An oromucosal bioadhesive suspension for prolonged release of clobetasol propionate

Purpose This work aimed to develop an oral formulation assuring both fast onset of action and prolonged release by combining the peculiarities of a solution to those of prolonged release mucoadhesive microparticles. Clobetasol propionate (CP) was selected as model drug since it is commonly administered to treat muco-cutaneous inflammatory disease. Materials and methods Mucoadhesive microparticles containing CP were prepared in a one-step process by a ionic gelation method using sodium alginate (ALG) as encapsulating agent and linear (Carbopol 934P, L-PAA) or crosslinked (Noveon AA-1, C-PAA) acrylic acid-based polymers as bioadhesive polymer. The effects of different types of acrylic polymer, ALG/acrylic acid-based polymer ratios (3:1 or 1:1) and spraying pressure (450 or 550 mBar) were elucidated by using a 23 factorial design. The mouthwash formulations were characterized in terms of morphology, micrometrics, mucoadhesion and CP penetrated into porcine cheek mucosal segments. For each response, a multiple regression and ANOVA were performed and the models were tested using the statistical factorial design. Results Well-formed and spherical microparticles were obtained combining ALG with both acrylic acid-based polymers. The particle size was influenced only by the spraying pressure (average diameter: 170 μm at 450 mBar and 50 μm at 550 mBar). The amount of mucin bounded to ALG/C-PAA and ALG/ L-PAA microparticles was significantly higher (p < 0.05) than those made of ALG. The loaded CP affected neither the particle size distribution, nor morphology. The amount of CP penetrated in porcine cheek mucosae was significantly higher when CP was encapsulated in mucoadhesive microparticles with respect to the drug solution at the same concentration after 6 hours from administration. In particular, the highest values were obtained by using the mixture ALG/L-PAA in the ratio 1:1. The microparticles sizing at about 50 μm resulted stable over time without evidencing aggregation issues. Conclusion The proposed oromucosal bioadhesive prolonged release suspension could permit a reduction of the administration frequency of CP in the oral cavity.