European Journal of Biomedical and Pharmaceutical Sciences

EFFECT OF ACIDIFIERS ON THE DISSOLUTION RATE OF DRONEDARONE: DEVELOPMENT OF ORO-DISPERSIBLE TABLETS

Maysa Hussien*, Ebtessam Essa, Gamal El Maghraby and Shaimaa Ashmawy

ABSTRACT

Dronedarone Hydrochloride is an antiarrhythmic agent that is commonly prescribed to treat atrial fibrillation. Unfortunately, it shows poor and erratic bioavailability owing to its limited aqueous solubility. The aim of this work was to improve Dronedarone Hydrochloride dissolution employing pH modulation approach. Being a weak basic compounnd, Dronedarone Hydrochloride was mixed with acidifiers to elucidate their effect on its dissolution behaviour. The work was extended to develop Oro-dispersible tablets to facilitate adminstration by geriateric patients. Dronedarone Hydochloride was physically mixed with different weak acids namely citric acid, succnic acid, tartaric acid and fumaric acid at 1:1 and 1:2 molar ratio (drug to acid, respectively). All acidifiers, apart from fumaric acid, markedly improved Dronedarone Hydochloride dissolution. The propmt release of about 72 %,58.9%, 72. 88% of the loaded dose after 5 minutes was obtained from equimolar blends of citric, succinic and tartaric acid, respectively, compared to only 13.7% from pure drug. The drug/acid physical mixtures were used to prepare tablets. The prepared Oro-dispersible tablets perserved the prompt drug release. This work provides simple stratigy for overcoming the dissolution problems of Dronedarone Hydochloride with a convenient means for drug adminstration.

Keywords: Fumaric acid, Tartaric acid, Succnic acid, Citric acid, Dronedarone Hydochloride, Fast disintegrating tablets.