A QUALITY BY DESIGN APPROACH: FABRICATION, CHARACTERIZATION AND EVALUATION OF OPTIMIZED TRANSDERMAL THERAPEUTIC SYSTEM FOR ANTIRHEUMATIC LORNOXICAM.

ABSTRACT

Microemulsion was prepared using several concentrations of selected oil (pine oil), surfactant (cre- mophor RH40), co-surfactant (isopropanol) and water to improve bioavailability by increasing solubility and permeability of lomoxicam, which was then incorporated to carbomer 940 gel base to fabricate microemulsion based gel (MEBG) to sustained permeability for transdermal delivery. Initially, the formulations were investi- gated for physicochemical characteristics, i.e., pH, conductivity, viscosity, refractive index, zeta size, poly-dis- persity index and Atomic Force Microscopy. Also, the significance of the components on in vitro permeability was observed to find out optimum microemulsion (ME,) using Box-Behnken-Design (BBD). MEBG was com- pared for in vitro permeation, stability, skin irritation and anti-inflammatory studies using control gel and in vivo bioavailability study with oral tablet. Microemulsions exhibited the physiological pH (5.35-5.99), oil in water nature (139-185 tsiemens/cm), isotropic (1.3390-1.4166), narrow size (62 nm), homogeneity, Newtonian flow (52-160 centipoise) and spherical shape. Predicted values (Q2, flux, lag time) of optimized microemulsions derived from BBD were in reasonable agreement with experimental values. The formulations were stable and non-irritating to the skin. Significant difference was investigated when comparing percent inhibition of edema of MEBG (80%) and control gel (40%) with respect to standard. The MEBG behavior differed significantly from oral tablet formulation in vivo bioavailability. Such BBD based estimation will reduce time and cost in drug designing, delivery and targeting.