MUCOADHESIVE, SYRINGEABLE DRUG-DELIVERY SYSTEMS FOR CONTROLLED APPLICATION OF METRONIDAZOLE TO THE PERIODONTAL POCKET - IN-VITRO RELEASE KINETICS, SYRINGEABILITY, MECHANICAL AND MUCOADHESIVE PROPERTIES

Novel mucoadhesive formulations containing hydroxyethylcellulose (HEC; 3 and 5%, w/w) or Carbopol (3 and 5%, w/w), polycarbophil (PC; 1 and 3%, w/w) and metronidazole (5%, w/w) at pH 6.8 were designed for the t reatment of periodontal diseases. Each formulation was characterised i n terms of hardness, compressibility, adhesiveness and cohesiveness (u sing Texture Profile Analysis), drug release, adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode) and, finally, syringeability (using the texture analyser in com pression mode). Drug release from all formulations was non-diffusion c ontrolled. Drug release was significantly decreased as the concentrati on of each polymeric component was increased, due to both the concomit ant increased viscosity of the formulations and, additionally, the swe lling kinetics of PC following contact with dissolution fluid. Increas ing the concentrations of each polymeric component significantly incre ased formulation hardness, compressibility, adhesiveness, mucoadhesion and syringeability, yet decreased cohesiveness. Increased product har dness, compressibility and syringeability were due to polymeric effect s on formulation viscosity. The effects on cohesiveness may be explain ed both by increased viscosity and also by the increasing semi-solid n ature of products containing 5% HEC or Carbopol and PC (1 or 3%). The observations concerning formulation adhesiveness/mucoadhesion illustra te the adhesive nature of each polymeric component. Greatest adhesion was noted in formulations where neutralisation of PC was maximally sup pressed. For the most part, increased time of contact between formulat ion and mucin significantly increased the required force of detachment , due to the greater extent of mucin polymer hydration and interpenetr ation with the formulations. Significant statistical interactions were observed between the effects of each polymer on drug release and mech anical/mucoadhesive properties. These interactions may be explained by formulatory effects on the extent of swelling of PC. In conclusion, t he formulations described offered a wide range of mechanical and drug release characteristics. Formulations containing HEC exhibited superio r physical characteristics for improved drug delivery to the periodont al pocket and are now the subject of long-term clinical investigations . (C) 1997 Elsevier Science B.V.