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Nasal administration of Carbamazepine using chitosan microspheres: in vitro/in vivo studies

Gavini, Elisabetta and Hegge, Anne Bee and Rassu, Gloria Maria Rita and Sanna, Vanna Annunziata and Testa, Cecilia and Pirisino, Gerolamo Antonio and Karlsen, Jan and Giunchedi, Paolo (2006) Nasal administration of Carbamazepine using chitosan microspheres: in vitro/in vivo studies. International Journal of Pharmaceutics, Vol. 307 (1), p. 9-15. ISSN 0378-5173. Article.

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DOI: 10.1016/j.ijpharm.2005.09.013

Abstract

The nasal route is used both for local therapies and, more recently, for the systemic administration of drugs, as well as for the delivery of peptides and vaccines. In this study the nasal administration of Carbamazepine (CBZ) has been studied using microspheres constituted by chitosan hydrochloride (CH) or chitosan glutamate (CG). Blank microspheres were also prepared as a comparison. The microspheres were produced using a spray-drying technique and characterized in terms of morphology (scanning electron microscopy, SEM), drug content, particle size (laser diffraction method) and thermal behaviour (differential scanning calorimetry, DSC). In vitro drug release studies were performed in phosphate buffer (pH 7.0). In vivo tests were carried out in sheep using the microparticles containing chitosan glutamate, chosen on the basis of the results of in vitro studies. The results were compared to those obtained after the nasal administration of CBZ (raw material) alone. For the evaluation of in vivo data statistical analysis was carried out using the unpaired t-test. Spray-drying was a good technique of preparation of CBZ-loaded microspheres. The loading of the drug into the polymeric network always led to an increase in the dissolution rate compared to CBZ raw material. The microspheres obtained using chitosan glutamate had the best behaviour both in vitro and in vivo. They increased the drug concentration in the serum when compared to the nasal administration of the pure drug (Cmax 800 and 25 ng/ml for microspheres and pure drug, respectively). The results obtained indicate that the loading of CBZ in chitosan glutamate microspheres increases the amount of the drug absorbed through the nose.

Item Type:Article
ID Code:606
Status:Published
Refereed:Yes
Uncontrolled Keywords:Carbamazepine, chitosan salts, spray-dried microspheres, nasal route, in vivo study, sheep
Subjects:Area 03 - Scienze chimiche > CHIM/09 Farmaceutico tecnologico applicativo
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Istituto zooprofilattico sperimentale della Sardegna, Sassari
001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:Elsevier Science
ISSN:0378-5173
Copyright Holders:© 2005 Elsevier
Deposited On:18 Aug 2009 10:02

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