Biomedical subjects

Philip H Rowe

Publications and source records attributed to Philip H Rowe.

5 recordsLinked to original sources

PubMed2004

Effect of lubricant type and concentration on the punch tip adherence of model ibuprofen formulations.

A model formulation, comprising ibuprofen and direct compression lactose (Tablettose 80) was used to assess the influence of two lubricants, magnesium stearate and stearic acid, on punch tip adherence. Lubricant concentrations were varied from 0.25% to 2% w/w. Formulations in the presence and absence of 0.5% w/w colloidal silica (Aerosil 200) were examined, to assess the influence of the glidant on the anti-adherent effects of the lubricants. Differential scanning calorimetry (DSC) was used to examine the effect of the lubricants on the melting temperature of ibuprofen. Tablets were compacted using a single punch tablet press at 10 kN using hard chrome-plated punches or at 40 kN using uncoated steel punches, tooling was 12.5-mm diameter in each case. The upper punch faces were characterized by obtaining Taylor Hobson Talysurf surface profiles. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. At low concentrations of each lubricant, the levels of sticking observed were similar. Whilst sticking increased at magnesium stearate concentrations above 1%, sticking with stearic acid remained relatively constant at all concentrations. DSC revealed that the melting temperature of ibuprofen was lowered by the formation of eutectic mixtures with both lubricants. However, the onset temperature of melting and melting point were lowered to a greater extent with magnesium stearate compared with stearic acid. When using uncoated tooling at 40 kN, the deleterious effects of magnesium stearate on the tensile strength of the tablets also contributed to sticking. When using chrome-plated punches at 10 kN, the tensile strength reduction by the presence of magnesium stearate was less pronounced, as was the level of sticking.

Adhesiveness↗

PubMed2004

Effect of punch tip geometry and embossment on the punch tip adherence of a model ibuprofen formulation.

The sticking of a model ibuprofen-lactose formulation with respect to compaction force, punch tip geometry and punch tip embossment was assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Three sets of 'normal' concave punches were used to evaluate the influence of punch curvature and diameter. The punches were 10, 11 and 12 mm in diameter, respectively. The 10-mm punch was embossed with a letter 'A' logo to assess the influence of an embossment on sticking. Flat-faced punches (12.5 mm) were used for comparison with the concave tooling. Surface profiles (Taylor Hobson Talysurf 120) of the upper punch faces were obtained to evaluate the surface quality of the tooling used. Following compaction, ibuprofen attached to the upper punch face was quantified by spectroscopy. Increasing punch curvature from flat-faced punches to concave decreased sticking. Altering punch diameter of the concave punches had no effect on sticking when expressed as microg mm(-2). The embossed letter 'A' logo increased sticking considerably owing to the probable concentration of shear stresses at the lateral faces of the embossed logo.

Adhesiveness↗

PubMed2003

Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations.

The sticking of three model ibuprofen-lactose formulations with respect to compaction force and the surface quality of the upper punch were assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Two sets of 12.5-mm flat-faced punches were used to evaluate the influence of surface quality. A third set of chrome-plated tooling was also used. Surface profiles (Taylor Hobson Talysurf 120) of the normal tooling upper punches indicated a large difference in quality. The punches were subsequently classified as old (Ra = 0.33 microm) or new (Ra = 0.04 microm) where Ra is the mean of all positive deviations from zero. Surface profiles of sample tablets were also obtained. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. Punch surface roughness, compaction force and the blend composition were all significant factors contributing to sticking. Chrome plating of punch faces increased sticking at a low compaction force but decreased sticking at higher forces. Surface roughness of the tablets did not correlate with the corresponding data for sticking, indicating that this is not a suitable method of quantifying sticking.

Adhesiveness↗

PubMed2002

Comparative assessment of methods to develop QSARs for the prediction of the toxicity of phenols to Tetrahymena pyriformis.

Quantitative structure-activity relationships (QSARs) for the toxicity of 200 phenols to the ciliated protozoan Tetrahymena pyriformis, and the validation of the QSARs using a test set of a further 50 compounds, are reported. The phenols are structurally heterogeneous and represent a variety of mechanisms of toxic action including polar narcosis, weak acid respiratory uncoupling, electrophilicity, and those compounds capable of being metabolised or oxidised to quinones. For each compound, a total of 108 physico-chemical descriptors have been calculated. A variety of methods were utilised to develop QSARs and are compared. The response-surface, or two parameter, approach was found to be successful, but only following the removal of compounds known to form quinones. Stepwise regression produced a seven parameter QSAR with good statistical fit, but was less interpretable and transparent than the response-surface. Partial least squares produced a good model for phenolic toxicity following supervised selection of parameters, this, however, was the least transparent of all approaches attempted. In all approaches, a large number of outliers were observed, typically these were compounds capable of being metabolised to quinones. The strengths and weaknesses of each of the approaches to predict the toxicity of the validation (test) set of phenols to T. pyriformis are discussed.

Animals↗

PubMedDate not supplied

Structure-based classification of antibacterial activity.

The aim of this study was to develop a simple quantitative structure-activity relationship (QSAR) for the classification and prediction of antibacterial activity, so as to enable in silico screening. To this end a database of 661 compounds, classified according to whether they had antibacterial activity, and for which a total of 167 physicochemical and structural descriptors were calculated, was analyzed. To identify descriptors that allowed separation of the two classes (i.e. those compounds with and without antibacterial activity), analysis of variance was utilized and models were developed using linear discriminant and binary logistic regression analyses. Model predictivity was assessed and validated by the random removal of 30% of the compounds to form a test set, for which predictions were made from the model. The results of the analyses indicated that six descriptors, accounting for hydrophobicity and inter- and intramolecular hydrogen bonding, provided excellent separation of the data. Logistic regression analysis was shown to model the data slightly more accurately than discriminant analysis.

Anti-Bacterial Agents↗