Solubility parameter based screening methods for early stage formulation development of itraconazole amorphous solid dispersions

Objectives: This article uses conventional and newly extended solubility parameter (δ) methods to identify polymeric materials capable of forming amorphous dispersions with itraconazole (itz). Methods: Combinations of itz and Soluplus, Eudragit E PO (EPO), Kollidon 17PF (17PF) or Kollidon VA64 (VA64) were prepared as amorphous solid dispersions using quench cooling and hot melt extrusion. Storage stability was evaluated under a range of conditions using differential scanning calorimetry and powder X-ray diffraction. Key findings: The rank order of itz miscibility with polymers using both conventional and novel δ-based approaches was 17PF > VA64 > Soluplus > EPO, and the application of the Flory–Huggins lattice model to itz–excipient binary systems corroborated the findings. The solid-state characterisation analyses of the formulations manufactured by melt extrusion correlated well with pre-formulation screening. Long-term storage studies showed that the physical stability of 17PF/vitamin E TPGS–itz was poor compared with Soluplus and VA64 formulations, and for EPO/itz systems variation in stability may be observed depending on the preparation method. Conclusion: Results have demonstrated that although δ-based screening may be useful in predicting the initial state of amorphous solid dispersions, assessment of the physical behaviour of the formulations at relevant temperatures may be more appropriate for the successful development of commercially acceptable amorphous drug products.

Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds.

Catchment and in-stream influences on metal concentration and ochre deposit density in upland streams, Northern Ireland

Metal concentrations from stream waters in two geological blocks in Northern Ireland were compared to determine the contributions of catchment characteristics and in-stream conditions. One block is composed of metamorphosed schist and unconsolidated glacial drift with peat or peaty podzol (mainly humic) soils, while the other block consists of tertiary basalt with brown earth and gley soils. Water samples were collected from 52 stream sites and analysed for Fe, Mn and Al as well as a range of other chemical determinands known to affect metal solubility. Densities of metal-rich ochre deposit were determined for stream bed stone samples. Higher conductivities and concentrations of bicarbonate, alkalinity, Ca and Mg occurred on basalt than on schist. Despite higher Fe and Mn oxide concentrations in basalt-derived non-humic soils, stream water concentrations were much lower and ochre deposit densities only one third of those on schist overlain by humic soils. Neither rock nor soil type predicted Al concentrations, but pH and dissolved oxygen did. Peat-generated acidity and the limited acid neutralising capacity of base-poor metamorphosed schist have resulted in elevated concentrations of metals and ochre deposit in surface waters.

Laboratory measurements of resistivity in warm dense plasmas relevant to the microphysics of brown dwarfs

Since the observation of the first brown dwarf in 1995, numerous studies have led to a better understanding of the structures of these objects. Here we present a method for studying material resistivity in warm dense plasmas in the laboratory, which we relate to the microphysics of brown dwarfs through viscosity and electron collisions. Here we use X-ray polarimetry to determine the resistivity of a sulphur-doped plastic target heated to Brown Dwarf conditions by an ultra-intense laser. The resistivity is determined by matching the plasma physics model to the atomic physics calculations of the measured large, positive, polarization. The inferred resistivity is larger than predicted using standard resistivity models, suggesting that these commonly used models will not adequately describe the resistivity of warm dense plasma related to the viscosity of brown dwarfs.

Impacto fisiológico do parasita dinoflagelado Amyloodinium ocellatum (Brown, 1931) em corvina-legítima (Argyrosomus regius, Asso, 1801) produzida em aquacultura

Dissertação de mestrado, Biologia Marinha, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Old St. David's, Cheraw, South Carolina, 1770-1947

A history of Old St. David's Church in Cheraw, SC from 1770 to 1947.