Medical Applications of Solid State Ionics

Solid State Ionic materials and devices are being used in medicine in many ways. A brief initial introduction to the materials, the devices and the pertinent electrophysiological and clinical aspects is presented. To exemplify the breadth of SSI material and device applications, an overview is given of three main areas: Biomedical applications of solid state power sources; Biofuel cells; and Iontophoretic and related devices used for controlled transdermal drug delivery and monitoring of physiological parameter

Itraconazole Amorphous Solid Dispersion Tablets: Formulation and Compaction Process Optimization Using Quality by Design Principles and Tools

open access articleBCS Class II drugs, such as itraconazole (ITZ), exhibit poor solubility (1–4 ng/mL) and so require solubility enhancement. Therefore, ITZ and Kollidon® VA64 (KOL) amorphous solid dispersions (ASDs) were produced using hot-melt extrusion (HME) to improve ITZ’s poor solubility. A novel strategy for tablet formulations using five inorganic salts was investigated (KCl, NaCl, KBr, KHCO3 and KH2PO4 ). These kosmotopric salts are thought to compete for water hydration near the polymer chain, hence, preventing polymer gelation and, therefore, facilitating disintegration and dissolution. Out of all the formulations, the KCl containing one demonstrated acceptable tensile strength (above 1.7 MPa), whilst providing a quick disintegration time (less than 15 min) and so was selected for further formulation development through a design of the experiment approach. Seven ITZ-KOL-ASD formulations with KCl were compacted using round and oblong punches. Round tablets were found to disintegrate under 20 min, whereas oblong tablets disintegrated within 10 min. The round tablets achieved over 80% ITZ release within 15 min, with six out of seven formulations achieving 100% ITZ release by 30 min. It was found that tablets comprising high levels of Avicel® pH 102 (30%) and low levels of KCl (5%) tend to fail the disintegration target due to the strong bonding capacity of Avicel® pH 102. The disintegration time and tensile strength responses were modeled to obtain design spaces (DSs) relevant to both round and oblong tablets. Within the DS, several formulations can be chosen, which meet the Quality Target Product Profile (QTPP) requirements for immediate-release round and oblong tablets and allow for flexibility to compact in different tablet shape to accommodate patients’ needs. It was concluded that the use of inorganic salts, such as KCl, is the key to producing tablets of ITZ ASDs with fast disintegration and enhanced dissolution. Overall, ITZ-KOL-ASD tablet formulations, which meet the QTPP, were achieved in this study with the aid of Quality by Design (QbD) principles for formulation and compaction process development and optimization

Conducting polymers and polymer electrolytes.

Polymers are mostly used as insulator materials. Since the late sixties, two new classes of polymeric materials possessing either ionic or electronic conductivities have been extensively studied. The work carried out in this thesis concerns of the study of polymer electrolytes based on poly(ethylene oxide) (PEO) complexed with divalent salts (ionic conductors) and polypyrroles (PPy) electrochemically and chemically prepared (electronic conductors). Different techniques were used to study their properties including Differential Scanning Calorimetry (DSC), Variable Temperature Polarising Microscopy (VTPM), Extended X-ray Absorption Fine Structure (EXAFS), a.c. Impedance, Cyclic Voltammetry, and Fourier Transform Infra-Red Spectroscopy (FTIR). Water-cast films of PEOn:ZnX2 (X = C1, Br, I) were prepared at a range of stoichiometries. The effects of either residual presence of water or thermal treatment related to the formation of high melting crystalline materials were investigated. The morphology of the zinc halides films differs from similar films cast from acetonitrile/methanol mixtures. The presence of high melting crystalline material in the water cast samples is influenced mostly by the concentration, type of anion and drying procedure applied to the samples. The high melting crystalline materials in the zinc samples are more affected by the drying regime. In some cases, solvent effects can be removed by using a high temperature (e.g. 180°C) drying regime. The presence of water normally depresses the melting temperature of the crystalline structures. Films of PEOn.:CaBr2 and PEOn:NiBr2 cast from water were also examined. The high melting crystalline materials in the calcium samples are more affected by the presence of water. The nickel samples are highly crystalline and the presence of high melting material does not seem to be influenced by either the presence of solvent or the drying procedure. EXAFS was used as a suitable technique to probe the local structure surrounding the cation. The results of the zinc halide samples gave some indication of the interionic and polymer-cation interactions. It was demonstrated that the halogen provides the most substantial contribution for the total EXAFS spectrum and the oxygen contribution is much less significant, except in the case of PEOn:ZnC12 samples. This could be due to the size of the nearest neighbour atoms and/or to the interaction polymer-cation. The presence of neutral "ion pairing" is suggested for the PEOn:ZnBr2 samples. The EXAFS results for the samples containing NiBr2 indicated a strong interaction between polymer-salt and the local structure was dependent on concentration, unlike the zinc samples. The polymerisation of pyrrole was investigated by using chemical and electrochemical oxidation routes. The structural characterisation of the compounds obtained was limited by their insolubility. The electrochemically prepared samples presented higher conductivity than the ones which were chemically prepared. The EXAFS results at the Fe K-edge of the PPyFeCl4 sample, which was prepared by direct chemical oxidation, suggested that the iron is coordinated to oxygens at a distance 1.97 A, chlorines at 3.08 A and perhaps nitrogens at 3.72 A. The iron local structure of the composite PVA/PPy doped with FeCl3 was different from the PPyFeCl4 sample. The iron in the composite sample was coordinated to oxygens at 1.98 A and chlorines at 2.18 A. Alternatively, the presence of a distorted FeCl4- is considered

In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon® VA64 amorphous solid dispersions. The influence of die temperature, screw speed, solid feed rate and PRX concentration on the critical quality attributes (CQAs) absorbance and lightness of color (L*) of the extrudates was investigated using multivariate tools. Statistical analysis results show interaction effects between concentration and temperature on absorbance and L* values. Solid feed rate has a significant effect on absorbance only and screw speed showed least impact on both responses for the screening design. The optimum HME process conditions were confirmed by 4 independent studies to be 20% w/w of PRX, temperature 140 °C, screw speed 200 rpm and feed rate 6 g/min. The in-line UV-Vis system was used to assess the solubility of PRX in Kollidon® VA64 by measuring absorbance and L* values from 230 to 700 nm. Oversaturation was observed for PRX concentrations higher than 20% w/w. Oversaturation can be readily identified as it causes scattering in the visible range. This is observed by a shift of the baseline in the visible part of the spectrum. Extrudate samples were analyzed for degradation using off-line High-Performance Liquid Chromatography (HPLC) standard methods. Results from off-line experiments using differential scanning calorimetry (DSC), and X-ray diffraction (XRD) are also presented

Manganese Mono-Substituted Borotungstate: Characterization and Catalytic Application

The Keggin-type TBA(4)H(2)[BW11Mn(H2O)O-39]center dot H2O (BW11Mn) compound was isolated and characterized. The first sphere of coordination for the manganese atom was determined by EXAFS analysis. Six oxygen atoms were found in the range of 1.80-2.64 angstrom from the manganese. BW11Mn showed to be an active, efficient and selective catalyst for cis-cyclooctene (la) epoxidation in the presence of stoichiometric quantities of H2O2. After 5 h of reaction almost complete conversion was achieved (86% of conversion). Selectivity was always 100 % for the epoxide