Peter Hornsby

Physicochemical characterization and drug-release properties of celecoxib hot-melt extruded glass solutions.

The interest in hot‐melt extrusion (HME) as a drug delivery technology for the production of glass solutions is growing rapidly. HME glass solutions have a tendency to recrystallize during storage and also typically have a very dense structure, restricting the ingress of dissolution fluid and retarding drug release. In this study, we have used HME to manufacture glass solutions containing celecoxib (CX) and polyvinylpyrrolidone (PVP) and have assessed the use of supercritical carbon dioxide (scCO2) as a pore‐forming agent to enhance drug release. Differential scanning calorimetry confirmed the formation of glass solutions following extrusion. All extrudates exhibited a single glass transition temperature (Tg), positioned between the Tg values of CX and PVP. The instability of glass solutions is a significant problem during storage. Stabilization may be improved through the appropriate choice of excipient to facilitate drug–polymer interactions. The Gordon–Taylor equation showed that the Tg values of all extrudates expected on ideal mixing were lower than those observed experimentally. This may be indicative of drug–polymer interactions that decrease free volume and elevate the Tg. Molecular interactions between CX and PVP were further confirmed using Fourier transform infrared and Raman spectroscopy. Storage stability of the extrudates was shown to be dependent on drug loading. Samples containing a higher CX loading were less stable, which we ascribed to decreased Tg and hence increased mobility within the drug–polymer matrix. The solubility of CX was improved through the formulation of extruded glass solutions, but release rate was relatively slow. Exposure of extrudates to scCO2 had no effect on the solid‐state properties of CX but did produce a highly porous structure. The drug‐release rate from extrudates after scCO2 exposure was significantly higher.

Novel Supercritical Carbon Dioxide Impregnation Technique for the Production of Amorphous Solid Drug Dispersions: A Comparison to Hot Melt Extrusion

The formulation of BCS Class II drugs as amorphous solid dispersions has been shown to provide advantages with respect to improving the aqueous solubility of these compounds. While hot melt extrusion (HME) and spray drying (SD) are among the most common methods for the production of amorphous solid dispersions (ASDs), the high temperatures often required for HME can restrict the processing of thermally labile drugs, while the use of toxic organic solvents during SD can impact on end-product toxicity. In this study, we investigated the potential of supercritical fluid impregnation (SFI) using carbon dioxide as an alternative process for ASD production of a model poorly water-soluble drug, indomethacin (INM). In doing so, we produced ASDs without the use of organic solvents and at temperatures considerably lower than those required for HME. Previous studies have concentrated on the characterization of ASDs produced using HME or SFI but have not considered both processes together. Dispersions were manufactured using two different polymers, Soluplus and polyvinylpyrrolidone K15 using both SFI and HME and characterized for drug morphology, homogeneity, presence of drug-polymer interactions, glass transition temperature, amorphous stability of the drug within the formulation, and nonsink drug release to measure the ability of each formulation to create a supersaturated drug solution. Fully amorphous dispersions were successfully produced at 50% w/w drug loading using HME and 30% w/w drug loading using SFI. For both polymers, formulations containing 50% w/w INM, manufactured via SFI, contained the drug in the γ-crystalline form. Interestingly, there were lower levels of crystallinity in PVP dispersions relative to SOL. FTIR was used to probe for the presence of drug-polymer interactions within both polymer systems. For PVP systems, the nature of these interactions depended upon processing method; however, for Soluplus formulations this was not the case. The area under the dissolution curve (AUC) was used as a measure of the time during which a supersaturated concentration could be maintained, and for all systems, SFI formulations performed better than similar HME formulations.

Biorefining of perennial ryegrass for the production of nanofibrillated cellulose

This study has demonstrated biorefining steps for ryegrass and silage at a pilot scale to extrude fibre cake for the production of nanofibrillated cellulose (NFC), a potentially green biomaterial for replacing conventional fillers in the manufacture of polymer composites. Further treatments of processed ryegrass fibres with mechanical shearing, microfluidising, hydrochloric acid (HCl)/sulphuric acid and a four stage {ethylenediaminetetra-acetic acid, sodium hydroxide, sodium hypochlorite and HCl} hydrolysis yielded 43.8, 36.1, 25.6 and 39.8 kg t−1 DM of NFCs respectively. The NFCs were characterised using microscopy, X-ray diffraction, dynamic light scattering, spectroscopy and thermogravimetry. The NFC had diameters from 3.0–9.1 nm and length 308 nm–4.6 μm. NFC-polyvinyl alcohol composites containing NFC (5 wt%) exhibited enhanced Youngs modulus and thermal stability by factors of 2.5 and 2 respectively compared with control. The mass, energy, water and chemical balances of the four process steps were assessed to evaluate technical feasibility and also to provide baseline production data for scaling up. The microfluidised product has been identified as the best NFC product, but production cost needs to be reduced.

Preparation and characterisation of nanocellulose reinforced polyamide-6

Abstract A procedure is described for preparing polyamide-6 (PA-6) reinforced with cellulose nanofibres. The cellulose nanofibres were obtained from flax and microcrystalline cellulose (MCC) using combinations of acid hydrolysis, ball milling and ultrasound, then characterised by transmission electron microscopy (TEM) in order to determine their size and geometry. The nanofibres produced from the different feedstock sources were of a similar order with lengths ranging from 21 to 300 nm and diameters between 2 and 22 nm. PA-6 nanocomposite films were subsequently prepared from these nanofibres using a solution casting technique. Their chemical and physical structure was analysed using Fourier transform infrared analysis (FTIR) and TEM. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were also applied to compare their thermal properties with unfilled polymer. Dynamic mechanical thermal analysis and tensile measurements demonstrated a significant enhancement in mechanical properties was possible with a low addition of cellulose nanofibres to the polymer matrix.

Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.

Banana and Abaca Fiber-Reinforced Plastic Composites Obtained by Rotational Molding Process

Natural fibers can be used in rotational molding process to obtain parts with improved mechanical properties. Different approaches have been followed in order to produce formulations containing banana or abaca fiber at 5% weight, in two- and three-layer constructions. Chemically treated abaca fiber has also been studied, causing some problems in processability. Fibers used have been characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), optical microscopy, and single-fiber mechanical tests. Rotomolded parts have been tested for tensile, flexural, and impact properties, demonstrating that important increases in elastic modulus are achieved with these fibers, although impact properties are reduced.

Thermoforming carbon fibre-reinforced thermoplastic composites

The use of carbon fibre composites is growing in many sectors but their use remains stronger in very high value industries such as aerospace where the demands of the application more easily justify the high energy input needed and the corresponding costs incurred. This energy and cost input is returned through gains over the whole life of the product, with for example, longer maintenance intervals for an aircraft and lower fuel burn. Thermoplastic composites however have a different energy and cost profile compared to traditional thermosets with notable differences in recyclability, but this profile is not well quantified or documented. This study considers the key process control parameters and identifies an optimal window for processing, along with the effect this has on the final characteristics of the manufactured parts. Interactions between parameters and corresponding sensitivities are extracted from the results.

Mould fouling of elastomers during injection moulding

Abstract A systematic study of mould fouling during elastomer injection moulding is presented. Moulding was undertaken principally using nitrile rubber compound and purpose built tooling with interchangeable mould inserts. Rubber metal interactions between treated and untreated Stavax steel surfaces were characterised by a variety of analytical techniques to study factors influencing the onset of mould fouling and its origins. Preliminary simulation and supporting experimental investigation suggested that the design and location of the gate influenced both mould filling pattern and the position of rubber deposition within the cavity.

Preparation and Properties of Polyphenylene Sulfide/Multi‐walled Carbon Nanotube Composites

Polyphenylene sulphide (PPS)/multi‐walled carbon nanotube (MWCNT) composites were prepared using a melt‐blending procedure combining centrifugal pre‐mixing and twin‐screw extrusion. A homogeneous dispersion of MWCNTs throughout the matrix was revealed by scanning electron microscopy for the nanocomposites with MWCNT contents ranging from 0.5 to 8.0 wt%. The presence of the MWCNTs showed both promotion and retardation effects on the crystallization of PPS. The competition between these two effects results in an unusual change of the degree of crystallinity with increasing MWCNT content. The mechanical properties of PPS were markedly enhanced by the incorporation of MWCNTs.