Relationships between solid dispersion preparation process, particle size and drug release: an NMR and NMR microimaging study
2010 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 76, no 2, 311-319 p.Article in journal (Refereed) Published
Solid dispersion tablets prepared by either spray drying or rotoevaporation and exhibiting different grain and pore sizes were investigated under the process of hydration-swelling-gelation. H-2 and H-1 NMR microimaging experiments were used to selectively follow water penetration and polymer mobilization kinetics, respectively, while the drug release kinetics was followed by H-1 NMR spectroscopy. The obtained data, in combination with morphological information by scanning electron microscopy (SEM), reveal a complex process that ultimately leads to release of the drug into the aqueous phase. We find that the rate of water ingress has no direct influence on release kinetics, which also renders air in the tablets a secondary factor. On the other hand, drug release is directly correlated with the polymer mobilization kinetics. Water diffusion into the originally dry polymer grains determines the rate of grain swelling and the hydration within the grains varies strongly with grain size. We propose that this sets the stage for creating homogeneous gels for small grain sizes and heterogeneous gels for large grain sizes. Fast diffusion through water-rich sections of the inhomogeneous gels that exhibit a large mesh size is the factor which yields a faster drug release from tablets prepared by rotoevaporation.
Place, publisher, year, edition, pages
2010. Vol. 76, no 2, 311-319 p.
Gel layer formation, Rotoevaporation, Spray drying, Hydroxypropyl methylcellulose, HPMC, Diffusion
IdentifiersURN: urn:nbn:se:kth:diva-24544DOI: 10.1016/j.ejpb.2010.06.006ISI: 000283756700021ScopusID: 2-s2.0-77957281261OAI: oai:DiVA.org:kth-24544DiVA: diva2:351697
QC 20100915. Uppdaterad från submitted till published (20101207).2010-09-152010-09-152010-12-07Bibliographically approved