Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486342 | Journal of Pharmaceutical Sciences | 2011 | 9 Pages |
Abstract
It is well known that the intestinal stability and absorption of protein drugs are improved when enzyme inhibitors/permeation enhancers are coadministered. Recently, it was hypothesized that an increased effectiveness of these adjuvants might be achieved by timing their release prior to that of the protein, so that a more favorable environment would be established in advance. Therefore, an oral system was proposed for twoâpulse colonic release of insulin and the protease inhibitor camostat mesilate/absorption enhancer sodium glycocholate. The device consisted of a drugâcontaining core, an inner swellable/erodible lowâviscosity hydroxypropyl methylcellulose (HPMC) coating, an intermediate adjuvant layer, and an additional outer HPMC coating. HPMC coats and camostat mesilate/sodium glycocholate films with differing thicknesses were applied to immediateârelease tablet cores by aqueous spray coating. The obtained units were characterized for weight, thickness, breaking force, and release performance. All systems showed satisfactory technological properties and the pursued pulsatile delivery behavior, with programmable delay phases preceding inhibitor/enhancer release and elapsing between inhibitor/enhancer and protein release, respectively. Indeed, both lag times linearly correlated with the relevant HPMC coating level. The system was thus proven suitable for yielding twoâpulse release profiles, in which lag phases could be modulated to provide convenient concentration patterns for proteins and adjuvants. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:3251-3259, 2011
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Maria Dorly Del Curto, Alessandra Maroni, Luca Palugan, Lucia Zema, Andrea Gazzaniga, Maria Edvige Sangalli,