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

Nasal administration of Carbamazepine using chitosan microspheres: In vitro/in vivo studies
Received 6 June 2005; revised 5 September 2005; accepted 24 September 2005. Available online 27 October 2005.
E. Gavinia, A.B. Heggeb, G. Rassua, V. Sannaa, C. Testac, G. Pirisinoa, J. Karlsenb and P. Giunchedia
International Journal of Pharmaceutics
Volume 307, Issue 1 , 3 January 2006
aDipartimento di Scienze del Farmaco, University of Sassari, via Muroni 23/a, 07100 Sassari, Italy
bInstitute of Pharmacy, University of Oslo, Oslo, Norway
cIstituto Zooprofilattico Sperimentale della Sardegna, Sassari, Italy
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.
Keywords: Carbamazepine; Chitosan salts; Spray-dried microspheres; Nasal route; In vivo study; Sheep

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