1487 JPP 2003, 55: 1487–1493 ß 2003 The Authors Received February 27, 2003 Accepted July 18, 2003 DOI 10.1211/0022357022133 ISSN 0022-3573 Institute of Molecular Physics Polish Academy of Sciences, M. Smoluchowskiego 19, 60-179, Poznan, Poland Jadwiga Tritt-Goc, Joanna Kowalczuk, Narcyz Pislewski Correspondence: J. Tritt-Goc, Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznan, Poland. E-mail: jtg@ifmpan.poznan.pl Funding: We acknowledge financial support under Grant no.4 P05F 010 19 from the Polish Committee for Scientific Research. Magnetic resonance imaging study of the transport phenomena of solvent into the gel layer of hypromellose matrices containing tetracycline hydrochloride Jadwiga Tritt-Goc, Joanna Kowalczuk and Narcyz Pislewski Abstract Magnetic resonance imaging was used to study the diffusion of a water solution of hydrochloric acid into hypromellose (hydroxypropylmethylcellulose) matrices. Spatially resolved information was obtained about the self-diffusion coefficient and spin–spin relaxation time of solvent protons in the gel layer of hypromellose matrices loaded with different amounts of tetracycline hydrochloride. The data showed the influence of the drug concentration on the diffusion and spin–spin relaxation. Higher drug concentrations in the hypromellose matrix led to greater swelling of the matrix and faster diffusion of the water molecules inside the gel layer of the polymer. The observed differences between the radial and axial diffusion were interpreted in terms of the stresses imposed in the axial direction during the compression of the samples. The spin–spin and diffusion profiles indicated that the diffusion of a water solution of hydrochloric acid into hypromellose, pure and loaded with different amounts of tetracycline hydrochloride, was characterized as a Case II mechanism. Introduction Hypromellose (hydroxypropylmethylcellulose) is the most commonly used polymer in the production of controlled release, hydrophilic matrices. Thus, this polymer has been studied widely using different methods: electron microscopy and NMR spectroscopy (Melia et al 1992, 1994); an optical imaging technique (Gao et al 1996); a calorimetric technique (Colombo et al 1999); ultrasound method (Konrad et al 1998); gravimetrical technique (Michailova etal 2001); and by magnetic resonance imaging (MRI) (Snaar et al 2001; Tritt-Goc & Pislewski 2002; Kowalczuk et al. 2003). Those studies demon- strated that hypromellose swells while in contact with an aqueous liquid, dissolution medium or gastrointestinal fluid, and makes a continuous gel layer. The formation of the gel layer is the key parameter that controls the drug release from the matrix. The selected polymer must hydrate quickly enough to form a gel layer before the contents of the matrix tablet can dissolve. The matrix erosion (dissolution of the polymer) is also a rate-controlling factor in drug dissolution. However, for hypromellose and soluble drugs, the drugs may diffuse out of the gel before the dissolution of the polymer (Katzhendler etal 2000). The swelling behaviour of the hypromellose is controlled by the rate of its hydration in the aqueous liquid, which depends on the diffusion of the solvent molecules into hypromellose. Since the rate of the hypromellose swelling determines the kinetics of the drug release from this matrix we undertook measurements to study the diffusion of the water solvent into the polymer. In our experiments, the diffusion (also swelling of the matrix) was not restricted to one direction as in most experiments performed up to now, but was allowed in the radial and axial directions. The aim of the study was to determine the influence of the drug concentration on the diffusion and swelling, and therefore on drug release properties. We used tetracycline hydrochloride as a model drug, which is used widely in medicine as a broad-spectrum antibiotic. The state of the water within the gel layer of hydrated hypromellose matrices (pure and containing Downloaded from https://academic.oup.com/jpp/article/55/11/1487/6148256 by guest on 21 March 2024