Estimation Of Pharmacokinetic Parameters Of Lovastatin Pulsin Capsule In Albino Rabbits

Abstract

Aim: The aim of the present study is to develop Pulsincap delivery system using insoluble capsule body filled with Lovastatin microspheres.

Method: Lovastatin microspheres were prepared by solvent evaporation method using Eudragit FS30D polymer. These microspheres were hand filled in capsule followed by plugging with hydrogel plug and finally sealed with ethyl cellulose acetate and coated with dip coating with 5% cellulose acetate phthalate in 8.2 (v/v) mixture of acetone: ethanol plasticized with butyl phthalate (0.75%) to prevent variable gastric emptying. Formulated dosage form were evaluated for in-vivo X-ray imaging study, in-vitro and in-vivo drug release study. Pharmacokinetic study of the optimized formulation was conducted in a two way cross over design with 6 rabbits in each group and the pharmacokinetic parameters (Cmax, Ka, Ke, MRT and AUC0-α) are measured. Pharmacodynamics study was also performed on lipid profile in six groups of rabbits.

Results:Optimized formulation (F12) which is prepared with drug and polymer ratio of 1:3, is selected based on dissolution study which shows percentage release of 99.87±0.12% at 16th hour. In in-vivo study, the plasma concentration at 12th hour 52.51±0.02% and at 32nd hour 15.6 ±0.05%. Pharmacokinetic parameter Cmax (ng/ml): 52.1± 0.41, MRT (h): 21.7± 0.14, t1/2 (h) :8.07± 0.014, Kel (h-1) :0.08 ± 0.014, Ka (h-1) :0.19± 0.02, AUC0- (ng h/ml) :919.9.±4.05.Serum lipid profile in high cholesterol rabbit after treating with F12 Formulation Total Cholesterol:306.17±11.55, HDL-C:31.33±3.27, Triglycerides:337.50±11.02, VLDL-C:67.50±2.2, LDL-C:207.33±10.06.

Conclusion:The results suggest that the F12 formulation pulsatile drug delivery has positioned delivery of drugs into the gastrointestinal tract with excellent drug delivery compared to Fluvastatin SR release, Lovastatin SR Release, Lovastatin pulsatile release. And exhibits the better pharmacokinetic and pharmacodynamics parameter.