Sustained buccal delivery of the hydrophobic drug denbufylline using physically cross-linked palmitoyl glycol chitosan hydrogels

Sustained buccal delivery of the hydrophobic drug denbufylline using physically cross-linked palmitoyl glycol chitosan hydrogels
January 2003
Lee Martin a, Clive G. Wilson a, Fariba Koosha b and Ijeoma F. Uchegbu a
a Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK
b GlaxoSmithKline, Harlow, Essex, UK
European Journal of Pharmaceutics and Biopharmaceutics, Volume 55, Issue 1, January 2003, Pages 35-45
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Abstract
A physically cross-linked palmitoyl glycol chitosan hydrogel has been evaluated as a controlled release system for the delivery of hydrophobic drugs via the buccal route. Samples of palmitoyl glycol chitosan (GCP) with diminishing hydrophobicity (GCP12>GCP11>GCP21) were synthesized, characterized by 1H nuclear magnetic resonance and hydrogels prepared by freeze-drying an aqueous dispersion of the polymer in the presence of a model hydrophobic drug denbufylline and in some cases the soluble detergent sodium glycodeoxycholate (GDC). GDC was employed as a penetration enhancer. Gels were analysed for hydration, erosion, mucoadhesion and imaged by scanning electron microscopy. The buccal absorption of denbufylline from GCP12, denbufylline, GDC (20:12:1.5) formulations was also investigated in the rabbit model with Carbopol 974NF (CP), denbufylline, GDC (60:36:4) tablets used as controls. Denbufylline reduced the porosity, erosion and hydration of the gels while GDC increased the hydration and erosion. All gels were mucoadhesive but less so than the control CP tablets. Denbufylline was detected 0.5 h after dosing with the GCP12 formulation and delivery was sustained for at least 5 h after dosing. In comparison delivery from the CP tablets was not sustained and was first detected 1 h after dosing.