A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

YesHigh-dose API powders which are to be tableted by direct compression should have high compactibility and compressibility. This note reports on a novel approach to the manufacture of crystalline powders intended for direct compaction with improved compactibility and compressibility properties. The poorly compactable API, chlorothiazide, was spray dried from a water/acetone solvent mix producing additive-free nanocrystalline microparticles (NCMPs) of median particle size 3.5 μm. Tablets compacted from NCMPs had tensile strengths ranging from 0.5 to 4.6 MPa (compared to 0.6–0.9 MPa for tablets of micronised CTZ) at compression forces ranging from 6 kN to 13 kN. NCMP tablets also had high porosities (34–20%) and large specific surface areas (4.4–4.8 m2/g). The time taken for tablets made of NCMPs to erode was not statistically longer (p > 0.05) than for tablets made of micronised CTZ. Fragmentation of NCMPs on compression was observed. The volume fraction of particles below 1 μm present in the suspension recovered after erosion of NCMP tablets was 34.8 ± 3.43%, while no nanosized particles were detected in the slurry after erosion of compacted micronised CTZ.Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/B1158

Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

YesObjectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM:4-ASA cocrystals with different habits in order to investigate the effect on dissolution, and the derived powder properties of flow and compaction. Methods: Cocrystals were prepared in a 1:1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray-drying (habit IV). Key findings: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr’s compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. Conclusions: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behavior.Science Foundation Ireland. Grant Number: SFI/12/RC/227

Self-assembled carrageenan/protamine polyelectrolyte nanoplexes-Investigation of critical parameters governing their formation and characteristics

YesThe aim of this work was to investigate the feasibility of cross-linker free polyelectrolyte complex formation at the nanoscale between carrageenan (CAR) and protamine (PROT). The properties of CAR/PROT nanoparticles (NPs) were dependent on the carrageenan type: kappa (KC), iota (IC) and lambda (LC), concentration of components, addition of divalent cations, weight mixing ratio (WMR) of constituents and mode of component addition. In the case of 0.1% w/v solutions, IC-based NPs had the smallest particle sizes (100-150nm) and low polydispersity indices (0.1-0.4). A decrease in the solution concentration from 0.1% to 0.05% w/v enabled the formation of KC/PROT NPs. All carrageenans exhibited the ability to form NPs with surface charge ranging from -190 to 40mV. The inclusion of divalent cations caused an increase in the particle size and zeta potential. Infrared analysis confirmed the presence of a complex between CAR and PROT and showed that IC chains undergo structural changes when forming NPs. Colloidal stability of NPs was related to the initial surface charge of particles and was time- and pH-dependent. IC was found to be the most suitable type of CAR when forming nanoplexes with PROT

Self-assembled carrageenan/protamine polyelectrolyte nanoplexes-Investigation of critical parameters governing their formation and characteristics

YesThe aim of this work was to investigate the feasibility of cross-linker free polyelectrolyte complex formation at the nanoscale between carrageenan (CAR) and protamine (PROT). The properties of CAR/PROT nanoparticles (NPs) were dependent on the carrageenan type: kappa (KC), iota (IC) and lambda (LC), concentration of components, addition of divalent cations, weight mixing ratio (WMR) of constituents and mode of component addition. In the case of 0.1% w/v solutions, IC-based NPs had the smallest particle sizes (100-150nm) and low polydispersity indices (0.1-0.4). A decrease in the solution concentration from 0.1% to 0.05% w/v enabled the formation of KC/PROT NPs. All carrageenans exhibited the ability to form NPs with surface charge ranging from -190 to 40mV. The inclusion of divalent cations caused an increase in the particle size and zeta potential. Infrared analysis confirmed the presence of a complex between CAR and PROT and showed that IC chains undergo structural changes when forming NPs. Colloidal stability of NPs was related to the initial surface charge of particles and was time- and pH-dependent. IC was found to be the most suitable type of CAR when forming nanoplexes with PROT

Optimisation of the self-assembly process: production of stable, alginate-based polyelectrolyte nanocomplexes with protamine

YesThe aim of this work was to investigate the possibility of covalent cross-linker-free, polyelectrolyte complex formation at the nanoscale between alginic acid (as sodium alginate, ALG) and protamine (PROT). Optimisation of the self-assembly conditions was performed by varying the type of polymer used, pH of component solutions, mass mixing ratio of the components and the speed and order of component addition on the properties of complexes. Homogenous particles with nanometric sizes resulted when an aqueous dispersion of ALG was rapidly mixed with a solution of PROT. The polyelectrolyte complex between ALG and PROT was confirmed by infrared spectroscopy. To facilitate incorporation of drugs soluble at low pH, pH of ALG dispersion was decreased to 2; however, no nanoparticles (NPs) were formed upon complexation with PROT. Adjusting pH of PROT solution to 3 resulted in the formation of cationic or anionic NPs with a size range 70–300 nm. Colloidal stability of selected alginic acid low/PROT formulations was determined upon storage at room temperature and in liquid media at various pH. Physical stability of NPs correlated with the initial surface charge of particles and was time- and pH-dependent. Generally, better stability was observed for anionic NPs stored as native dispersions and in liquids covering a range of pH.This study was funded by Merrion Pharmaceuticals Ireland. This work was also supported by the Synthesis and Solid State Pharmaceutical Centre funded by the Science Foundation Ireland under grant number 12/RC/2275

An Anisotropic Ballistic Deposition Model with Links to the Ulam Problem and the Tracy-Widom Distribution

We compute exactly the asymptotic distribution of scaled height in a (1+1)--dimensional anisotropic ballistic deposition model by mapping it to the Ulam problem of finding the longest nondecreasing subsequence in a random sequence of integers. Using the known results for the Ulam problem, we show that the scaled height in our model has the Tracy-Widom distribution appearing in the theory of random matrices near the edges of the spectrum. Our result supports the hypothesis that various growth models in $(1+1)$ dimensions that belong to the Kardar-Parisi-Zhang universality class perhaps all share the same universal Tracy-Widom distribution for the suitably scaled height variables.Comment: 5 pages Revtex, 3 .eps figures included, new references adde

Women, men and coronary heart disease: a review of the qualitative literature

Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

Older people as equal partners in creative design

Active older people want to be actively engaged by contributing their experiences to design better services and products. This paper demonstrates the importance of older peoples engagement in the creative design process in a small study where older people were engaged together with designers in the design of digital devices. Three creative workshops were conducted: the first with designers, the second with designers and older people, and the third with older people only. During the illumination stage of the creative process flexibility and flow were measured with topics and turns. Results show that when older people were working with designers more topics and a higher total number of turns were developed than by older people or designers working on their own, which indicates that they had the highest flexibility of ideas and possibly also the greatest flow

From dynamical scaling to local scale-invariance: a tutorial

Dynamical scaling arises naturally in various many-body systems far from equilibrium. After a short historical overview, the elements of possible extensions of dynamical scaling to a local scale-invariance will be introduced. Schr\"odinger-invariance, the most simple example of local scale-invariance, will be introduced as a dynamical symmetry in the Edwards-Wilkinson universality class of interface growth. The Lie algebra construction, its representations and the Bargman superselection rules will be combined with non-equilibrium Janssen-de Dominicis field-theory to produce explicit predictions for responses and correlators, which can be compared to the results of explicit model studies. At the next level, the study of non-stationary states requires to go over, from Schr\"odinger-invariance, to ageing-invariance. The ageing algebra admits new representations, which acts as dynamical symmetries on more general equations, and imply that each non-equilibrium scaling operator is characterised by two distinct, independent scaling dimensions. Tests of ageing-invariance are described, in the Glauber-Ising and spherical models of a phase-ordering ferromagnet and the Arcetri model of interface growth.Comment: 1+ 23 pages, 2 figures, final for

Dynamic Ordering and Transverse Depinning of a Driven Elastic String in a Disordered Media

We examine the dynamics of an elastic string interacting with quenched disorder driven perpendicular and parallel to the string. We show that the string is the most disordered at the depinning transition but with increasing drive partial ordering is regained. For low drives the noise power is high and we observe a 1/f^2 noise signature crossing over to a white noise character with low power at higher drives. For the parallel driven moving string there is a finite transverse critical depinning force with the depinning transition occuring by the formation of running kinks.Comment: 4 pages, 4 postscript figure