A Novel Oromucosal Prolonged Release Mucoadhesive Suspension by One Step Spray Coagulation Method

Francesco      Cilurzo; Chiara G.M.      Gennari; Francesca      Selmin; Umberto M.      Musazzi; Cristiano      Rumio; Paola      Minghetti

Abstract

An oromucosal mucoadhesive suspension (OMS) able to combine the peculiarities of prolonged release mucoadhesive microparticles with those of an immediate release oromucosal solution is described. Microparticles were obtained by ionotropic gelation of alginate blended with another mucoadhesive material in a one step process where the cross-linking bath constituted the suspension vehicle. The effects of formulation and processing conditions on OMS performances were measured in-vitro determining the enhancement of drug penetration in buccal porcine mucosa and inhibition of tooth plaque formation using flurbiprofen and delmopinol as model drugs, respectively. Well-formed and spherical microparticles were obtained combining alginate with carbomer; linear dependence of particle size from the feed composition, viscosity and atomization pressure was found. As demonstrated by using FITC-labelled microparticles, the system remained onto the buccal mucosa at least for a six hour period. As a consequence, 0.1% flurbiprofen OMS guaranteed a concentration of flurbiprofen into buccal porcine mucosa over 6 hours comparable to 0.25% flurbiprofen reference solution, allowing a potential reduction of the 60% administered dose. The use of in-house made artificial mouth revealed that the once-a-day administration of 0.1% delmopinol OMS was as effective in plaque inhibition as the 0.2% delmopinol reference solution product given twice-a-day. These results suggested that the development of bioadhesive oromucosal suspensions, localizing the drug into buccal cavity, can reduce regimen and administrated dose.

Keywords: Alginate, delmopinol, flurbiprofen, ionic gelation, mucoadhesion.