Cinnarizine loaded lipid based system: preparation, optimization and in-vitro evaluation

Abstract

Background and Aim: Cinnarizine (CNZ) a piperazine derivative with anti-histaminic activity and high affinity to H1 receptors is currently used for the treatment of cerebral arteriosclerosis, cerebral thrombosis, and subarachnoid hemorrhage. The aim of present investigation was to develop a lipid based system i.e. selfmicroemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of poorly water soluble CNZ. Materials and Methods: The solubility of CNZ in various oils was determined to identify the oil phase for the preparation of SMEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. A Pseudo-ternary phase diagrams were constructed at ambient temperature to identify the efficient self-microemulsifying region using a water titration method. The prepared formulations of SMEDDS were evaluated for their Robustness to dilution, emulsification time, drug loading efficiency, phase separation, droplet size, zeta potential, TEM etc. Result: The optimized SMEDDS formulation contained CNZ (25mg), Oleic acid (16.66%w/w), Tween 80 (55.55%w/w), Transcutol P (27.77%w/w). The optimized formulation of the CNZ loaded SMEDDS exhibited a complete in vitro release in 5min as compared with marketed formulation which had a limited dissolution rate. Conclusion: These results suggest the potential use of SMEDDS to improve the dissolution and hence oral bioavailability of poorly water soluble CNZ. Keywords––Bioavailability, Cinnarizine, Entrapment efficiency, Pseudoternary phase diagram, Selfmicroemulsifying drug delivery system etc.