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. self-microemulsifying 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, Self-microemulsifying drug delivery system etc.