M. J. Wilkins

An In Situ Dissolution Study of Aspirin Crystal Planes (100) and (001) by Atomic Force Microscopy

AbstractPurpose. To observe in situ and on individual aspirin crystal faces the comparative rates and processes of dissolution of the dominant faces. Methods. The kinetics of the dissolution rate of two aspirin crystal planes (001) and (100) under 0.05M HCl are studied in situ at room temperature using Atomic Force Microscopy. The dissolution process of each crystal plane was followed by observed changes in topographic features. Results. The results revealed that crystal plane (001) dissolves by receding step edges, and has a dissolution rate of 0.45 nm s−1. Conversely, plane (100) displays crystal terrace sinking at an average rate of 2.93 nm s−1. Calculated intrinsic dissolution values (g s−1 cm−2) for planes (001) and (100) are 1.37 × 10−7 g s−1 cm−2 and 8.36 × 10−7 g s−1 cm−2, respectively. Conclusions. These values indicate that the rate of flux of material from plane (100) is approximately six times greater than that from plane (001), under 0.05M HCl. Interpretation of the data, based upon intrinsic dissolution rates and dissolution rate velocities, correlate with reported variations in the dissolution behavior of commercial aspirin products. These observations illustrate the suitability of the technique for characterizing the dissolution behavior of crystalline drugs.

The Discrimination of Drug Polymorphic Forms from Single Crystals Using Atomic Force Microscopy

established crystallization conditions (4). The only polymorphic Ardeshir Danesh,1 Xinyong Chen,1 forms used pharmaceutically are polymorphs A and B. PolyMartyn C. Davies,1 Clive J. Roberts,1,4 morph A is easier to handle, particularly in large scale operations Giles H. W. Sanders,1,3 Saul J. B. Tendler,1 due to good flow properties, and lack of adherence making Phillip M. Williams,1 and M. J. Wilkins2 it most suitable for manufacturing tablets (4). Polymorph B

Discrimination of polymorphic forms of a drug product by localized thermal analysis

In chemical processing, it is important to distinguish between and identify polymorphic forms. We demonstrate the novel use of scanning thermal microscopy (SThM) and localized thermal analysis to distinguish and identify polymorphic forms of the drug cimetidine. These forms cannot be resolved by classical bulk thermal analysis. SThM reveals a sample consisting of a 50 : 50 mixture of the polymorphs contains regions of different thermal conductivity, corresponding to the different polymorphs. Localized thermal analysis of small volumes of pure polymorphic samples (approximately 50 µm3) shows that the origin of the thermal conductivity contrast lies, at least in part, with the presence of a surface water layer on the more hydrophilic polymorph.

Evaluation of the short-term impact of counseling in general practice

This paper describes the findings of a randomised controlled trial of the short-term impact of counseling in the general practice setting. Compared with patients who received usual advice from their general practitioner for acute problems such as relationship difficulties, anxiety and depression, those who received counseling from qualified counselors working within the primary health care context showed greater improvement in psychological health as measured by the General Health Questionnaire. Significantly fewer of those counselled were prescribed anti-depressant drugs by the general practitioners in the study, or were referred to psychiatrists or clinical psychologists for care. In addition those patients who attended sessions with the practice counselor were more likely to report that they were satisfied with their treatment and more expressed feelings of well-being.

Comparison of scanning tunnelling microscopy and transmission electron microscopy image data of a microbial polysaccharide

Abstract The study of biological material by scanning tunnelling microscopy has led to a need for critical validation of the resultant data. We present here a comparison of scanning tunnelling microscopy images and electron micrographs of a microbial polysaccharide. Xanthan gum in a glycerol solution was sprayed onto mica discs and coated with a platinum/carbon conducting layer and a carbon backing layer. The ability of the scanning tunnelling microscope to image replicas as prepared for electron microscopy is demonstrated. The images of isolated xanthan molecules have comparable contrast to electron micrographs and in addition, contain directly available 3D data. The implications of these results, for future progress in sample preparation for STM studies, are discussed. Further images of xanthan, coated only with platinum/carbon, are used to illustrate that the resolution can be improved by a reduction in the grain size of the coating.

Surface damage of sputtered gold films at the high and low gap resistance settings of a scanning tunnelling microscope

Abstract The use of a scanning tunnelling microscope to alter surface morphology is now established for a number of materials from the atomic scale to the nanometer. Presented here is a novel technique utilizing the field emission mode of the microscope at high bias voltages (i.e., high gap resistances) for the creation of stable features on gold films after the removal of surface material. Further investigations reveal that damage to the gold films may also occur during normal scanning at low, but not unusual, gap resistances. This value was dependent upon the grain size of the film and varied between approximately 100 and 10 M ohm for grain diameters between 3 and 12 nm. This second and separate surface damage phenomena is ascribed to a sweeping effect of the tip as demonstrated by the controlled removal of a gold island at a specific gap resistance.

Observation of a super‐periodic feature on gold with a scanning tunneling microscope

In this letter we present the first reported images of a super‐periodic hexagonal lattice observed on gold in air by scanning tunneling microscopy. The surface features presented extend over large areas (up to 1.0×105 nm2) with an average periodicity of 8 nm, and a corrugation of 1 nm. The impact of comparable results on highly oriented pyrolytic graphite suggests the need for some caution when using gold in biomolecular scanning tunneling microscopy studies.

Scanning Tunneling Microscopy Studies on Xanthan Gum

The application of the scanning tunneling microscope (STM) to imaging biological molecules has generated much interest over recent years. Research has mainly concentrated on obtaining images of DNA, proteins and small organic molecules. However, the work we present concerns polysaccharides, specifically xanthan gum, commonly used in the food and oil industries. We have employed high-resolution metallic shadowing to overcome some of the problems associated with imaging biological molecules by STM, such as tip-sample interaction effects and lack of conduction. The images displayed demonstrate the ability of the STM to image replicas of discrete polysaccharide molecules. We directly correlate and compare these results with electron micrographs of similarly prepared molecules. In addition, the effect of different sample deposition techniques and substrates on the resultant images of xanthan gum is demonstrated. We discuss the implications for sample preparation procedures for future STM studies on biological molecules.

Studies on Xanthan Structure by Scanning Tunnelling Microscopy

Scanning tunnelling microscopy (STM) is a technique for the direct 3D imaging of surface atoms, molecules and biomolecular shapes. The use of the equipment for the imaging of polysaccharides is still in its infancy and techniques have to be established that allow critical evaluation of the images produced by STM. Images of the microbial polysaccharide xanthan using preparation techniques applicable to both the STM and electron microscopy (EM) have been produced, thus enabling comparison of the two techniques.