OPTIMIZATION OF GEL BASED SYSTEM OF LERCANIDIPINE BY STATISTICAL DESIGN FOR TRANSDERMAL DELIVERY; HISTOPATHOLOGICAL EXAMINATION AND RHEOLOGICAL CHARACTERIZATION

Our goal was to develop a transdermal gel formulation of lercanidipine by applying statistical approach for enhanced permeation and suitable application over skin. A 3-factors, 3-level Box-Behnken design were used to optimize the formulation. Ex vivo skin permeation studies were carried out to evaluate the responses such as flux, cumulative amount release in 24 hour and lag time using Franz-type diffusion cell. Confocal laser scanning microscopy (CLSM) of treated rat skin were used to assess the penetration ability and histopathological study was carried out in a quest to evaluate any skin irritation potential In vivo on rat skin and permeation mechanism of optimized Lercanidipine gel formulation after application over skin. Rheological characterization was carried out in order to clarify the suitability of optimized gel formulation for application over skin. The optimized formulation was having a composition of carbopol 934P (0.725%), soya lecithin (0.1%), and propylene glycol (15%).The skin permeation rate of lercanidipine significantly increased in proportion to the concentration of propylene glycol and lecithin while the gelling agent lay to decrease in skin permeation at higher level of it. Lag time has inverse relation with gelling agent and propylene glycol concentration. The result of CLSM study demonstrated significant penetration (>90μm) across rat skin while histopathological exa mination revealed the possible permeation mechanism by increasing cell gaps and rupturing of normal cell junction. This finding suggested a transdermal gel formulation of lercanidipine is having a good perspective to find effective formulation for transdermal drug release.