Michael D. Mantle

Quantitative ultra‐fast MRI of HPMC swelling and dissolution

For the first time quantitative Rapid Acquisition with Relaxation Enhancement (RARE) based ultra-fast two-dimensional magnetic resonance imaging has been used to follow the dissolution of hydroxypropylmethyl cellulose (HPMC) in water. Quantitative maps of absolute water concentration, spin-spin relaxation times and water self-diffusion coefficient are obtained at a spatial resolution of 469 microm in less than 3 min each. These maps allow the dynamic development of the medium release rate HPMC/water system to be followed. It is demonstrated that the evolution of the gel layer and, in particular, the gradient in water concentration across it, is significantly different when comparing the quantitative RARE sequence with a standard (nonquantitative) implementation of RARE. The total gel thickness in the axial direction grows faster than that in the radial direction and that the dry core initially expands anisotropically. Additionally, while HPMC absorbs a large amount of water during the dissolution process, the concentration gradient of water within the gel layer is relatively small. For the first time MRI evidence is presented for a transition swollen glassy layer which resides between the outer edge of the dry tablet core and the inner edge of the gel layer.

Mesoscopic structuring and dynamics of alcohol/water solutions probed by terahertz time-domain spectroscopy and pulsed field gradient nuclear magnetic resonance.

Terahertz and PFG-NMR techniques are used to explore transitions in the structuring of binary alcohol/water mixtures. Three critical alcohol mole fractions (x1, x2, x3) are identified: methanol (10, 30, 70 mol %), ethanol (7, 15, 60 mol %), 1-propanol (2, 10, 50 mol %), and 2-propanol (2, 10, 50 mol %). Above compositions of x1 no isolated alcohol molecules exist, and below x1 the formation of large hydration shells around the hydrophobic moieties of the alcohol is favored. The maximum number of water molecules, N0, in the hydration shell surrounding a single alcohol molecule increases with the length of the carbon chain of the alcohol. At x2 the greatest nonideality of the liquid structure exists with the formation of extended hydrogen bonded networks between alcohol and water molecules. The terahertz data show the maximum absorption relative to that predicted for an ideal mixture at that composition, while the PFG-NMR data exhibit a minimum in the alkyl chain self-diffusivity at x2, showing that the alcohol has reached a minimum in diffusion when this extended alcohol-water network has reached the highest degree of structuring. At x3 an equivalence of the alkyl and alcohol hydroxyl diffusion coefficients is determined by PFG-NMR, suggesting that the molecular mobility of the alcohol molecules becomes independent of that of the water molecules.

Quantitative magnetic resonance micro-imaging methods for pharmaceutical research

The use of magnetic resonance imaging (MRI) as a tool in pharmaceutical research is now well established and the current literature covers a multitude of different pharmaceutically relevant research areas. This review focuses on the use of quantitative magnetic resonance micro-imaging techniques and how they have been exploited to extract information that is of direct relevance to the pharmaceutical industry. The article is divided into two main areas. The first half outlines the theoretical aspects of magnetic resonance and deals with basic magnetic resonance theory, the effects of nuclear spin-lattice (T(1)), spin-spin (T(2)) relaxation and molecular diffusion upon image quantitation, and discusses the applications of rapid magnetic resonance imaging techniques. In addition to the theory, the review aims to provide some practical guidelines for the pharmaceutical researcher with an interest in MRI as to which MRI pulse sequences/protocols should be used and when. The second half of the article reviews the recent advances and developments that have appeared in the literature concerning the use of quantitative micro-imaging methods to pharmaceutically relevant research.

Interpretation of NMR Relaxation as a Tool for Characterising the Adsorption Strength of Liquids inside Porous Materials

Nuclear magnetic resonance (NMR) relaxation times are shown to provide a unique probe of adsorbate–adsorbent interactions in liquid-saturated porous materials. A short theoretical analysis is presented, which shows that the ratio of the longitudinal to transverse relaxation times (T1/T2) is related to an adsorbate–adsorbent interaction energy, and we introduce a quantitative metric esurf (based on the relaxation time ratio) characterising the strength of this surface interaction. We then consider the interaction of water with a range of oxide surfaces (TiO2 anatase, TiO2 rutile, γ-Al2O3, SiO2, θ-Al2O3 and ZrO2) and show that esurf correlates with the strongest adsorption sites present, as determined by temperature programmed desorption (TPD). Thus we demonstrate that NMR relaxation measurements have a direct physical interpretation in terms of the characterisation of activation energy of desorption from the surface. Further, for a series of chemically similar solid materials, in this case a range of oxide materials, for which at least two calibration values are obtainable by TPD, the esurf parameter yields a direct estimate of the maximum activation energy of desorption from the surface. The results suggest that T1/T2 measurements may become a useful addition to the methods available to characterise liquid-phase adsorption in porous materials. The particular motivation for this work is to characterise adsorbate–surface interactions in liquid-phase catalysis.

The distribution of water in degrading polyglycolide. Part II: Magnetic resonance imaging and drug release

This paper reports the use of magnetic resonance imaging (MRI) on polyglycolide disks to monitor the change in water ingress with degradation time. Very little response was measured before 13 days, but after this time, water began to penetrate the disks as fronts, starting from the sample surface and moving inwards towards the centre. These results provide more direct evidence in support of the four-stage degradation model for PGA outlined in previous literature, and in particular, that fairly sharp reaction-erosion fronts move in from the sample surface to the centre when the polymer is undergoing significant mass loss and water gain. A combination of MRI and drug release data suggest that fronts originate at the surface at about 7 (±2) days, and proceed at a rate of 0.033 (±0.002) mm/day. These results agree with results obtained from cumulative drug release profiles for different sample thicknesses presented in Part I. They support the hypothesis that drug releases quickly from the swollen regions behind the fronts where the polymer is open and porous, and that release finishes when the fronts meet in the centre of the sample.

The Degradation of Polyglycolide in Water and Deuterium Oxide. Part II: Nuclear Reaction Analysis and Magnetic Resonance Imaging of Water Distribution

Magnetic resonance imaging (MRI) and scanning microbeam nuclear reaction analysis (NRA) were used to monitor changes of water ingress into polyglycolide (PGA) disks with degradation time. MRI detects H2O, whereas NRA is sensitive to D2O. The acid-catalysed hydrolysis of the ester is significantly slower in D2O than H2O because of the kinetic isotope effect. This behaviour was investigated in Part I. In this paper, NRA was used to investigate PGA hydration in buffers made from D2O, and NRA and MRI experiments were performed on samples degraded buffers made from a 50% mixture of D2O and H2 O( D 2O/H2O 50:50) to allow a comparison between the two techniques. The NRA and MRI results provide direct evidence in support of the four-stage reaction ‐ erosion model reported in previous literature, and show that this model applies to polymer degradation in heavy water and in a buffer made from D2O/H2O 50:50. It is believed that this is the first time that NRA and MRI have been compared for the same hydrating system. q 2002 Elsevier Science Ltd. All rights reserved.

Quantifying Physics and Chemistry at Multiple Length-scales using Magnetic Resonance Techniques

Abstract Magnetic resonance (MR) is finding increasing use in chemical engineering research. The real power of MR techniques is that by bringing together spectroscopy, diffusion, micro-imaging and flow imaging, we have a non-invasive, chemically-specific measurement technique that can characterise a system over length-scales ranging from A to the cm-scale. The aims of this chapter are two-fold: first, to outline the principles of MR measurements such that they are presented as an integrated set of measurements clearly based on the same physicochemical phenomena; and second, to highlight the recent advances in the field, with a focus on the development of measurement techniques with immediate application to chemical engineering research. The power of bringing together the full range of MR measurements to address phenomena occurring over multiple length-scales is illustrated using examples taken from the field of chemical reaction engineering.

Direct visualization of in vitro drug mobilization from Lescol XL tablets using two-dimensional (19)F and (1)H magnetic resonance imaging.

This article reports the application of in vitro multinuclear ((19)F and (1)H) two-dimensional magnetic resonance imaging (MRI) to study both dissolution media ingress and drug egress from a commercial Lescol XL extended release tablet in a United States Pharmacopeia Type IV (USP-IV) dissolution cell under pharmacopoeial conditions. Noninvasive spatial maps of tablet swelling and dissolution, as well as the mobilization and distribution of the drug are quantified and visualized. Two-dimensional active pharmaceutical ingredient (API) mobilization and distribution maps were obtained via (19)F MRI. (19)F API maps were coregistered with (1)H T2-relaxation time maps enabling the simultaneous visualization of drug distribution and gel layer dynamics within the swollen tablet. The behavior of the MRI data is also discussed in terms of its relationship to the UV drug release behavior.

Electron-beam induced formation of nanoparticle chains and wires from a ruthenium cluster polymer

The novel organometallic cluster polymer of probable formula [Ru6C(CO)15Ph2PC2PPh2 ]n (n = ca. 1000) 1 has been prepared and, on irradiation in an electron beam, forms first nanoparticle chains and then conducting wires.

Assessing the effect of reducing agents on the selective catalytic reduction of NOx over Ag/Al2O3 catalysts

We gratefully acknowledge funding for this work from the EPSRC CASTech grant (EP/G012156/1). Carmine D’Agostino would like to acknowledge Wolfson College, Cambridge, for supporting his research activities. The authors would also like to thank Dr Jonathan Mitchell for useful discussions.