title: Characterization of the drug release process by investigation of its temperature dependence.
abstract: Temperature-dependent drug release from disintegrating tablets made of NaCl-containing agglomerated micronized cellulose (AMC) granules has been studied to characterize the release process. Release measurements on tablets compacted at three different compaction pressures; 50, 100, and 200 MPa, were performed at seven different temperatures; 6, 23, 33, 43, 50, 55, and 63 degrees C using the recently developed alternating ionic current method. Tablets compacted at different compaction pressures showed similar release rates. The release process was found to be diffusion-controlled, and the activation energy of the diffusion coefficient was comparable to that obtained for diffusion in pure water. The results show that the AMC granules in contact with water swell to a size and shape that is only slightly affected by their compaction history and the ion diffusion operates mainly within liquid-filled pores within the AMC granules. By using the temperature dependence of the release process, it was possible to reach this conclusion without any assumptions concerning the number and radii of the granules into which the tablets disintegrated. Further, the magnitude of the effective diffusion coefficient was found to be approximately 7.5 x 10(-10) cm(2)/s, which is approximately four orders of magnitude lower than for unhindered diffusion of Na(+) and Cl(-) in water but similar to the diffusion coefficient for protons and OH(-) ions in microcrystalline cellulose.
authors.affiliation: Department of Engineering Sciences, The Angström Laboratory, Uppsala University, P.O. Box 534, S-751 21 Uppsala, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Brohede
authors.forename: Göran
authors.initials: G
authors.lastname: Frenning
authors.forename: Maria
authors.initials: M
authors.lastname: Strømme
mesh_terms: D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets