Nasal administration of metoclopramide from different dosage forms: in vitro, ex vivo, and in vivo evaluation

Authors: Tas, Cetin¹; Ozkan, Cansel Kose¹; Savaser, Ayhan¹; Ozkan, Yalcin¹; Tasdemir, Umut²; Altunay, Hikmet³

Source: Drug Delivery, Volume 16, Number 3, April 2009 , pp. 167-175(9)

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Abstract:

Nasal drug delivery is an interesting route of administration for metoclopramide hydrochloride (MTC) in preventing different kind of emesis. Currently, the routes of administration of antiemetics are oral or intravenous, although patient compliance is often impaired by the difficulties associated with acute emesis or invasiveness of parenteral administration. In this perspective, nasal dosage forms (solution, gel, and lyophilized powder) of MTC were prepared by using a mucoadhesive polymer sodium carboxymethylcellulose (NaCMC). In vitro and ex vivo drug release studies were performed in a modified horizontal diffusion chamber with cellulose membrane and excised cattle nasal mucosa as diffusion barriers. The tolerance of nasal mucosa to the formulation and its components were investigated using light microscopy. In vivo studies were carried out for the optimized formulations in sheep and the pharmacokinetics parameters were compared with oral solution and IV dosage form. The release of MTC from solution and powder formulations was found to be higher than gel formulation (p < 0.05). Histopathological examination did not detect any severe damage. Hydroxypropyl-β-cyclodextrin (HPβCD) used in powder formulations was found to be effective for enhancing the release and absorption of MTC. In contrast to in vitro and ex vivo experiments nasal bioavailability of gel is higher than those of solution and powder (p < 0.05). In conclusion, the NaCMC gel formulation of MTC with mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

Keywords: Nasal drug delivery; metoclopramide hydrochloride; gel; powder; cyclodextrin

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10717540902764172

Affiliations: 1: 1Gülhane Military Medical Academy, Department of Pharmaceutical Technology, Etlik, Ankara, Turkey 2: 2Lalahan Livestock Research Center Institute, Lalahan, Ankara, Turkey 3: 3Mehmet Akif Ersoy University, Faculty of Veterinary Medicine, Department of Histology and Embryology, Burdur, Turkey

Publication date: 2009-04-01

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Nasal administration of metoclopramide from different dosage forms: in vitro, ex vivo, and in vivo evaluation

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