Professor Anthony Clough

Water diffusion into cylindrical biodegradable monolithic depots fabricated from extruded mixtures of poly(dl-lactide) and a peptidic drug, goserelin, containing 20, 30 and 40% drug by weight has been studied using an ion beam analysis technique. A series of depots were immersed in a phosphate buffered saline/heavy water solution at 37 °C for times ranging from 1 h to 7 days. One-dimensional radial profiles showing the diffusion of water into the depots were produced at points along the length of the sample and, for some short immersion times, axial profiles were obtained for the cylinder ends. The changes in weight, radius, drug release and water uptake of the depots with time were also studied. Using the water uptake measurements the one-dimensional radial profiles were normalised. From appropriate one-dimensional profiles at the shorter times Fickian diffusion coefficients were obtained for initial water diffusion. The average radial diffusion coefficients were (1.07±0.22)×10−8 cm2 s−1 for the 20% drug-loaded depots, (1.54±0.27)×10−8 cm2 s−1 for the 30% drug-loaded depots and (2.00±0.83)×10−8 cm2 s−1 for the 40% drug-loaded depots—in the ratio of the drug loadings i.e. 2:3:4, implying the water associated with drug during its uptake into the monoliths. The axial diffusion coefficients were found to be of the same order of magnitude as the radial diffusion coefficients, in accord with this hypothesis. At longer times there is a subsequent non-Fickian increase in the water concentration profile. In the case of depots loaded with 40% by weight of goserelin, the substantial fraction of the hydrophilic drug released at times greater than one day is accompanied by a decrease in radius and a decrease in water concentration near the depot surface.

With the aim of characterizing polymer-based drug delivery systems a combination of Scanning MeV 3He microbeam Nuclear Reaction, Backscattering and Particle Induced X-ray Emission (PIXE) techniques has been developed. This, together with gravimetric and UV techniques has been applied to characterize both water infusion and drug effusion for three in-mouth polymer–drug systems. Preliminary results are presented from the exposure of polymers, containing drug at a level of 9% by weight of the dry polymer, to both pure water and a phosphate buffered saline solution at 37°C.

The diffusion of water into the developmental drug-release polymer addition cured silicone has been investigated using {sup 3}He ion scanning micro-beam techniques developed at the University of Surrey. Polymer samples loaded with 15% by weight of the drug chlorohexidine diacetate were immersed in a water based phosphate buffered saline solution for times of 1 hour, 1 day, 1 week and 1 month. The results showed that as the water diffused into the polymer it associated with the drug allowing its release by diffusion through the network formed by water filled pores. Future improvements to the techniques are discussed including the use of an array of CdZnTe detectors.

Preliminary results are presented on a measurement technique for determination of water penetration into fibre optic sensors under high pressure, high temperature conditions. Both fibre optic sensors and communication fibres were subjected to prolonged treatment in heavy water at temperatures up to 250°C and pressures of 40 bar. Deuterium penetration is measured by a nuclear reaction technique based on a 3He micro-focussed ion beam, which permits two-dimensional mapping of the deuterium penetration into cleaved fibres. Water penetration can be detected whilst still confined to the cladding, well before any optical effects become apparent, permitting prediction of likely fibre lifetime under down-hole conditions after realistic experimental times. © 2001 Elsevier Science B.V.

The use of a 3He ion micro-beam technique to study the ingress/diffusion of water into a planar fibre optic grade glass and a cylindrical drug-release polymer is described. One-dimensional concentration profiles showing the depth of water ingress were produced. The depth of penetration of water into the glass was measured by fitting a Gaussian function to the concentration profile. The ingress of water into the drug-release polymer was found to be Fickian and a cylindrical diffusion model used to obtain a diffusion coefficient. © 2003 American Institute of Physics.

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 H2O (D2O/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. © 2002 Elsevier Science Ltd. All rights reserved.