Formulation and in-vitro evaluation of Liquid and solid self microemulsifying Drug delivery system of pitavastatin Calcium

In the present study, an attempt has been made to develop Self Micro Emulsifying Drug Delivery system of Pitavastatin in order to enhance the solubility and dissolution rate by incorporating the drug in a lipid vehicle. The results of compatability studies by Infrared spectroscopy and differential scanning calorimetry (DSC), showed no interaction between the drug and excipients. Various oils, surfactants and co-surfactants are optimized based on their solulbilising capacity and % transmittance values. The solubility of Pitavastatin was found to higher in oleic acid (97.89%±0.06) and Capryol 90 (93.69%±0.31) Pseudo ternary phase diagrams were constructed to get the maximum self emulsification region of SMEDDS, and the optimum concentration of oil was found to be 10-50% and Smixture was found to be 50-90% for both oils. Two different type of Pitavastatin liquid SMEDDS were successfully prepared at different ratios of oil, surfactant and co-surfactant by simple admixing method, namely CF1-CF9 and OF1-OF9. The prepared SMEDDS were evaluated for their physiochemical parameters. (Dispersibility test, visual assessment, self emulsification time, % transmittance and Refractive index). The RI of formulation ranges from 1.333 to 1.348. The % transmittance value for all the formulation ranges from 68 -97%. And the formulation which shown % transmittance value of above 90% provides clear emulsion. CF8 and OF8 shows maximum % transmittance (97.47±0.18% and 94.28±0.22%) The drug content of liquid SMEDDS ranges from 92-98%. Formulation CF8 and OF8 shown maximum drug content. (98.02±0.07% and 98.23±0.17% respectively). Then the liquid SMEDDS were converted into S-SMEDDS by adsorption technique by mixing it with Micro crystalline Cellulose at 1:1 w/w ratio. In vitro release study of all the formulations were shown an increased drug release. Dissolution rate of all the formulations were improved when compared to pure drug. The dissolution study was carried out in pH 6.8 buffer for 2 hours. The formulations shown higher rate of drug release than that of the pure drug and marketed formulation, and all formulations showed 60-82% of drug release within two hours. Formulation OF8 and CF8 shows 80.52±0.12% and 82.14±0.15% respectively, which is higher rate than the pure drug (59.25±0.20%) and conventional tablet (64.72±0.21%) Particle size analyzer used to explore the particle size of Pitavastatin SMEDDS showed a suitable particle size of 139.5 nm and 0.621nm for OF8 and CF8 respectively. The polydispersibility index of selected SMEDDS formulations (CF8 & OF8) were 0.377 and 0.291, which indicated a broad size distribution of particles. Zeta potential value of Pitavastatin SMEDDS showed a negative surface charge (- 23.9mv and -20.9mv). SEM studies confirmed the morphology of the solid SMEDDS. The crystalline state of the formulation was altered according to the XRPD analysis. It confirms the solubilisation of drug. CONCLUSION: Pitavastain is a poorly water soluble drug, and its bioavailability is only about 60% due it is poor solubility. When administering this poorly soluble compound with hydrophilic carriers will enhance the solubility of the drug. Hence, it was concluded that Self Micro Emulsifying drug delivery system is a good approach to enhance the solubility and dissolution property of Pitavastatin. The composition of optimized formulation [CF8 consist of Capryol 90 as oil(45%), Cremophore RH(41.2%) as surfactant and Propylene glycol(13.75%) as co-surfactant and OF8 consist of Oleic acid (45%), Tween 80 (41.2%) and Propylene glycol (13.75%)] containing 4mg of Pitavastatin calcium showing drug release for solid SMEDDS formulation (82.14% & 80.52%), Particle size (139.5 nm & 621.3nm), Zeta potential (-23.29 & -20.9), viscosity (0. 8824 cP). In-vitro drug release of the C8 and OF8 was highly significant compared to pure drug and marketed conventional tablet. Here the liquid SMEDDS are successfully converted into solid SMEDDS using MCC by adsorption technique.