Quantitative fast MRI studies of controlled release drug delivery systems

The thesis describes the development and use of ultra-fast MRI techniques to quantitatively characterise the dissolution process of controlled drug release dosage forms. Implementations and validations of two quantitative single shot RARE based magnetic resonance imaging (MRI) protocols are described. Quantitative T₂ (spin-spin relaxation time constant) and diffusion weighted single shot RARE images, both with acquisition time of less than 3 minutes, were achieved by preconditioning the standard RARE sequence with a hard pulse CPMG echo train or an alternating phase bipolar pulsed field gradient spin echo (APGSTE) diffusion sequence respectively. T₂-preconditoined RARE and diffusion-preconditioned RARE experiments were carried out on 5 phantoms with T₂ values between 29 – 2200 ms. The optimisation of the phase encoding start value (PESV) parameter in the MRI pulse sequence was carried out, and four centric phase encoding schemes were also investigated. Phantoms imaged using the conventional RARE phase encoding scheme under the optimal PESV value of -0.2, showed a percentage error difference of 11 % for absolute water concentration (C_wat) maps, and an error of 2 % in T₂. Similarly an error of less than 2 % in the molecular self diffusion coefficient (D) was found compared to the corresponding reference value. The two quantitative preconditioned RARE pulse sequences were then used to follow the dissolution of hydroxypropylmethyl cellulose (HPMC) in both static and flowing environments. Finally, a case study was carried out on a coated tablet for the purpose of examining tablet coating efficiency upon scale up, where a pilot scale coated tablet was compared to a lab scale coated tablet. Two quite different dissolution behaviours of the two types of tablets were observed.