Biomedical subjects

Stephen Edge

Publications and source records attributed to Stephen Edge.

13 recordsLinked to original sources

PubMed2025

qcCHIP: an R package to identify clonal hematopoiesis variants using cohort-specific data characteristics.

SUMMARY: Clonal hematopoiesis (CH) is a molecular biomarker associated with various adverse outcomes in both healthy individuals and those with underlying conditions, including cancer. Detecting CH usually involves genomic sequencing of individual blood samples followed by robust bioinformatics data filtering. We report an R package, qcCHIP, a bioinformatics pipeline that implements permutation-based parameter optimization to guide quality control filtering and cohort-specific CH identification. We benchmark qcCHIP under various data settings, including different sequencing depths, ranges of cohort sizes, with and without normal-tumor paired samples, and across different cancer types. We show that qcCHIP allows users to customize analysis needs to generate CH calls based on cohort-specific data characteristics. AVAILABILITY AND IMPLEMENTATION: qcCHIP R package is freely accessible at GitHub https://github.com/tenglab/qcCHIP and DOI: 10.5281/zenodo.16421861.

Humans↗

PubMed2006

Novel temperature controlled surface dissolution of excipient particles for carrier based dry powder inhaler formulations.

The surface of lactose monohydrate was modified by solution phase variable temperature dissolution. Lactose monohydrate crystals were added to a known volume of a saturated solution of lactose monohydrate at 25 degrees C. The temperature of the mixture was then ramped to either 30, 35, 40, or 50 degrees C to produce lactose monohydrate batches with reduced levels of fines and lower surface roughness. A dramatic decrease in surface roughness with increasing dissolution temperature was visually observed using scanning electron microscopy. Particle size analysis suggested that the level of lactose fines was reduced after treatment at the lowest dissolution temperature, 30 degrees C. Evaluation of the samples' drug aerosolization using a twin stage impinger, after blending with salbutamol sulphate, suggested that even though there were dramatic changes in roughness and particle size distribution after surface dissolution at 30 degrees C, there was no significant difference in aerosolization as measured by fine particle fraction. However, after surface dissolution at 35 degrees C, there was an increase in fine particle fraction. Surface dissolution at even higher temperatures did not result in any further increase in fine particle fraction. These observations suggest that surface roughness and fines play an important role in the aerosolization of salbutamol sulphate, but the inter-relationships are not straightforward.

Adrenergic beta-Agonists↗

PubMed2005

Comparative study of erythritol and lactose monohydrate as carriers for inhalation: atomic force microscopy and in vitro correlation.

The adhesion of micronised salbutamol sulphate to two carrier excipients, lactose monohydrate and erythritol, was investigated using the atomic force microscope (AFM) colloid probe technique and correlated with their respective physico-mechanical properties and aerosolisation performance. The particle size, morphology and moisture sorption properties of the carriers were similar thereby allowing direct comparison of functionality. AFM force measurements (n = 1024 force curves) were obtained between salbutamol sulphate drug probes (n = 4) and the excipients, as 63-90 microm sieve fractions and atomically smooth crystals. In general, significant differences in drug adhesion to lactose monohydrate and erythritol were observed (ANOVA, p<0.05), with erythritol exhibiting relatively greater adhesiveness. A linear relationship between drug probe adhesion to lactose monohydrate and drug probe adhesion to erythritol was established with salbutamol sulphate-lactose monohydrate adhesion being 60-70% of that of the erythritol system. In vitro analysis suggested good correlation with the adhesion measurements. The aerosolisation of salbutamol sulphate from erythritol carrier particles was significantly less (ANOVA, p<0.05) than from lactose monohydrate, with a fine particle dose (<6.4 microm) of 41.9 +/- 7.4 microg and 24.9 +/- 3.1 microg for the lactose monohydrate and erythritol carriers, respectively (n = 3).

Administration, Inhalation↗

PubMed2005

The influence of dose on the performance of dry powder inhalation systems.

The relationship between drug/lactose ratio and aerosolisation performance of conventional carrier based formulations was investigated using the twin stage impinger. A dose range of approximately 10-450 microg of drug in a 50 mg lactose carrier formulation was studied. Statistical differences in both the fine particle dose and fine particle fraction were observed across the dosage range (ANOVA, p<0.05). In general, no statistically significant difference (Fishers Pairwise, p<0.05) in fine particle dose was observed between drug levels of approximately 10 microg and 135 microg, whereas a linear decrease in fine particle fraction was observed across the same drug level range (R2=0.977). Increasing the dose from approximately 135 microg to 450 microg resulted in a statistically significant increase in both fine particle dose and fraction (ANOVA p<0.05). Such observations may be attributed to the occupation of 'active' carrier sites by drug particles at low drug concentration, since the quantity of drug particles liberated from the carrier during aerosolisation remains constant at the lower dosing regimes.

Drug Delivery Systems↗

PubMed2005

Dynamic vapor sorption properties of sodium starch glycolate disintegrants.

Dynamic vapor sorption (DVS) was used to determine the moisture sorption properties of sodium starch glycolates. The results were compared to similarly obtained data for potato starch, pregelatinized starch, microcrystalline cellulose (MCC), and crystalline lactose. As expected, sodium starch glycolates exhibit a large mass gain at 90% relative humidity (RH), compared to the other anhydroglucose-based excipients. However, the sorption capacities of potato starch and the modified starches between 10%-70% RH were similar. Analysis of the DVS data using the Brunauer-Emmett-Teller (BET) and Guggenheim, Anderson, and deBoer (GAB) theories to obtain the so-called monolayer (Xm), as expected, showed that there was an increasing Xm with apparent mass gain that is probably related to crystallinity, purity, and surface area and represents the number and accessibility of amorphous anhydroglucose units present. The value of x(m) was related to the degree of crystallinity or order as determined by X-ray diffraction, suggesting that x(m) can be used to further describe the amorphous nature of semi-crystalline polymers containing anhydroglucose units, in particular the chemically modified sodium starch glycolate. Additionally, it appears that the sorption capacity between 10%-70% RH is not dramatically affected by the presence or type of cross-linking and sodium carboxymethylation (in sodium starch glycolates) and gelatinization (in pregelatinized starch) and that the superdisintegrant properties of the sodium starch glycolates are a consequence of some water-structure interaction that is well beyond the available number of hydration sites, as represented by x(m). Further evaluation of the structure and sorption properties of excipients may aid the development of disintegrants for solid dosage forms.

Absorption↗

PubMed2004

The potential use of Raman mapping to investigate in vitro deposition of combination pressurized metered-dose inhalers.

Scanning near-infrared Raman microscopy has been used to map aerosol particulate deposits produced from pressurized metered-dose inhalers (pMDI). A commercially available combination asthma therapy pMDI (Ventide, Allen and Hanbury, UK), containing salbutamol and beclometasone dipropionate, was analyzed by conventional in vitro quantitative analysis and scanning Raman microscopy. Raman maps, taken from Andersen cascade impactor plate stages 3 and 5 (over 100 x 100 microm areas) suggested good correlation with chemical analysis of the respective stages. Scanning Raman microscopy allows visual differentiation between formulation components (not possible using conventional imaging techniques), while potentially allowing chemical quantification.

Aerosols↗

PubMed2004

Influence of particle size and shape on flowability and compactibility of binary mixtures of paracetamol and microcrystalline cellulose.

The influence of the size and shape of paracetamol particles on the flow and compression behavior of blends (1:1) of microcrystalline cellulose (MCC) was investigated. The effect of paracetamol particle shape was investigated by using two differently prepared samples, micronized and novel engineered Solution Atomization and Xstallization by Sonication (SAXS) particles, which exhibited similar particle size ranges (2-6 microm). The results were compared to data obtained for an untreated paracetamol sample. The blends containing SAXS particles exhibited increased bulk and tapped density and improved flow, compared to the blend containing micronized particles. This may reflect differences in shape since the SAXS particles exhibited spherical morphology. The compressibility of the blend containing untreated paracetamol was greater than blends containing the SAXS and micronized materials, which may reflect the different drug particle sizes and shapes. However, blends containing the needle-shaped particles of pure untreated sample, exhibited poor compactibility after storage at 10% RH. It was found that increasing the moisture content in the blends by storage at 44% RH resulted in an increase in the compactibility of the samples containing untreated and SAXS paracetamol with the blends containing micronized paracetamol being relatively unaffected. In general, tablets prepared from blends containing smaller particles of paracetamol exhibited significantly greater compactibility compared to tablets prepared containing the larger particle sized untreated paracetamol. The use of small, spherical drug particles may result in improvements in the bulk density, densification and compactibility of blends of paracetamol and microcrystalline cellulose.

Acetaminophen↗

PubMed2004

Physicochemical and mechanical evaluation of a novel high density grade of silicified microcrystalline cellulose.

High density microcrystalline cellulose (MCC) is a relatively free flowing grade of MCC that finds use in direct compression tableting and hard gelatin capsule filling applications. Silicified high density microcrystalline cellulose has recently been introduced. This material has been compared to other grades of MCC and previously silicified microcrystalline cellulose (SMCC). The results suggest that, as observed for other grades of SMCC, the material exhibits no detectable chemical or polymorphic differences to standard material, some improvement in flow characteristics, but shows considerably enhanced mechanical properties.

Cellulose↗

PubMed2003

Under pressure: predicting pressurized metered dose inhaler interactions using the atomic force microscope.

Drug particulate interactions in pressurized metered dose inhalers (pMDI) may lead to a decrease in aerosolization efficiency and subsequent efficacy in patient treatment. The interactions between salbutamol sulfate (commonly used in Ventolin pMDIs) and a series of pMDI canister materials were investigated using the atomic force microscope (AFM) colloid probe technique. Approximately 4000 individual force-distance curves were determined for a drug probe and three surfaces (10 x 10 mum areas) in situ, in a model propellant. The area under each force-distance curve was integrated to obtain separation energy values. Median separation energy values followed the rank order borosilicate glass > aluminum > PTFE, suggesting PTFE to be the most suitable canister coating.

Administration, Inhalation↗

PubMed2003

The effect of mechanical processing on surface stability of pharmaceutical powders: visualization by atomic force microscopy.

Atomic force microscopy was used to investigate the influence of mechanical processing (milling) on the surface stability of salbutamol sulfate. Phase imaging, a development of tapping mode atomic force microscopy, was used to elucidate variations in the physico-mechanical properties on the surface of salbutamol sulfate crystals by measuring the phase lag of an oscillating tip in contact with the surface. Simultaneous measurements of topographical and phase images indicated an increase in disorder on the surface as milling time was increased. Specific regions on the milled samples, independent of topography, showed large variations in phase shift (> 30 degrees). These regions (not observed on the crystalline salbutamol sulfate) suggested large differences in the physical properties on the surface. It is therefore reasonable to conclude that these regions were likely attributed to mechanically induced amorphous domains.

Drug Stability↗

PubMed2003

Adsorption of an amine drug onto microcrystalline cellulose and silicified microcrystalline cellulose samples.

The adsorption of a model amine drug (tacrine hydrochloride) from aqueous solution onto 21 microcrystalline cellulose (MCC) based samples has been investigated. The MCC source (manufacturer) affected adsorption. The adsorption appeared to be fully reversible. Adsorption was reduced by the use of high-density grade MCC, high-energy milling, and silicification. Adsorption of the model drug was not affected by the particle size of the MCC. Significant variations of the adsorption characteristics between batches of certain MCC products were found. The primary mode of adsorption was by ion exchange.

Adsorption↗

PubMed2002

Outcome with postmastectomy radiation with transverse rectus abdominis musculocutaneous flap breast reconstruction.

The effects of radiation on the outcome of patients undergoing transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction have not been extensively studied. Concern still exists of a possible negative impact secondary to irradiation as related to control of disease, cosmetic outcome, and flap viability. Thirty-six patients underwent both a modified radical mastectomy (MRM) with TRAM flap reconstruction and irradiation to the chest wall to include the TRAM flap and/or regional nodes either before reconstruction or after TRAM flap reconstruction. Fifteen patients had all of their treatment and follow-up at our institution and were retrospectively reviewed to assess treatment and outcome. During a median follow-up of 36 months there were no local-regional failures. One patient at Stage IIIA failed with distant metastases 3 years after treatment. One patient had a flap loss from a nonhealing wound after reconstruction performed 2 years after MRM and radiotherapy. Only one patient expressed dissatisfaction with the cosmetic outcome. Patients undergoing MRM with TRAM flap reconstruction and irradiation before or after reconstruction can achieve excellent local-regional control and satisfactory cosmesis. Risk of flap loss is low. Further follow-up is needed for assessing longer-term outomes in this patient group. Larger prospective studies are necessary for more definitive conclusions.

Adult↗

PubMedDate not supplied

Continued investigation into the influence of loaded dose on the performance of dry powder inhalers: surface smoothing effects.

The aerosolization of salbutamol sulfate, measured as fine particle dose (FPD LD) and fine particle fraction (FPF LD) (<6.4 microm mass median aerodynamic diameter), from two sieved (63-90 microm) lactose monohydrate carriers, one as supplied, one smoothed by controlled surface dissolution, was studied. In general, no significant variation in FPD LD was observed at drug loadings between 10 and 63.5 microg and 10 and 135 microg for the surface dissolved and as supplied lactose monohydrates, respectively. Increasing the drug load above these levels resulted in linear increases in FPD LD with increasing drug load with the surface dissolved lactose monohydrate exhibiting higher FPD LD and FPF LD. This suggests that, at lower drug loadings, areas of the carrier exhibiting higher adhesion, so-called active sites, were being preferentially occupied and filled. Since there was no evidence of drug agglomeration using scanning electron microscopy, the observations suggest that the number and range of such higher energy "active sites" can be reduced by modifying the surface roughness, that is, energies, of the carrier.

Administration, Inhalation↗