Sustained release of doxycycline as matrix metalloproteinase inhibitor for treatment of chronic periodontal diseases: in vitro evaluation

Abstract

A subantimicrobial dose of doxycycline is the only host response modifying, systemic therapy currently available for the treatment of periodontal disease. The purpose of this study was to develop and characterize a controlled-release delivery system of subantimicrobial dose doxycycline hyclate. Sustained release matrix tablets of doxycycline hyclate were developed using hydroxypropyl cellulose. The rate of doxycycline release from tablets was tested, erosion studies performed and the strength of the outer gel layer measured. The drug release mechanism was characterized using the combined data from the dissolution and erosion studies. The formulations studied were comprised from mixtures of hydrophilic polymers (hydroxypropyl cellulose) of high and low molecular weights in different ratios and in some cases contained a fraction of hydrophobic polymer. We found that the ratio of high molecular weight hydrophilic polymer content to low molecular weight hydrophilic polymer content determined whether the erosion process was the main mechanism governing drug release. In addition, we found that erosion constant value implied the governing release mechanism, since there was a 4-fold difference between erosion constant values in two different release mechanisms.