Additive manufacturing in pharmaceutical formulation - Development of biodegradable printed dosage forms for oral drug delivery

The main focus of pharmaceutical research and development in recent decades has gradually shifted from synthesis of new drug molecules towards personalized (precision) medicine, where the drug dosage and release rate are tailored in order to fit the needs of each specific patient. Together with new discoveries in diagnostics and pharmacogenomics, this has led to increased need for novel formulation methods, which would enable to dynamically adjust the characteristics of each produced dosage form (such as tablet, pill, capsule, etc.). Amongst the most promising techniques is 3D printing of tablets or films, a subject of a rising number of published articles, especially after the FDA approval of the first printed tablet, Spritam. The Fused Deposition Modelling (FDM) technique is most frequently cited, since it’s commercially available and offers the possibility to produce biodegradable dosage forms with defined drug contents and complex inner structures (affecting the drug’s release rate), potentially also containing multiple drugs with varying release profiles Please click Additional Files below to see the full abstract

Effective transport properties of drug delivery systems: Porous granules and tablets

Solid dosage forms such as tablets, granules or capsules represent over 80% of all pharmaceutical products. Modern pharmaceutical formulations are designed so as to release the active pharmaceutical ingredient (API) at a well-defined and reproducible rate. Two main classes of dosage forms can be distinguished: rapid release formulations (which are designed to disintegrate rapidly and dissolve the API within the shortest possible time), and sustained release formulations (which are designed to release the API gradually over a prolonged period of time, typically 24 hours). In both cases, the effective transport properties of the drug carrier (granule, tablet) play a crucial role. Please download the full abstract below

The wall shear rate distribution for flow in random sphere packings

The wall shear rate distribution P(gamma) is investigated for pressure-driven Stokes flow through random arrangements of spheres at packing fractions 0.1 <= phi <= 0.64. For dense packings, P(gamma) is monotonic and approximately exponential. As phi --> 0.1, P(gamma) picks up additional structure which corresponds to the flow around isolated spheres, for which an exact result can be obtained. A simple expression for the mean wall shear rate is presented, based on a force-balance argument.Comment: 4 pages, 3 figures, 1 table, RevTeX 4; significantly revised with significantly extended scop

Light-responsive hydrogel microcrawlers, powered and steered with spatially homogeneous illumination

Sub-millimeter untethered locomoting robots hold promise to radically change multiple areas of human activity such as microfabrication/assembly or health care. To overcome the associated hurdles of such a degree of robot miniaturization, radically new approaches are being adopted, often relying on soft actuating polymeric materials. Here, we present light-driven, crawling microrobots that locomote by a single degree of freedom actuation of their light-responsive tail section. The direction of locomotion is dictated by the robot body design and independent of the spatial modulation of the light stimuli, allowing simultaneous multidirectional motion of multiple robots. Moreover, we present a method for steering such robots by reversibly deforming their front section, using ultraviolet (UV) light as a trigger. The deformation dictates the robot locomotion, performing right- or left-hand turning when the UV is turned on or off respectively. The robots' motion and navigation are not coupled to the position of the light sources, which enables simultaneous locomotion of multiple robots, steering of robots and brings about flexibility with the methods to deliver the light to the place of robot operation

MODELISATION DES PHENOMENES DE TRANSFERT ET DE REACTIONS DANS DES MILIEUX HETEROGENES COMPLEXES

PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Adsorption of Carbon Dioxide on Porous Catalyst Materials at Near-Critical Conditions

Herein, the construction of a manometric adsorption apparatus has been described and an experimental method has been developed to measure the adsorption of carbon dioxide on porous materials at sub-critical pressures. The materials used are silica gel and silica loaded with 5 mol% ZnO; γ-alumina and alumina with 5 mol% ZnO. It was observed that the addition of zinc oxide causes a 50–100% increase of the adsorbed amount at 350 K. However, this manometric apparatus is only suitable for relatively large adsorbed amounts due to its sensitivity and precision limitations

Mathematical modelling and FTIR spectroscopic imaging of pharmaceutical tablet dissolution

The process of pharmaceutical tablet dissolution is a vital stage in the delivery of active pharmaceutical ingredients (APIs). The constituent components and their spatial arrangement within the tablet determine the release characteristics of the API. It is therefore important to understand and characterise the various processes and component interactions that occur during tablet dissolution. Computational simulations of tablet dissolution can be used to obtain parametric sensitivities and optimise formulations so that the desired API release profile is achieved. This thesis describes the methods behind modelling the behaviour of non-swelling and swelling tablets, the mathematical validation of the models, parametric studies and the experiments which were used to obtain parameters and verify the models. The experimental method used in this work is Fourier Transform Infrared (FTIR) spectroscopic imaging, which, when using an attenuated total reflection (ATR) accessory and flow cell, enable chemical and spatial information to be obtained from the tablet as it dissolves. UV/Visible spectroscopy was also used to obtain drug release information. The non-swelling model discretised a tablet over a Cartesian grid and solved the mass transfer equations (dissolution and diffusion) to obtain drug release profiles. Two parametric studies were conducted where the particle size distribution and mass fractions were varied in one, and the API diffusivity, saturated concentration and mass fraction in the other to see what effect these had on drug release, demonstrating the importance of the choice of excipient and the impact of particle size on release variability. For experimental validation, tablets containing different quantities of polyethylene glycol and nicotinamide were dissolved and imaged, and optimisation was used to obtain the pure component saturated concentrations. The model was then tested against a different tablet to demonstrate the predictive capability of the model. The swelling model discretised a tablet into small cylindrical particles, whose size was proportional to the mass of components within them and whose motion was determined using the Discrete Element Method (DEM). As water diffused into polymer particles, they could expand, resulting in macroscopic swelling. The DEM model of a swelling and dissolving tablet was validated against a numerically exact model of the same tablet and parametric studies were conducted into the effect of polymer disentanglement threshold, polymer equilibrium water fraction and polymer dissolution rate. The model was also optimised against a dissolving tablet containing HPMC to obtain parameters for this excipient. To conclude, both models were implemented, validated and found to accurately describe the dissolution kinetics of both swelling and non-swelling tablets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Catalytic reaction engineering of propene epoxidation with hydrogen peroxide over titanium silicalite (TS-1)

Propene oxide is an important chemical intermediate in the chemical industry. The propene oxide industry has employed two different types of commercial processes for several decades: the chlorohydrin process and the hydroperoxidation process. However, direct epoxidation of propene with hydrogen peroxide has recently attracted much attention as a more environmentally benign and profitable process. This thesis presents the catalytic reaction engineering of the epoxidation of propene to propene oxide using hydrogen peroxide as the oxidant and titanium silicalite (TS-1) as the catalyst under mild conditions. The kinetics of the heterogeneous catalytic epoxidation was studied in an autoclave reactor using methanol/water mixtures as the solvent. The effects of stirring speed, catalyst loading, reactant concentration, reaction temperature, solvent composition and solvent variation on the propene oxidation are presented and discussed. The catalytic performance of TS-1 impregnated with precious metal nanoparticles such as gold and palladium for the propene epoxidation was also investigated. The influences of the kind of precious metal and treatment process adopted in the catalyst preparation on the propene epoxidation and the hydrogen peroxide decomposition were explored. One of the key objectives of this research was to evaluate a new continuous reactor concept for propene epoxidation and other liquid-phase selective oxidation reactions. A conventional monolith and a confined Taylor flow (CTF) reactor were studied for the propene epoxidation. The influences of gas and liquid flow rates on the hydrodynamics of the structured reactors were investigated under Taylor flow regime at atmospheric pressure. It was found that the variation of hydrodynamics had a significant impact on the production of propene oxide. The effect of operating pressure on the propene oxide production was studied in a pressurised system. In addition, the performances of various structures of reactor column were examined to compare.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (EPSRC)GBUnited Kingdo