Solubility Enhancement of Atorvastatin Calcium Using Novel Technique

Solubility and dissolution characteristics of any drug are critical factors controlling its oral bioavailability. Disposition rate of poorly soluble, highly permeable (BCS-II) drugs like atorvastatin calcium can be enhanced by the use of the liquisolid (LS) method. Various liquisolid compacts were designed utilizing a mathematical model for estimation of necessary amounts of powder and liquid ingredients to yield an acceptably low and compressible mixture. Avicel PH 102, Aerosil 200 and Explotab were utilized as carrier, coating material and disintegrant, respectively. Prepared liquisolid systems were characterized for their micromeritic properties and potential drug-excipient interaction using Infrared spectra (IR) analysis, differential scanning calorimetry (DSC) and X- ray powder diffraction (XRPD). Liquisolid compacts were formulated and characterized for their tabletting property. The liquisolid system had good micromeritic properties. IR and DSC analyses eliminated any signiicant drug-excipient interaction. The XRPD analysis confirmed the formation of a solid solution within the compact matrix. The tabletting behavior of the liquisolid compacts was found to be within the acceptable range. Release rates of liquisolid compacts were significantly greater in comparison with directly compressed tablets, owing to improving wetting characteristics and drug surface area. From the derived pharmacokinetic parameters, like the AUC, tmax and Cmax, liquisolid compacts exhibited improved bioavailability than the conventional formulation. This research indicates that the liquisolid method is a good alternative for the enhancement of the dissolution and oral bioavailability of water insoluble drugs a confirmed by the estimation of the pharmacokinetic parameters in vivo in rabbits.