Karl Walton

Variable-focus microscopy and UV surface dissolution imaging as complementary techniques in intrinsic dissolution rate determination

This work reports a novel approach to the assessment of the surface properties of compacts used in Surface Dissolution Imaging (SDI). SDI is useful for determining intrinsic dissolution rate (IDR), an important parameter in early stage drug development. Surface topography, post-compaction and post-SDI run, have been measured using a non-contact, optical, three-dimensional microscope based on focus variation, the Alicona Infinite Focus Microscope, with the aim of correlating the IDRs to the surface properties. Ibuprofen (IBU) was used as a model poorly-soluble drug. DSC and XRD were used to monitor possible polymorphic changes that may have occurred post-compaction and post-SDI run. IBUs IDR decreased from 0.033mg/min/cm2 to 0.022mg/min/cm2 from 10 to 20min, respectively, during the experiment. XRD and DSC showed no form changes during the SDI run. The surface topography images showed that a distinct imprint was embossed on the surfaces of some compacts which could affect IDRs. Surface parameter values were associated with the SDI experiments which showed strong correlations with the IDR values. The variable-focus microscope can be used as a complimentary tool in the determination of IDR values from the SDI.

High fidelity replication of surface texture and geometric form of a high aspect ratio aerodynamic test component

This paper details, assesses and validates a technique for the replication of a titanium wind tunnel test aerofoil in polyurethane resin. Existing resin replication techniques are adapted to overcome the technical difficulties associated with casting a high aspect ratio component. The technique is shown to have high replication fidelity over all important length-scales. The blade chord was accurate to 0.02%, and the maximum blade thickness was accurate to 2.5%. Important spatial and amplitude areal surface texture parameter were accurate to within 2%. Compared to an existing similar system using correlation areal parameters the current technique is shown to have lower fidelity and this difference is discussed. The current technique was developed for the measurement of boundary layer flow‘laminar to turbulent’ transition for gas turbine compressor blade profiles and this application is illustrated.

The Limitations of Using “Ra” to Describe Surface Roughness

Current criteria used to determine whether rough surfaces affect skin friction typically rely on a single amplitude parameter to characterize the roughness. The most commonly used criteria relate the centerline averaged roughness, Ra, to an equivalent sandgrain roughness size, ks. This paper shows that such criteria are oversimplified and that Ra/ks is dependent on the roughness topography, namely, the roughness slope defined as the roughness amplitude normalized by the distance between roughness peaks, Ra/λ. To demonstrate the relationship, wake traverses were undertaken downstream of an aerofoil with various polished surfaces. The admissible roughness Reynolds number (ρ1u1Ra/μ1) at which the drag rose above the smooth blade case was determined. The results were used to demonstrate a 400% variation in Ra/ks over the roughness topographies tested. The relationship found held for all cases tested, except those where the roughness first initiated premature transition at the leading edge. In these cases, where the roughness was more typical of eroded aerofoils, the drag was found to rise earlier.

The Limitations of “Ra” to Describe Surface Roughness

Current criteria used to determine whether rough surfaces affect skin friction typically rely on a single amplitude parameter to characterize the roughness. The most commonly used criteria relate the centreline averaged roughness, Ra, to an equivalent sandgrain roughness size, ks. This paper shows that such criteria are oversimplified and that Ra/ks is dependent on the roughness topography, namely the roughness slope defined as the roughness amplitude normalized by the distance between roughness peaks, Ra/λ. To demonstrate the relationship, wake traverses were undertaken downstream of an aerofoil with various polished surfaces. The admissible roughness Reynolds number (ρ1u1Ra/μ1) at which the drag rose above the smooth blade case, was determined. The results were used to demonstrate a 400% variation in Ra/ks over the roughness topographies tested. The relationship found held for all cases tested, except those where the roughness first initiated premature transition at the leading edge. In these cases, where the roughness was more typical of eroded aerofoils, the drag was found to rise earlier.

Direct imaging of the dissolution of salt forms of a carboxylic acid drug

Graphical abstract Figure. No Caption available. HighlightsDecrease in IDR with an increase in chain length of the counterion observed using UV‐imaging.Developed interfacial area ratio (Sdr) showed significant surface gains for the compacts for IDR determination.Particulates on surface compacts and observed cracks responsible for inflated IDR values.Imaging of surface should be taken into consideration prior IDR determination. ABSTRACT The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts. Gemfibrozil (GEM) was used as a model poorly soluble drug. Four salts of GEM were made using cyclopropylamine (CPROP), cyclobutylamine (CBUT), cyclopentylamine (CPENT) and cyclohexylamine (CHEX) as counterions. DSC, XRD and SEM were used to confirm and characterise salt formation. IDR obtained using UV‐imaging up to 10 min for all the salts showed that an increase in the chain length of the counterion caused a decrease in the IDR. Past the 10 min mark, there was an increase in the IDR value for the CPROP salt, which was visualised using UV‐imaging. The developed interfacial (surface) area ratio (Sdr) showed significant surface gains for the compacts. Full dosage form (capsule) imaging showed an improvement over the GEM for all the salts with an increase in chain length of the counterion bringing about a decrease in dissolution which correlated with the obtained UV‐imaging IDR data.