PII S0730-725X(98)00021-6 ● Short Communication SELF-DIFFUSION AND MOLECULAR MOBILITY IN PVA-BASED DISSOLUTION- CONTROLLED SYSTEMS FOR DRUG DELIVERY J.E.M. SNAAR,* R. BOWTELL,* C.D. MELIA,† S. MORGAN,† B. NARASIMHAN, AND N.A. PEPPAS‡ *Magnetic Resonance Centre, Department of Physics and †Department of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham, UK; and ‡School of Chemical Engineering, Purdue University, West Lafayette, Indiana, USA Nuclear magnetic resonance (NMR) microscopy has been used to monitor the hydration of poly(vinyl alcohol) (PVA) samples of varying molecular weight. One-dimensional profiles weighted to predominantly show the variation of water concentration were acquired every 3 min during the first 30 min of hydration and subsequently at 1 and 2 h. Diffusion-weighted profiles obtained after 30 min and 1 and 2 h were used to calculate the spatial variation of the water self-diffusion coefficient. The resulting data provide supporting evidence for the hypothesis that phenomena such as reptation are important near the glassy/rubbery interface of polymers during dissolu- tion, while the diffusion gradually changes to Zimm type near the rubbery/solvent interface. © 1998 Elsevier Science Inc. Keywords: NMR microscopy; Poly(vinyl alcohol); Hydration; Diffusion; Reptation. INTRODUCTION Numerous controlled-release systems are based on poly- mers that swell and dissolve in the presence of a biolog- ical fluid. Dissolution of the carrier of such systems can be analysed in terms of a physical process consisting of transformation of the glassy polymer into a rubbery one, followed by chain disentanglement at the polymer sol- vent interface. 1 Understanding this process and the re- sulting polymer swelling allows for better characterisa- tion of the likely process of drug release in these systems. Nuclear magnetic resonance (NMR) microscopy is a powerful, non-destructive technique for monitoring the hydration of controlled-release systems 2,3 yielding infor- mation on the spatial and temporal variation of the state and concentration of water within the polymer. In this study, the hydration of one dissolution-controlled sys- tem, poly(vinyl alcohol) (PVA), was studied using an 11.7 T NMR microscope. EXPERIMENTAL METHODS Flat-faced tablets of 4.2-mm diameter and approxi- mately 2-mm thickness were prepared using PVA (Elva- nol grades 9050, 8582, HV, 133K supplied by DuPont) with four different average molecular weights (35,740, 48,240, 64,000 and 133,000). The tablets were formed by compression and subsequent machining of powder (par- ticle size 200 – 800 m), which was produced from cast polymer films. The films were subjected to a freeze/thaw process, which ensured that the degree of crystallinity in all samples was less than 5%. Each tablet was fixed onto a 4.2-mm diameter Nylon plug using cyanoacrylate ad- hesive. The plug was then glued inside a 5-mm NMR tube, with both the PVA tablet and Nylon making a tight fit inside the tube. Just before imaging, approximately 0.28 mL of distilled water was poured onto the surface of the tablet, forming a surface layer initially of about 5-mm depth. Address correspondence to Dr. R. Bowtell, Magnetic Resonance Centre, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. E-mail: richard.bowtell@nottingham.ac.uk Current address for B. Narasimhan: Department of Chem- ical and Biochemical Engineering, Rutgers University, Brett and Bowser Roads, Piscataway, NJ 08855-0909, USA Magnetic Resonance Imaging, Vol. 16, Nos. 5/6, pp. 691– 694, 1998 © 1998 Elsevier Science Inc. All rights reserved. Printed in the USA. 0730-725X/98 $19.00 + .00 691