Designing, Creating, and Assessing a Modified Pulsincap Delivery System for Intestine Targeting of Fluvastatin in Accordance with Circadian Rhythm

Abstract

The current study’s objective remains to create the Pulscap delivery system using an insoluble capsule core that contains fluvastatin sodium microspheres. Eudragit RL 100 polymer fluvastatin sodium microspheres were made using the solvent evaporation method. To reduce the possibility of stomach upset, these microspheres were hand-filled into capsules, plugged with hydrogel plugs, then sealed with ethyl cellulose acetate and dipped in an eight: two (vol/vol) Acetone: ethanol solution by butyl pthalate of (0.75%) and 5% cellulose acetate phthalate solution. Formulated dosage form was assessed for in-vivo X-ray imaging studies, in-vitro drug release studies, and in-vivo imaging studies, 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. A Pharmacodynamics study was also performed on lipid profiles in six groups of rabbits. Optimized formulation (F20) which is prepared with a drug and polymer ratio of 1:3, is selected based on a dissolution study which shows a percentage release of 99.98. ± 0.12% at 17th hour. In the in-vivo study, the plasma concentration at 12th hour 53.8 ± 0.02% and at 32nd hour 13.9 ± 0.05%. Pharmacokinetic parameter Cmax (ng/mL): 53.8 ± 0.41, MRT (h): 20.0 ± 0.14, t1/2 (h): 8.52 ± 0.014, Kel (h-1) :0.08 ± 0.014, Ka (h-1):0.25 ± 0.02, AUC0-a (ng h/mL): 944.9. ± 4.05. Serum lipid profile in high cholesterol rabbit after treatment with F20 formulation total cholesterol:240.83 ± 19.76, HDL-C:37.33 ± 2.16, triglycerides:318.67 ± 7.74, VLDL-C:63.73 ± 1.55, LDL-C:139.77 ± 18.74. Compared to lovastatin SR release, lovastatin pulsatile release, and fluvastatin SR release, the results imply that the F20 formulation’s pulsatile drug delivery has established good drug delivery for medications entering the gastrointestinal tract, and it displays superior pharmacokinetic and pharmacodynamic parameters.