Factorial Design Studies and Biopharmaceutical Evaluation of Simvastatin Loaded Solid Lipid Nanoparticles for Improving the Oral Bioavailability

Abstract

Statins are HMG-CoA reductase inhibitors, which lower the cholesterol level through reversible and competitive inhibition; they are involved in the biosynthesis of cholesterol and other sterols. Simvastatin exhibits poor oral bioavailability (<5%) and undergoes extensive microsomal metabolism by CYP enzymes. CYP3A4 is the major metabolizing enzyme that metabolizes lactone form of simvastatin and significantly lowers intestinal uptake. The hydrophobic properties of simvastatin prevent complete dissolution of the drug in the intestinal fluid which also contributes to its lower bioavailability. SLNs are alternative carrier system to polymeric nanoparticles. SLNs are in submicron size range (1–1000 nm). To overcome the hepatic first pass metabolism and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited. In the present study, attempt has been made to prepare solid lipid nanoparticles of simvastatin to improve the bioavailability. SLNs of simvastatin were prepared with Trimyristin by hot homogenization followed by ultrasonication method. The SLNs were characterized for various physicochemical properties and analytical techniques like PXRD, DSC to study thermal nature and morphology of formulation and excipients. Promising results of the study indicated the applicability of simvastatin solid lipid nanoparticles as potential tools for improvement of bioavailability of poorly soluble drugs.

Formulation, in-vitro and in-vivo pharmacokinetic evaluation of simvastatin nanostructured lipid carrier loaded transdermal drug delivery system

“…Column: reversed-phase C18 column (250 mm × 4.6 mm i.d., particle size-5 μm) Mobile phase: methanol: 2 mM ammonium acetate and 500 μl of 0.5% formic acid (80:20, v/v) Flow rate: 1.0 ml/min Injection volume: 5 μl Calibration curve (concentration in μg/ml on X-axis vs. peak area in % on Y-axis) was obtained for eight solutions of simvastatin by using trichloroacetic acid solution in the concentration ranging from 0.02 to 0.16 μg/ml which was determined at 238 nm and the regression value was found to be r 2 = 0.999. The unknown plasma drug concentration was determined by picking the unknown sample peak area and interpolated it to X-axis at each time interval [31][32][33][34][35][36][37].…”

“…From the individual plasma drug concentration versus time profile, the following parameters are determined like peak plasma concentration (C max ), time taken to attain peak plasma concentration (t max ), area under curve (AUC 0-t ), and (AUC 0-∞ ) were read directly. The other PK parameters like biological half-life (t 1/2 ) and mean residence time (MRT) were also calculated using PK solver software [30][31][32][33][34][35][36][37].…”

Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies

“…Vesicle size (nm) (Y 1 ), % entrapment efficiency (Y 2 ) and 100 % in vitro drug release at 24 h (Y 3 ) were selected as dependent variables. Values of variables and batch codes are shown in Tables 1 and 2 Design Expert Ò DX 8.0.7.1 trial version software was used for the generation and evaluation of statistical experimental design Krishnam Raju et al 2014). …”

“…Ethanol injection method was used to prepare liposomes Krishnam Raju et al 2014). An alternative method for producing single unilamellar vesicles (SUV) that avoids both sonication and exposure to high pressure is the ethanol injection technique described by Batzri and Korn.…”

Guided Bone Regeneration with Ammoniomethacrylate-Based Barrier Membranes in a Radial Defect Model

“…Simvastatin was gradually released over 72 hours under sink conditions, i.e., at the artificial testing conditions when the solubility of the drug in the tested medium does not limit the amounts released from a dosage form. Given a poor solubility of simvastatin (about 6 ppm at pH 6.8 (Krishnam [ 42 ])) and low lymph turnover at the vicinity of the defect, the release duration of simvastatin in vivo was expected to cover for a significant part of the trial period.…”