Controlled delivery of metronidaziole and doxycycline to periodonal pocket using bioadhesive polymers: Formulation consideratiions

Abstract

In the present investigation, mucoadhesive gel formulations of metronidazole and doxycycline in combination, were prepared using carboxymethylcellulose (CMC), methylcellulose (MC),  hydroxyethylcellulose (HEC), polyvinylpyrrolidone (PVP)
polycarbophil (PC) and poloxamer. Each formulation was characterized in terms of polarizing light microscopy, hardness, compressibility, adhesiveness, cohesiveness, syringeability, adhesion to a mucin disc and drug release. Addition of CMC and PVP to the gel favored hexagonal phase formation. Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion and syringeability, yet decreasing cohesiveness. Increased time of contact between formulation and mucin significantly increased the required force of detachment. Drug release from all formulations was non-diffusion controlled and significantly decreased as the concentration of polymer was increased, due to concomitant increased viscosity of the formulations and the swelling kinetics of PC following contact with dissolution fluid. Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations.