Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol.
BACKGROUND
Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application.


OBJECTIVE
Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion.


METHODS
Interaction between atenolol and randomly methylated beta-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release.


RESULTS
The formation of a stabile inclusion complex (K(s) = 783.4 +/- 21.6 M(-1)) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis.


CONCLUSIONS
Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery.
Jug
M
M
Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. mjug@pharma.hr
Bećirević-Laćan
M
M
Bengez
S
S
D000268:Adhesiveness; D000278:Administration, Buccal; D001262:Atenolol / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*
D003505:Cyclodextrins; D001262:Atenolol