European Journal of Biomedical and Pharmaceutical Sciences

SOLID DISPERSION INDUCED CO-CRYSTALLIZATION FOR ENHANCED DISSOLUTION RATE OF NEBIVOLOL HYDROCHLORIDE: DEVELOPMENT OF RAPIDLY DISINTEGRATING TABLETS

Ola A. Elfahl*, Ebtessam A. Essa and Gamal M. El Maghraby

ABSTRACT

Nebivolol hydrochloride is an antihypertensive agent which is classified as class II drug. Its oral bioavailability is variable due to its poor dissolution and pre-systemic metabolism. The aim of this work was to enhance the dissolution rate of nebivolol hydrochloride both in saliva pH (pH 6.8) and in gastric conditions (pH 1.2). This was done with the goal of developing fast disintegrating tablets with subsequent rapid dissolution. This was achieved by co-grinding of the drug with citric and/or tartaric acid before loading these mixtures in poloxamer by solid dispersion. The resulting dispersion was adsorbed on the solid surface of aerosil. The prepared systems were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction in addition to dissolution testing. Co-grinding and solid dispersion developed new crystalline structure of co-crystals type. The developed co-crystals liberated nebivolol at significantly higher dissolution rate. Optimum formulations were prepared as rapidly disintegrating tablets. The developed tablets underwent rapid disintegration with subsequent rapid dissolution of nebivolol. This was recorded irrespective to the pH of the dissolution medium. The developed tablets are thus suitable for intra-oral administration and can liberate most of the drug in the mouth for absorption through the buccal cavity. The formulations can also maintain rapid dissolution rate even after swallowing.

Keywords: Nebivolol, solid dispersion, poloxamer 407, citric acid, fast disintegrating tablet.