Biomedical subjects

J N Sherwood

Publications and source records attributed to J N Sherwood.

10 recordsLinked to original sources

PubMed2006

Hyper-Rayleigh scattering as a means of monitoring crystal nucleation in solution.

Hyper-Rayleigh scattering is revealed as a very sensitive monitor of cluster formation in solution, and as a means of studying the mechanism of crystal nucleation in molecular species. Two compounds are selected with particularly high second harmonic generation (SHG) powers in the crystalline state and experimental conditions are defined allowing the measurement of the beta value for one of these as 18+/-1x10(-30) esu. It is found to agree with current theoretical prediction of 20x10(-30) esu. In the more powerful of these, two photon induced fluorescence is found to be partly responsible for the SHG. The solubilities of both compounds in methanol are measured and it is observed that these differ by a factor of ten. When the solution concentration is increased beyond 45% of the saturation value, the quadratic coefficient exhibits non-linear behaviour with respect to concentration. Additionally, the widths of the distributions of the HRS signals increase initially with concentration as expected, but, beyond 45% saturation concentrations, these narrow again. These phenomena are interpreted as indicators of cluster formation in these solutions well below saturation concentrations. A future experimental design is proposed in which the coherent component will yield information on the organisation of the molecules in such clusters.

Journal Article↗

PubMed2002

Dissolution kinetics of single crystals of alpha-lactose monohydrate.

The dissolution kinetics of alpha-lactose monohydrate (alphaLM) single crystals were studied by a flow-cell method at different undersaturations. Linear dissolution profiles were obtained as a function of time for all the faces except the (010) face. The dissolution rates, obtained from these profiles, were anisotropic and varied considerably with undersaturation. At low undersaturations (0-2%), the order of dissolution rate was (110) > (100) > (011) = (110) > (010). This order changed with increasing undersaturation (>5%) to (011) >> (100) > (110) > (110) > (010). In alphaLM crystals in which lattice strain was induced by synchrotron X-irradiation, the rates of dissolution of all faces increased with increasing strain. The increase was less significant for the (011) faces than for the remainder. Under this constraint, the (010) face became the fastest dissolving one and the [011]face became the slowest one. The results of all experiments are explained on the basis that although dislocations may act as initiating dissolution centers at very low undersaturations, these sources rapidly give way to two-dimensional nucleation of randomly distributed dissolution sites as the undersaturation is increased. Under these conditions, which better reflect the normal dissolution processes of materials, bulk lattice strain plays the most significant role in defining the dissolution rate. The results show a potential route to the controlled engineering of the dissolution behavior of crystalline materials.

Crystallization↗

PubMed2001

Crystallization of paracetamol from solution in the presence and absence of impurity.

The bulk crystallization of paracetamol has been examined under controlled conditions in the presence and absence of the additive p-acetoxyacetanilide (PAA), as a function of both supersaturation and additive levels. The induction time to nucleation was found to increase with increase in PAA concentration in solution. The product micro-crystals were characterized for shape and strain/defect content using electron and optical microscopy and X-ray Laue diffraction techniques, respectively. A change in crystal habit of the pure crystals from columnar (dominant [110]) to plate-like (dominant [001]) was observed to occur with an increase in supersaturation level, whilst the addition of PAA invariably led to the development of columnar crystals with an aspect ratio that varied with impurity level and supersaturation. HPLC showed the PAA to be incorporated into the crystals with an average segregation coefficient of 14-18% depending on the supersaturation. The ready incorporation of PAA is attributed to the molecular similarity of this molecule to that of the host material. The incorporation is shown to cause a significant increase in the mosaic spread, implying the development of a significant strain/defect content in the crystals. The influence of the impurity on the time to nucleation is probably due to its effect in blocking the development of the critical nucleus. The potential implications of such variations in morphology and strain content in the design of the physical and chemical properties of the resulting particulates are discussed.

Acetaminophen↗

PubMed2001

Polymorphism in 2,4,6-trinitrotoluene crystallized from solution.

An examination has been made of the role of solvent type in the definition of the polymorphic nature of 2,4,6-trinitrotoluene precipitated from solution. A combination of calorimetric and structural techniques including in situ crystallization studies using synchrotron radiation has shown that the variations in polymorphic form following precipitation from solution do not arise specifically from any stereospecific guidance that the nature of the solvent might impose on the structural form. Rather the differences are linked to the variations in solubility and hence supersaturation which might build up prior to nucleation and growth and to the isolation of the metastable orthorhombic phase from the solvent. The final conclusion is that the changes fit well with Ostwald's Law of Stages with the orthorhombic form always precipitating initially followed by its conversion to the stable monoclinic form. The previously observed tendency for some solvents to yield one or the other form then becomes attributable to kinetics in solution rather than structural control. It can be associated with the solubility of the material in the solvent used and the role of this factor in a solvent-mediated phase transformation. On this basis rules can be formulated for the isolation of the metastable forms of this and similarly related polymorphic systems.

Crystallization↗

PubMed2001

The bulk crystallization of alpha-lactose monohydrate from aqueous solution.

The bulk crystallization of alpha-lactose monohydrate from aqueous solution by primary nucleation has been studied under controlled conditions of supersaturation, temperature, and pH. The induction times to nucleation were extremely long compared with those generally observed for other materials, even at the high supersaturations used in the experiment. As a result, it was necessary to stir the supersaturated solution vigorously to induce nucleation in a reasonable but still lengthy working time. Even then, nucleation only occurred to a limited extent, following which growth ceased for 8-10 h before resuming. After this period, growth recommenced but again slowed to a low rate after another 8 h. At this stage, the yield of product was low and in most cases the particles had achieved sizes close to the maximum noted. The yields increased with further crystallization time (22-72 h total from the recommencement of growth) to give, under high initial supersaturation conditions, amounts of product close to the theoretical value. For the most part, however, the particle size did not increase with this later increase in yield, showing only significant changes after the extremely long total crystallization times. It is proposed that these extreme properties result from the formation in solution by mutarotation of the anomer alpha-lactose, which inhibits nucleation as well as its previously observed influence on growth.

Crystallization↗

PubMed2001

Fracture property studies of paracetamol single crystals using microindentation techniques.

PURPOSE: To study the fracture behavior of the major habit faces of paracetamol single crystals using microindentation techniques and to correlate this with crystal structure and molecular packing. METHODS: Vicker's microindentation techniques were used to measure the hardness and crack lengths. The development of all the major radial cracks was analyzed using the Laugier relationship and fracture toughness values evaluated. RESULTS: Paracetamol single crystals showed severe cracking and fracture around all Vicker's indentations with a limited zone of plastic deformation close to the indent. This is consistent with the material being a highly brittle solid that deforms principally by elastic deformation to fracture rather than by plastic flow. Fracture was associated predominantly with the (010) cleavage plane, but was also observed parallel to other lattice planes including (110), (210) and (100). The cleavage plane (010) had the lowest fracture toughness value, Kc = 0.041MPa m1/2, while the greatest value, Kc = 0.105MPa m1/2 was obtained for the (210) plane. CONCLUSIONS: Paracetamol crystals showed severe cracking and fracture because of the highly brittle nature of the material. The fracture behavior could be explained on the basis of the molecular packing arrangement and the calculated attachment energies across the fracture planes.

Acetaminophen↗

PubMed2001

Microhardness and dislocation identification studies on paracetamol single crystals.

PURPOSE: To study the mechanical behaviour of paracetamol single crystals. METHODS: Microhardness indentation techniques were used to study the hardness anisotropy of paracetamol. Solvent etching technique was used to define the range of plastic deformation and the orientation of the dislocation lines. The orientation dependence of Knoop hardness on the (001), (110) and (201) surfaces was compared with calculated values of the Effective Resolved Shear Stress (ERSS) for plastic deformation by specific dislocation types. RESULTS: The principal habit faces of single crystals using both Vickers and Knoop indenters showed a range of hardness from 235 to 456 MPa depending on the type of indenter used and its orientation on the surface. Solvent etching of the plastically deformed region of the crystal around the Vickers/Knoop indentations confirmed that the slip plane was (010). ERSS analysis suggested that the deformation occurred by the slip of dislocations of the types (010)[001] and (010)[100]. Crystals doped with 0.08-0.8 w/w% p-acetoxyacetanilide showed hardness values similar to the pure material. CONCLUSIONS: The low number of distinct dislocation slip systems (two) is characteristic of a brittle material and is consistent with the observation that paracetamol will tolerate only deformations of 1 part in 10(6) before fracture.

Acetaminophen↗

PubMed1979

Health hazard appraisal counseling--continuing evaluation.

A program of annual health examinations was expanded to include counseling based on a computerized appraisal of individual patients' specific health risk factors. Data obtained from a specially designed questionnaire, laboratory tests and a physical examination yielded a health hazard appraisal showing a number of weighted risk factors and their relation to ten leading causes of death as determined for that patient. From all of this information, a "risk age" was developed which could then be compared with the patient's "true age." The results were reviewed with each patient, and methods of correcting health hazards were stressed. The first annual retesting of a group of 107 examinees showed a net risk age reduction of 1.4 years (formerly reported in this journal). The longer term follow-up reported in this paper showed a net risk reduction of 2.38 years in a group of 26 examinees. The net risk age reduction in the two groups represented 32 and 40 percent, respectively, of the achievable risk age reduction when patients comply with suggestions made during risk reduction counseling. These findings indicate that health hazard appraisal counseling is an effective method of altering priorities of health practices.

Adult↗

PubMed1975

Health hazard appraisal in patient counseling.

A program of annual health examinations was expanded to include counseling based on a computerized appraisal of individual patients' specific health hazard factors. Data obtained from a specially designed questionnaire, laboratory tests and a physical examination yielded a printout showing a number of weighted risk factors and their relation to ten leading causes of death as determined for that patient. From all of this information, a risk ("apparent") age was developed for the patient. The results were reviewed with each patient, and methods of correcting health hazards were stressed. A total of 488 persons were appraised, and 107 were randomly reappraised in less than a year, with the finding that the net risk age was reduced by 1.4 years. Such a reduction in risk age is significant; it indicates that appraisal-based counseling is an effective method of altering priorities of health practices.

Accidents↗

PubMed1975

Multiphasic health testing. Benefit-cost analysis of high-volume and low-volume testing programs.

Cost analysis of a low-volume multiphasic health testing program (30 patients/week) has demonstrated that unit costs are similar to those reported by high-volume automated programs (500 patients/week). This comparability in unit costs appears to result from the savings in personnel and space requirements of the smaller program as compared with the larger ones. Cost effectiveness studies (costs per positive findings) of comparable test groups have yielded similar results. This fact leads the authors to suggest that physicians should consider establishing multiphasic health testing programs in occupational and small group medical settings.

Cost-Benefit Analysis↗