrier or the container) can be expected to result in changes in the surface interactions involving that phase. Thus, in essence, the success or failure of a formulated inhalation device is dependent upon the nature of the surface of the materials used, and, as such, measurement of these surfaces becomes of paramount importance. In this review comparatively little effort will be taken to prove the dominant role of surface energetics in inhalation products; this is primarily because much of the proof which exists is held as confidential by manufacturers. Consequently, this review will concentrate on surface characterisation of powders with respect to determination of surface energies and changes in solid-state properties.

Journal Article↗
PubMed1997

Differences between dynamic and equilibrium surface tension of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymer surfactants (poloxamers P407, P237, and P338) in aqueous solution.

Poloxamer surfactants are macromolecules with complex interfacial behavior. Although a number of studies of equilibrium surface tension have been published recently, there is little information on the diffusion of these large molecules to the air-liquid interface. Because most surfactants are used in dynamic systems, the diffusion to the surface can be critical in controlling performance. In this study a maximum bubble pressure method was used to study dynamic surface tension (DST) of Poloxamer P407, P237, and P338, at a range of bubble rates (surface age) and concentrations, at either 25 or 35 degrees C. The DST did not change at the critical micelle concentration and also did not vary in the same manner as the equilibrium surface tension (EST) with respect to temperature. It was concluded that DST behavior of the surfactants was most closely related to the poly(oxyethylene) content and/or total molecular weight of the surfactants, whereas the micellization and hence the EST were more closely related to the poly(oxypropylene) content.

Poloxalene↗
PubMed1996

Dissolution behaviour of sulphonamides into sodium dodecyl sulfate micelles: a thermodynamic approach.

The surface energies of four sulfonamides have been assessed from contact angle data, using the Lewis acid-base approach. From these data the free energy of adhesion between the drugs and sodium dodecyl sulfate (SDS) head groups and tails has been calculated. The most favored interaction was for adhesion to the SDS tails, rather than the head groups. The initial rotating disk dissolution rate (hereafter termed dissolution rate) of drug compacts has been measured in water and water with SDS micelles at a range of temperatures. The thermodynamic parameters of activation have been calculated from the rate data. Linear relationships exist between the enthalpy of transfer between water and SDS micelles and the free energy of adhesion between the drugs and both SDS head groups and SDS tails. The most nonpolar drugs had the most favored free energy of adhesion and the most favored enthalpy of transfer. The most polar drug had a disfavoured free energy of adhesion to the SDS head and a disfavoured enthalpy of transfer. This response demonstrates that the most important barrier to the passage from the aqueous fluid to the hydrophobic core of the micelle is the monopolar repulsion between the polar forces of the drug and head group surface energies. This provides a new insight into a possible mechanism of solubilization and offers the prospect of understanding even more complex partitioning behavior.

Chemical Phenomena↗
PubMed1996

The effect of temperature on the surface nature of an adsorbed layer of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers.

PURPOSE: To investigate the influence of the temperature at which adsorption takes place and the temperature at which the adsorbed surface is studied on the polarity of Poloxamer adsorbed to a hydrophobic surface. The implication is that changes in surface nature of adsorbed Poloxamer may subsequently be related to functionality, such as changes in opsonisation of Poloxamer coated latex in animals. METHODS: The surface energies of Poloxamer surfactant have been calculated following adsorption to silanised glass plates. The adsorption to the plates was undertaken at a range of concentrations and at different controlled temperatures. The contact angles were measured using three different liquids on each surface, at a range of controlled temperatures. The surface energies were calculated using the harmonic mean and the acid-base models, via Wilhelmy plate contact angle measurements. These data were compared with previously published adsorption and hydrophobic interaction chromatography studies. RESULTS: The apolar surface energy term remained consistent, but the polar contribution (which was totally of the electron donor type) changed depending upon the temperature of adsorption (and to a lesser extent the temperature at which the surface energy was measured). The polar nature was most elevated at the critical micelle concentration/temperature. The data are consistent with estimates of surface hydrophobicity made using hydrophobic interaction chromatography. CONCLUSIONS: It is argued that the changes in surface energy, which result from the different adsorption conditions, can be expected to influence the functionality of the adsorbed coat, especially for application such as drug targeting.

Adsorption↗
PubMed1995

A microcalorimetric investigation of the interaction of surfactants with crystalline and partially crystalline salbutamol sulphate in a model inhalation aerosol system.

PURPOSE: The purpose of the work is to study the adsorption of Oleic acid and Span 85 (materials frequently used in aerosols as surfactants) onto partially amorphous and essentially crystalline salbutamol sulphate, attempting to understand the behaviour of metered dose inhalers (MDIs) and observing whether there were any differences in adsorption behaviour and if this could be related to the surface properties of the powder. METHODS: Isothermal titration microcalorimetry was the principal technique used to measure the adsorption behaviour of surfactants to salbutamol sulphate. A Malvern particle size analyzer was also employed to provide size data on the interactions between the surfactant and powder suspensions. RESULTS: The calorimetric data revealed that surfactant adsorption to the crystalline micronised powder (78% RH and aged dry sample) produced significant exotherms, whereas adsorption to the partially amorphous micronised powder resulted in small heat responses. The differences in adsorption behaviour to the partially crystalline and crystalline surfaces resulted in changes in aggregation behaviour. CONCLUSIONS: The stability of MDIs varies depending on the water content, crystallinity and surface composition of the powder. The advantages of using isothermal titration microcalorimetry to evaluate this surface behaviour in such difficult systems was demonstrated.

Administration, Inhalation↗
PubMed1995

Development of a flow microcalorimetry method for the assessment of surface properties of powders.

PURPOSE: This study describes the development of a microcalorimetric flow cell which allows powder surface energetics to be probed my means of measuring their interaction with water vapour. METHODS: A flow cell has been constructed and tested in an isothermal microcalorimeter to assess the interaction between water vapour and powder surfaces. The cell was constructed to mix two separate air streams (0% and 100% relative humidity respectively) to create any humidity at a standard flow rate. The powder sample was equilibrated in dry air and then exposed to sequential increments in humidity. RESULTS: Adsorption isotherms were constructed from the cumulative heat as a function of humidity. It was possible to differentiate between different samples of alpha-lactose monohydrate (which appeared identical by contact angle determination). It was also possible to measure adsorption to two different alkyl p-hydroxybenzoates which were hydrophobic and of low surface area. CONCLUSIONS: This technique offers a very sensitive and versatile method of obtaining a reliable indication of powder surface energetics and as such is a major advance in the field.

Benzoates↗
PubMed1995

Modelling mucoadhesion by use of surface energy terms obtained from the Lewis acid-Lewis base approach. II. Studies on anionic, cationic, and unionisable polymers.

Surface energies of carbopol, chitosan, hydroxypropyl cellulose (HPC) and poly(HEMA) were assessed from contact angle and surface tension experiments. The surface energy was considered in terms of an apolar Lifshitz-van der Waals term and a polar acid-base term, which in turn is divided into electron donor and electron receptor (Lewis acid-Lewis base) contributions. Using these surface energy terms the interaction of dry and hydrated polymer with mucin in the presence of either artificial gastric or intestinal fluid, or saline was predicted. The predictions were related to measured forces of detachment. There was a significant difference between the surface energy on dry and hydrated HPC and also for carbopol; for the other polymers either the surface energy of the hydrated material was not detectable, or the effect of hydration was minimal. There were good correlations between mucoadhesive strength and the calculated free energies of interaction between mucin and polymer in the presence of each of the fluids, for each individual polymer. Thus, two trends were observed, one for unionisable and the other for ionisable polymers. It is argued that the increased mucoadhesion seen with ionisable polymers (compared with the predicted value based on results of unionisable polymers) is a direct result of the ionic interaction. No attempt has been made to correct for the ionisation effect, but the surface energy predictions provide insight into the mechanism of the mucoadhesion process. This approach is useful for understanding and predicting interactions between different materials and biological components.

Acid-Base Equilibrium↗
PubMed1994

The interaction of albumin and drugs with two haemofiltration membranes.

The sorption of phenobarbitone sodium, barbitone sodium and fluconazole onto haemofiltration membranes made from polysulphone or a co-polymer of polyamide and polyvinylpyrrolidone was investigated in the presence and absence of albumin. The sorption of albumin was also followed in the presence of phosphate-buffered saline. Drug binding to the membrane was found to be reversible. Knowledge of the lipophilicity of the drug and hydrophobic/hydrophilic nature of the membrane did not allow successful prediction of the extent of binding of all the drugs; nor did knowledge of the extent of ionization of the drug and the charge of the membrane. Albumin bound to the polysulphone membrane in a manner that suggested the surface area to which it was binding was around 10 times greater than reported. In the presence of albumin there was a larger coefficient of variation in the binding of drugs to both membranes. The presence of albumin significantly decreased the binding of fluconazole, but not the other drugs, to the polysulphone membrane; however, albumin had no effect on the binding of any of these drugs to the polyamide membrane. We conclude that the binding of drugs to haemofiltration membranes cannot be simply predicted from knowledge of the hydrophilic/hydrophobic nature or charge of the drug and membrane, nor from the protein binding of the drug.

Barbital↗
PubMed1992

Safety aspects of non-ionic surfactant vesicles: a toxicity study related to the physicochemical characteristics of non-ionic surfactants.

Two different toxicity models were used to assess the relationship between the physicochemical properties of non-ionic surfactant vesicles (NSVs), and the safety of these vesicles for topical drug administration. The vesicles used in this study consisted of polyoxyethylene alkyl ethers (CnEOm) in which the number of C atoms (n) varied between 12 and 18 and the number of oxyethylene units (m) between 3 and 7. The physicochemical properties of the vesicles are described in terms of hydrophilic-lipophilic balance (HLB) values, and critical micelle concentrations (CMC), and the rigidity of the bilayers as determined by the gel-liquid transition temperatures and the cholesterol content of the bilayers. The first toxicity model, comprising the measurement of the ciliary beat frequency, is a tool to assess the safety of intranasally applied formulations. Studies using this ciliotoxicity model revealed that by increasing the length of the alkyl chain of the surfactant, a decrease in toxicity was observed. The opposite correlation was found if the length of the polyoxyethylene headgroup was increased. Furthermore, it was observed that gel-state vesicles produce less of an effect on the ciliary beat frequency than liquid state vesicles. The second toxicity model, comprising the determination of cell proliferation of human keratinocytes, is a method to assess skin irritancy. In contrast to the ciliotoxicity model the length of the polyoxyethylene headgroup and of the alkyl chains did not seem to have an effect on the safety of the vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1986

A vacuum microbalance technique for studies on the wettability of powders.

A vacuum microbalance technique has been used to evaluate the wettability of powders. The rate of uptake, and equilibrium weight of uptake, of water vapour onto outgassed powder samples, of differing wettabilities, were determined at different known temperatures. Standard techniques of data analysis were used to establish the enthalpy, entropy and Gibb's free energy of the activation and adsorption processes. The values obtained appeared to be in the correct order of magnitude and those for activation clearly reflected the relative wettability of the powders. Tests for compensation demonstrated that with the exception of phenobarbitone, there was probably a common mechanism producing the adsorption.

Adsorption↗
PubMed1986

Liquid penetration as a method of assessing the wettability and surface energy of pharmaceutical powders.

The use of a liquid penetration technique to assess the wettability and surface energy of a series of barbiturates, including the use of bicomponent systems, has been critically evaluated. Values of apparent contact angles (theta) obtained using the Washburn relationship (1921) and the Carli & Simioni correction (1979) were found to reflect the practically derived wettability of the powders. Values of gamma c obtained from modified Zisman plots and from Neumann's equation of state did not realistically describe the surface energies of the powders. The nature of alcohol-water mixtures has been examined to assist elucidation of the theoretical problems associated with the technique and to offer a possible explanation for the inadequacies of the surface energy results.

Barbiturates↗