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Oral delivery system for two-pulse colonic release of protein drugs and protease inhibitor/absorption enhancer compounds.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 2011 Aug; Vol. 100 (8), pp. 3251-3259. Date of Electronic Publication: 2011 Apr 04. - Publication Year :
- 2011
-
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 two-pulse colonic release of insulin and the protease inhibitor camostat mesilate/absorption enhancer sodium glycocholate. The device consisted of a drug-containing core, an inner swellable/erodible low-viscosity 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 immediate-release 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 two-pulse release profiles, in which lag phases could be modulated to provide convenient concentration patterns for proteins and adjuvants.<br /> (Copyright © 2011 Wiley-Liss, Inc.)
- Subjects :
- Administration, Oral
Animals
Cattle
Colon metabolism
Drug Carriers chemistry
Drug Compounding
Drug Stability
Esters
Gabexate administration & dosage
Gabexate analogs & derivatives
Gabexate chemistry
Gabexate pharmacokinetics
Gabexate pharmacology
Glycocholic Acid administration & dosage
Glycocholic Acid chemistry
Glycocholic Acid pharmacology
Guanidines
Hypoglycemic Agents chemistry
Hypoglycemic Agents pharmacokinetics
Hypromellose Derivatives
Insulin chemistry
Insulin pharmacokinetics
Methylcellulose analogs & derivatives
Methylcellulose chemistry
Protease Inhibitors chemistry
Protease Inhibitors pharmacokinetics
Protease Inhibitors pharmacology
Solubility
Surface Properties
Tablets, Enteric-Coated
Viscosity
Colon enzymology
Drug Delivery Systems
Hypoglycemic Agents administration & dosage
Insulin administration & dosage
Intestinal Absorption drug effects
Protease Inhibitors administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6017
- Volume :
- 100
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 21465487
- Full Text :
- https://doi.org/10.1002/jps.22560