Buccoadhesive slow-release tablets of acitretin: design and `in vivo' evaluation

Abstract

Acitretin is an aromatic retinoid used in the treatment of buccal keratinization disorders. The local therapy has recently shown promising results. The aims of this study were to develop buccoadhesive tablets with different `in vitro' release profiles of acitretin in order to select the types of tablets to be tested `in vivo', to determine the saliva acitretin concentration and to verify the therapeutical efficacy. On the basis of preliminary in vivo studies the dose of 10 mg of acitretin was used. Ten different formulations of two-layer buccoadhesive tablets were considered. The inferior layer (10 mg of Carbopol® 934P:Methocel® K4M, 1:2) provided bioadhesive properties to all the tablets. The upper layer of all tablets was the slow-release matrix containing the acitretin. The release-controlling component was an hydroxypropylmethylcellulose (HPMC); lactose was used as soluble filler. Aiming to achieve a wide range of release rates, three types of HPMC with different viscosity grades were used. A good relation was found between the in vitro dissolution profile and the in vivo permanence of acitretin in the oral cavity, that was longer for the formulation containing 85% of Methocel® E5 than the formulation containing 45% of Methocel® E5. Both formulations permitted to obtain good clinical results.