Investigation of mucoadhesive chitosan hydrogels containing tacrolimus as an immunosuppressant for the oral cavity

Immunosuppression is required in the oral cavity to combat difficult oral immunogenic diseases. Tacrolimus (FK 506) is a capable immunosuppressant to treat such ailments. Unfortunately, a great drawback is that systemically administered FK 506 exhibits several severe adverse drug reactions and thus a topical formulation is required. Due to lack of medicinal products with FK 506 on the market for treatment of the buccal area, different preparations were developed. Mucosa from porcine esophagus was used as a surrogate for buccal human mucosa due to their similar composition in the mucosa layer[1]. The formulations were prepared with chitosan as gelling agent and FK 506 as suspension gels. Sorbitol and glycerol as hygroscopic polyols were incorporated and the stability of hydrogels was investigated at different storage temperatures due to the possible impact on the acidic hydrolysis and thus stability of chitosan[2]. As reference formulation a HPMC paste containing a commercial tacrolimus ointment (Protopic®) was also produced. Exact tacrolimus concentration in the samples was measured by HPLC-UV/Vis. Resistance against saliva was tested by a mucoadhesion testing cell[3][4]. Furthermore, to compare ex vivo penetration, mucosa was incubated in Franz cells and dissected by a cryotome prior to tacrolimus quantification by HPLC-UV/Vis. During the stability studies it was shown that the chitosan hydrolysis was the slowest, the lower the storage temperature.