title: Nasal absorption of metoclopramide from different Carbopol 981 based formulations: In vitro, ex vivo and in vivo evaluation.
abstract: There is a need for nasal drug delivery of metoclopramide HCI (MTC) in specific patient populations where the use of commercially available intravenous and oral dosage forms may be inconvenient and/or unfeasible. In this perspective, nasal dosage forms (solution, gel and lyophilized powder) of MTC were prepared by using a mucoadhesive polymer Carbopol 981 (CRB 981). The drug release studies of formulations were performed by using a modified horizontal diffusion chamber with cellulose membrane and excised cattle nasal mucosa as diffusion barriers. After the ex vivo experiments, the morphological appearances of the nasal mucosa were analyzed with the light microscopic studies. In vivo experiments were carried on sheep model. The release of MTC from solution and powder formulations was found higher than gel formulation (p < 0.05) and no severe damage was found on the integrity of nasal mucosa after ex vivo experiments. The penetration enhancing effect of dimethyl-beta-cyclodextrin (DM-beta-CD) used in powder formulations was observed in ex vivo and in vivo experiments. In contrast to in vitro and ex vivo experiments the nasal bioavailability of gel formulation was found higher than those of the solution and powder (p < 0.05) and might represent a promising novel tool for the systemic delivery of MTC.
authors.affiliation: Gülhane Military Medical Academy, Department of Pharmaceutical Technology, Etlik-Ankara, Turkey.
authors.forename: Cetin
authors.initials: C
authors.lastname: Tas
authors.forename: Cansel Kose
authors.initials: CK
authors.lastname: Ozkan
authors.forename: Ayhan
authors.initials: A
authors.lastname: Savaser
authors.forename: Yalcin
authors.initials: Y
authors.lastname: Ozkan
authors.forename: Umut
authors.initials: U
authors.lastname: Tasdemir
authors.forename: Hikmet
authors.initials: H
authors.lastname: Altunay
mesh_terms: D000042:Absorption / Q000502:physiology; D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005782:Gels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008787:Metoclopramide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D011208:Powders; D012756:Sheep; D012996:Solutions; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000180:Acrylic Resins; C516894:Carbopol 981; D018492:Dopamine Antagonists; D005782:Gels; D011208:Powders; D012996:Solutions; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D008787:Metoclopramide