Oral solid compritol 888 ATO nanosuspension of simvastatin: optimization and biodistribution studies.
The purpose of the present investigation was to develop solid lipid nanoparticles (SLNs) of simvastatin in order to enhance its oral bioavailability by minimizing its first-pass metabolism. To achieve our goal, SLNs were prepared by solvent injection technique and optimized by 2(3) full factorial experimental design using Design Expert software. The SLN formulations were optimized for amount of compritol, concentration of poloxamer, and volume of acetone in order to achieve desired responses of particle size, entrapment efficiency (EE), and cumulative drug release (CDR). Response surface plots were constructed to study the influence of each variable on each response and the interactions between any two variables were also analyzed. Formulation F(10) with particle size of 271.18 nm, % EE of 68.16% and % CDR of 76.23%, and highest desirability value of 0.645 was selected as optimized formulation. The optimized formulation was evaluated for biodistribution and pharmacokinetics by technetium-99m (Tc-99m) radiolabeling technique in mice. The relative bioavailability of simvastatin from optimized SLNs was found to be 220%, substantiating the protective action of SLNs against liver metabolism. However, though the drug initially bypassed the liver metabolism, simvastatin continuously entered in liver to exert its therapeutic action that was evidenced by biodistribution study.
Department of Pharmaceutics, Rajiv Academy for Pharmacy, National Highway #2, Mathura, Uttar Pradesh, India.
Mayank
M
Shah
Krishna
K
Chuttani
A K
AK
Mishra
Kamla
K
Pathak
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry*; D007553:Isotope Labeling; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D019821:Simvastatin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D005227:Fatty Acids; C086409:glyceryl behenate; D019821:Simvastatin