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Characterization of the drug release process by investigation of its temperature dependence
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- Brohede, Ulrika (author)
- Uppsala universitet,Institutionen för teknikvetenskaper
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- Frenning, Göran (author)
- Uppsala universitet,Institutionen för farmaci
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- Strömme, Maria (author)
- Uppsala universitet,Institutionen för teknikvetenskaper
- (creator_code:org_t)
- Elsevier BV, 2004
- 2004
- English.
- In: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 93:7, s. 1796-1803
- Journal article (peer-reviewed)
Abstract
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- 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°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 ∼7.5 · 10−10 cm2/s, which is ∼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.
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