title: Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone.
abstract: The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (∼25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ∼75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ∼168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.
authors: Hytham H
authors: HH
authors: Gadalla
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.
authors: Ghareb M
authors: GM
authors: Soliman
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.
authors: Fergany A
authors: FA
authors: Mohammed
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.
authors: Ahmed M
authors: AM
authors: El-Sayed
mesh_terms: D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry*; D003106:Colon / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005782:Gels / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010368:Pectins / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011374:Progesterone / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D005782:Gels; D011374:Progesterone; D010368:Pectins; D048271:Chitosan; D015032:Zinc
keywords: Chitosan; Zn-pectinate; colon-targeting; microparticles; mucoadhesion; oral bioavailability; progesterone