Search

Abstract: Phosphorylcholine (PC) moieties were chemically attached to surfaces of polymer microparticles by addition of 2-methylacryloyloxyethyl phosphorylcholine monomer to the seeded, semi-continuous polymerisations of methyl methacrylate (MMA) and butyl acrylate (BA). The surface of the bio-functionalised polymer microparticles was principally characterised using X-ray photoelectron spectroscopy (XPS), dynamic nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), acoustophoresis and enzyme-linked immunosorbent assays (ELISA). It was found that the persulphate initiating species are concealed behind the phosphorylcholine containing monomer sequence located on the surface of the microparticles. The combination of analytical techniques showed that the surfaces of the polymer microparticles are extremely mobile above the glass transition temperature of the co-polymer and able to rearrange depending on the environment in which they are placed. This allows the phosphorylcholine moiety to be preferentially expressed at the surface in aqueous media, but not so in the dry state or conditions of ultra-high vacuum. In terms of the nature of the biocompatibility of phosphorylcholine containing polymers, no evidence was found for the irreversible structuring of water molecules around the phosphorylcholine moiety in the wet state. The results of this work suggest that a more likely contributory reason for the protein-resistant nature of phosphorylcholine containing polymers is the mobility of the phosphorylcholine moiety. Increases in biocompatibility correspond with increases in the hydrophilicity of a polymer surface when phosphorylcholine is preferentially expressed. A large free water fraction may be present in the phosphorylcholine containing monomer sequence, as part of a hydrogel structure located at the surface of the polymer microparticles. This, coupled with concomitant modification of the local electrical double-layer very close to the surface may also play a critical role in reducing protein–surface interactions. [Copyright &y& Elsevier]

Abstract: Zwitterionic surfactants based on phosphorylcholine and sulfobetaine have been used as emulsifiers to prepare stable, monodisperse copolymer latices of methyl methacrylate and butyl acrylate at high volume fractions using seeded semi-continuous emulsion copolymerisation. The amounts of these surfactants required when semi-continuously fed into the preparation are more than an order of magnitude less than is conventionally used. The low amounts of emulsifier used in successful polymerisations allowed subtle features of the mechanism of polymerisation for this system to be revealed. At specific surfactant concentrations in the polymerisations, the results suggested that the rate of incorporation of surfactant into the growing primary polymer particle was greater than the rate of addition. This led to primary particle instability and a coagulative mechanism being the dominant nucleation mechanism. This occurred at points at or just above the critical micelle concentration (CMC). The total number of particles formed was proportional to the concentration of surfactant to the 0.87–1.48 power and is consistent with Gilberts analysis on the coagulative nucleation mechanism. This suggests that at other surfactant concentrations above and below the CMC for each zwitterionic surfactant used, the presence of a classical homogenous or micellar nucleation mechanism, each coupled with a coagulative process could be present, although the experimental data presented are not conclusive. The surfactants were found to be crucial to the stability of the growing latex particle, but their mechanism of action is still unclear. The final polymer latex particles were electrostatically stabilised, at least in part, by the persulphate initiator fragments. [Copyright &y& Elsevier]

Abstract: When assessing the suitability of potential drug/polymer systems for improving drug bioavailability, substantial efficiency gains can be achieved through the development and application of rapid miniaturised screening methods. For this to be possible new methods of small-scale formulation manufacture that produce materials equivalent to full-scale manufacture are urgently required. In this work, we use Atomic Force Microscopy (AFM) and Confocal Raman Microscopy (CRM) to investigate the potential physical and chemical equivalence of individually dried particles generated using a DRYING KINETICS ANALYZER™ (DKA) with material from a conventional spray-drier. For our model system of griseofulvin (at loadings of 2.5%, w/w and 20%, w/w) and PEG 6000, the results demonstrate physicochemical equivalence between the two spray-drying methods for the same drug loading. Thus we suggest that single particle spray drying offers a viable and novel route to the production of materials for miniaturised methods of screening candidate drug/polymer formulations. [Copyright &y& Elsevier]

Absolute calibration relates the measured (arbitrary) intensity to the differential scattering cross section of the sample, which contains all of the quantitative information specific to the material. The importance of absolute calibration in small-angle scattering experiments has long been recognized. This work details the absolute calibration procedure of a small-angle X-ray scattering instrument from Bruker AXS. The absolute calibration presented here was achieved by using a number of different types of primary and secondary standards. The samples were: a glassy carbon specimen, which had been independently calibrated from neutron radiation; a range of pure liquids, which can be used as primary standards as their differential scattering cross section is directly related to their isothermal compressibility; and a suspension of monodisperse silica particles for which the differential scattering cross section is obtained from Porod's law. Good agreement was obtained between the different standard samples, provided that care was taken to obtain significant signal averaging and all sources of background scattering were accounted for. The specimen best suited for routine calibration was the glassy carbon sample, due to its relatively intense scattering and stability over time; however, initial calibration from a primary source is necessary. Pure liquids can be used as primary calibration standards, but the measurements take significantly longer and are, therefore, less suited for frequent use. [ABSTRACT FROM AUTHOR]

Abstract: Formation of a solid solution of a drug in a water-soluble polymer is one of the primary techniques used to improve the dissolution rate and thus bioavailability of a poorly water-soluble drug. Understanding and detecting the state of the drug inside such a polymer matrix is critically important since issues such as drug stability, safety and efficacy can be greatly affected. In this study, two model formulations were prepared containing low and high levels of drug content. The heterogeneity of the formulations has been investigated using a novel nanothermal analysis technique. This technique has demonstrated a promising capability for imaging and quantitatively characterising the nanoscale properties of solid dispersion formulations. [Copyright &y& Elsevier]