Effect of mechanical denaturation on surface free energy of protein powders

yesGlobular proteins are important both as therapeutic agents and excipients. However, their fragile native conformations can be denatured during pharmaceutical processing, which leads to modification of the surface energy of their powders and hence their performance. Lyophilized powders of hen egg-white lysozyme and β-galactosidase from Aspergillus oryzae were used as models to study the effects of mechanical denaturation on the surface energies of basic and acidic protein powders, respectively. Their mechanical denaturation upon milling was confirmed by the absence of their thermal unfolding transition phases and by the changes in their secondary and tertiary structures. Inverse gas chromatography detected differences between both unprocessed protein powders and the changes induced by their mechanical denaturation. The surfaces of the acidic and basic protein powders were relatively basic, however the surface acidity of β-galactosidase was higher than that of lysozyme. Also, the surface of β-galactosidase powder had a higher dispersive energy compared to lysozyme. The mechanical denaturation decreased the dispersive energy and the basicity of the surfaces of both protein powders. The amino acid composition and molecular conformation of the proteins explained the surface energy data measured by inverse gas chromatography. The biological activity of mechanically denatured protein powders can either be reversible (lysozyme) or irreversible (β-galactosidase) upon hydration. Our surface data can be exploited to understand and predict the performance of protein powders within pharmaceutical dosage forms

The influence of hydroalcoholic media on the performance of Grewia polysaccharide in sustained release tablets

Co-administration of drugs with alcohol can affect the plasma concentration of drugs in patients. It is also known that the excipients used in the formulation of drugs may not always be resistant to alcohol. This study evaluates effect of varying alcohol concentrations on theophylline release from two grades of Grewia mollis polysaccharides. X-ray microtomography showed that native polysaccharide formulation compacts were not homogenous after the mixing process resulting in its failure in swelling studies. Removal of starch from the native polysaccharide resulted in homogenous formulation compacts resistant to damage in high alcoholic media in pH 6.8 (40%v/v absolute ethanol). Destarched polymer compacts had a significantly higher hardness (375 N) than that of the native polysaccharide (82 N) and HPMC K4 M (146 N). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57-91) in simulated gastric media (pH 1.2). The dissolution profiles in the simulated intestinal fluids were also similar (f2 = 60-94), with the exception of the native polysaccharide in pH 6.8 (40%v/v absolute ethanol) (f2 = 43). This work highlights the properties of Grewia polysaccharide as a matrix former that can resist high alcoholic effects therefore; it may be suitable as an alternative to some of the commercially available matrix formers with wider applications for drug delivery as a cheaper alternative in the developing world

Thermodynamics of clay – Drug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography

An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance. Several characterisation techniques as well as isothermal calorimetry were utilized in investigating the adsorption process of a model cationic drug (diltiazem hydrochloride, DIL) onto a pharmaceutical clay system (magnesium aluminium silicate, MAS). X-ray powder diffraction (XRPD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and optical microscopy confirmed the successful formation of the DIL-MAS complexes. Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride (DC-DIL) in the 2 M HCl media. Here also, the authors report for the first time two binding processes that occurred for DIL and MAS. A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable. This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes

Impact of purification on physicochemical, surface and functional properties of okra biopolymer

© 2017 Elsevier Ltd The functionality of plant-resourced biopolymers depends on their physicochemical properties. In addition, the extraction protocol and further processing conditions can significantly affect the effectiveness of biopolymer in diverse industrial applications. Therefore, the objective of this study was to investigate the impact of purification on chemical composition, molecular arrangement, solubility, swelling, erosion, wettability, quantitative wetting kinetics, surface energy and three-dimensional (3D) surface texture properties of okra biopolymer and its compacted form. FTIR and XRD results confirmed that the purification process had no effect on the molecular structural arrangement. The highest purity grade (bi-purified okra biopolymer) had the highest sugar content, solubility, matrix tablet swelling, wettability and surface energy, although the surface porosity and roughness of matrix tablet were low. Okra biopolymer showed pH-dependent solubility and the maximum solubility was achieved at pH 7.4. The mechanism of swelling of less-purified matrices was anomalous, where the rate of water diffusion and polymer relaxation was of the same magnitude, whereas bi-purified matrices showed diffusion-controlled swelling. Wetting was absorption-controlled and the bi-purified biopolymer had a high degree of wetting and surface energy. The extraction method, therefore, has a major influence on the properties and the subsequent drug delivery, biotechnology and food science applications for the biopolymer

Real time calorimetric characterisation of clay – drug complex dispersions and particles

Isothermal titration calorimetry (ITC) along with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and high-performance liquid chromatography (HPLC) were employed to investigate the process of adsorption of propranolol hydrochloride (PPN) onto magnesium aluminium silicate (MAS) and to characterise the MAS-PPN particles formed upon complexation. The composition of MAS was confirmed by infrared (IR) spectroscopy and a calcimeter. The calorimetric results confirmed the binding between PPN and MAS at various pHs and temperatures. The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy. These findings suggest that the binding process was enthalpically driven and entropically unfavourable (lower affinity) suggesting hydrogen bonding and electrostatic interactions dominating the interaction. The variation of pH and temperature did not have a great impact on the thermodynamics of the binding process, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG). A slight reduction in the binding affinity (Ka) with varing pH and temperature was however observed. SEM/EDX studies showed the occurrence of changes in the microstructural properties of MAS following complexation which may explain the potential of MAS-PPN complexes for controlled drug release promoting pharmaceutical innovation

The position of graptolites within Lower Palaeozoic planktic ecosystems.

An integrated approach has been used to assess the palaeoecology of graptolites both as a discrete group and also as a part of the biota present within Ordovician and Silurian planktic realms. Study of the functional morphology of graptolites and comparisons with recent ecological analogues demonstrates that graptolites most probably filled a variety of niches as primary consumers, with modes of life related to the colony morphotype. Graptolite coloniality was extremely ordered, lacking any close morphological analogues in Recent faunas. To obtain maximum functional efficiency, graptolites would have needed varying degrees of coordinated automobility. A change in lifestyle related to ontogenetic changes was prevalent within many graptolite groups. Differing lifestyle was reflected by differing reproductive strategies, with synrhabdosomes most likely being a method for rapid asexual reproduction. Direct evidence in the form of graptolithophage 'coprolitic' bodies, as well as indirect evidence in the form of probable defensive adaptations, indicate that graptolites comprised a food item for a variety of predators. Graptolites were also hosts to a variety of parasitic organisms and provided an important nutrient source for scavenging organisms

Child oral health and preventive dental service access among children with intellectual disabilities, autism and other educational additional support needs: a population-based record linkage cohort study

Objective: Inequalities in child oral health are a global challenge and the intersection of socioeconomic factors with educational additional support needs (ASN), including children with intellectual disabilities or autism, have thus far received limited attention in relatively small clinical studies. We aimed to address this evidence gap by investigating oral health and access to preventive dental services among children with ASN compared to the general child population. Methods: Cohort study linking data from six Scotland-wide health and education databases compared: dental caries experience and tooth extraction via general anaesthetic; receipt of school-based dental inspection; access to primary care and hospital dental services; and access to the Childsmile national oral health improvement programme between children with a range of ASN (intellectual disabilities, autism, social and other) and their peers for the school years 2016/17–2018/19 (n = 166 781). Results: Children with any ASN had higher rates of caries experience than those with no ASN, however, after adjustment for socioeconomic deprivation, sex, year, and school type only those with a social or other ASN remained at increased risk. Rates of tooth extraction under general anaesthesia in hospital were higher among children with intellectual disabilities (aRR = 1.67;95% CI = [1.16–2.37]). School-based dental inspection access improved for children with intellectual disability and/or autism from 2016/17 onwards, although higher rates of child refusal on the day were observed in these groups (no ASN refusal: 5.4%; intellectual disability: 35.8%; autism: 40.3%). Children with any ASN were less likely to attend primary dental-care regularly, and in those who attended, children with intellectual disability or autism were less likely than their peers to receive prevention (fluoride varnish, oral-hygiene instruction, or dietary advice). Childsmile nursery-supervised toothbrushing programme access among children with any ASN was similar to children with no ASN and children with intellectual disability (aRR = 1.27;95% CI = [1.12–1.45]) or autism (aRR = 1.32;95% CI = [1.19–1.45]) were more likely to receive support from Childsmile dental health support worker. Conclusions: We have identified inequalities in oral health and dental care for children with different ASN in Scotland with both a greater burden of disease among some groups and higher complexity of care; compounded by reduced and variable access to preventive dental services. Further efforts are needed to develop and improve preventive care pathways for children with ASN and integrate oral health to wider healthcare systems for these children to mitigate against oral health inequalities

Evaluation of a national complex oral health improvement programme: a population data linkage cohort study in Scotland

Objectives Child dental caries is a global public health challenge with high prevalence and wide inequalities. A complex public health programme (Childsmile) was established. We aimed to evaluate the reach of the programme and its impact on child oral health. Setting Education, health and community settings, Scotland-wide. Interventions Childsmile (national oral health improvement programme) interventions: nursery-based fluoride varnish applications (FVAs) and supervised daily toothbrushing, community-based Dental Health Support Worker (DHSW) contacts and primary care dental practice visits—delivered to the population via a proportionate universal approach. Participants: 50 379 children (mean age=5.5 years, SD=0.3) attending local authority schools (2014/2015). Design: Population-based individual child-level data on four Childsmile interventions linked to dental inspection survey data to form a longitudinal cohort. Logistic regression assessed intervention reach and the independent impact of each intervention on caries experience, adjusting for age, sex and area-based Scottish Index of Multiple Deprivation (SIMD). Outcome measures: Reach of the programme is defined as the percentage of children receiving each intervention at least once by SIMD fifth. Obvious dental caries experience (presence/absence) is defined as the presence of decay (into dentine), missing (extracted) due to decay or filled deciduous teeth. Results: 15 032 (29.8%) children had caries experience. The universal interventions had high population reach: nursery toothbrushing (89.1%), dental practice visits (70.5%). The targeted interventions strongly favoured children from the most deprived areas: DHSW contacts (SIMD 1: 29.5% vs SIMD 5: 7.7%), nursery FVAs (SIMD 1: 75.2% vs SIMD 5: 23.2%). Odds of caries experience were markedly lower among children participating in nursery toothbrushing (>3 years, adjusted OR (aOR)=0.60; 95% CI 0.55 to 0.66) and attending dental practice (≥6 visits, aOR=0.55; 95% CI 0.50 to 0.61). The findings were less clear for DHSW contacts. Nursery FVAs were not independently associated with caries experience. Conclusions: The universal interventions, nursery toothbrushing and regular dental practice visits were independently and most strongly associated with reduced odds of caries experience in the cohort, with nursery toothbrushing having the greatest impact among children in areas of high deprivation

Under What Conditions Can Recursion Be Learned? Effects of Starting Small in Artificial Grammar Learning of Center-Embedded Structure

It has been suggested that external and/or internal limitations paradoxically may lead to superior learning, that is, the concepts of starting small and less is more (Elman,; Newport,). In this paper, we explore the type of incremental ordering during training that might help learning, and what mechanism explains this facilitation. We report four artificial grammar learning experiments with human participants. In Experiments 1a and 1b we found a beneficial effect of starting small using two types of simple recursive grammars: right-branching and center-embedding, with recursive embedded clauses in fixed positions and fixed length. This effect was replicated in Experiment 2 (N = 100). In Experiment 3 and 4, we used a more complex center-embedded grammar with recursive loops in variable positions, producing strings of variable length. When participants were presented an incremental ordering of training stimuli, as in natural language, they were better able to generalize their knowledge of simple units to more complex units when the training input “grew” according to structural complexity, compared to when it “grew” according to string length. Overall, the results suggest that starting small confers an advantage for learning complex center-embedded structures when the input is organized according to structural complexity

(Re)constructing Dimensions

Compactifying a higher-dimensional theory defined in R^{1,3+n} on an n-dimensional manifold {\cal M} results in a spectrum of four-dimensional (bosonic) fields with masses m^2_i = \lambda_i, where - \lambda_i are the eigenvalues of the Laplacian on the compact manifold. The question we address in this paper is the inverse: given the masses of the Kaluza-Klein fields in four dimensions, what can we say about the size and shape (i.e. the topology and the metric) of the compact manifold? We present some examples of isospectral manifolds (i.e., different manifolds which give rise to the same Kaluza-Klein mass spectrum). Some of these examples are Ricci-flat, complex and K\"{a}hler and so they are isospectral backgrounds for string theory. Utilizing results from finite spectral geometry, we also discuss the accuracy of reconstructing the properties of the compact manifold (e.g., its dimension, volume, and curvature etc) from measuring the masses of only a finite number of Kaluza-Klein modes.Comment: 23 pages, 3 figures, 2 references adde