Bioavailability Of Lovastatin Research Articles

Preparation and Characterization of Chitosan/Fish Scale Collagen/Lovastatin Nanocomposites

In this study, a polymeric drug delivery system based on chitosan and fish scale collagen was fabricated in the nanometer size by the emulsification method for loading lovastatin drug—a poorly water soluble drug for the treatment of reduction of cholesterol concentration in blood. An interesting point of this work is using collagen extracted from fresh water fish scales. The characteristics, properties, morphology and drug release control ability of the chitosan/collagen/lovastatin nanocomposites were evaluated by Infrared spectroscopy (IR), Field emission scanning electron microscopy (FESEM), Dynamic light scattering (DLS) and Ultraviolet–Visible spectroscopy (UV–Vis) methods. The obtained results showed that the chitosan/collagen/lovastatin nanocomposites are in spherical shape with the size of particles ranged from 72.1 to 444.0 nm. The chitosan/collagen system can improve the solubility and bioavailability of lovastatin in simulated gastric and intestine fluids. The drug release mechanism from chitosan/collagen/lovastatin nanocomposites was complied with the Korsmeyer-Peppas model. In addition, the in vivo test on mice of chitosan/collagen/lovastatin nanocomposites to investigate their toxicity was conducted and discussed.

Nanoparticles of Lovastatin: Design, Optimization and in vivo Evaluation.

IntroductionThe aim of the study was to optimize the processing factors of precipitation–ultrasonication technique to prepare nano-sized particles of Lovastatin (LA) for enhancing its solubility, dissolution rate and in vivo bioavailability.MethodsLA nanoparticles (LANs) were prepared using precipitation–ultrasonication technique under different processing factors. LANs were characterized in terms of particle size, zeta potential and in vitro release. Stability studies at 4°C, 25°C and 40°C were conducted for optimum formulation. In addition, the in vivo bioavailability of the optimum formula was studied in comparison to a marketed product in white master rats.ResultsThe optimized LAN formula (LAN15) had particle size (190±15), polydispersity index (0.626±0.11) and a zeta potential (−25±1.9 mV). The dissolution study of the nanosuspensions showed significant enhancement compared with pure drug. After 50 min, only 20.12±1.85% of LA was dissolved while 99.1±1.09% of LA was released from LAN15. Stability studies verified that nanosuspensions at 4°C and 25°C showed higher stability with no particle growth compared to the samples studied at 40°C. In vivo studies conducted in rats verified that there was 1.45-fold enhancement of Cmax of LAN15 as compared to marketed tablets.ConclusionNanoparticle prepared by ultrasonication-assisted precipitation method is a promising formula for enhancing the solubility and hence the bioavailability of Lovastatin.

The characteristics and mechanism of co-administration of lovastatin solid dispersion with kaempferol to increase oral bioavailability

Lovastatin shows low bioavailability (lower than 5%) after oral administration because of the poor aqueous solubility and widely metabolized by CYP3A4.Lovastatin solid dispersion was designed to enhance the dissolution. The in vitro intestinal absorption study indicated an increase in the apparent permeability of different intestinal segments compared with crude lovastatin. In the range of 12.5–50 μg/ml, the absorption of both lovastatin and lovastatin solid dispersion were found to be a passive process in rat’s jejunum and ileum, but not endocytosis process. CYP3A4 inhibitor (ketoconazole) significantly increased the intestinal absorption of lovastatin and lovastatin solid dispersion. However, P-glycoprotein efflux inhibitor (verapamil) had little effect on them.The absolute bioavailability of lovastatin and lovastatin acid after oral administration of lovastatin solid dispersion were increased by about 2.01-fold and 1.40-fold than that of lovastatin suspension. The oral bioavailability of lovastatin and lovastatin acid after oral administration of lovastatin solid dispersion with 10 mg/kg kaempferol (CYP3A4 inhibitor) were increased about 3.79-fold and 2.51-fold than that of lovastatin suspension, and the absolute bioavailability of lovastatin was up to 33.0%.As a result, co-administration of lovastatin solid dispersion with kaempferol could be a promising delivery system to improve the oral bioavailability of lovastatin.

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association.

A drug-drug interaction (DDI) is a pharmacokinetic or pharmacological influence of 1 medication on another that differs from the known or anticipated effects of each agent alone.1 A DDI may result in a change in either drug efficacy or drug toxicity for 1 or both of the interacting medications.2 Pharmacokinetic DDIs result in altered absorption, distribution, metabolism, or excretion of a medication. A pharmacodynamic DDI occurs when 1 medication modifies the pharmacological effect of another in an additive, a synergistic, or an antagonistic fashion. It is estimated that ≈2.8% of hospital admissions occur as a direct result of DDIs.3 However, the actual incidence of hospitalization secondary to clinically significant DDIs is likely to be highly underestimated because medication-related issues are more commonly reported as adverse drug reactions. Complex underlying disease states also may make recognizing a DDI more challenging, further contributing to a lower reported incidence. The overall clinical impact of a DDI can range from mild to life-threatening. Therefore, not all DDIs require a modification in therapy. The variability in the clinical significance of a DDI depends on both medication-specific and patient-specific factors. Medication-specific factors include the individual pharmacokinetic characteristics of each medication implicated in the DDI (eg, binding affinity, half-life [t1/2]), dose of the medications, serum concentrations, timing and sequence of administration, and duration of therapy. Patient-specific factors include age, sex, lifestyle, genetic polymorphisms causing differences in enzyme expression or activity, and disease impairment affecting drug metabolism (eg, hepatic or renal impairment, cardiac failure) or predisposition to differences in efficacy or safety (eg, statin intolerance in patients with a history of myopathy). Clinically significant DDIs are usually preventable. To optimize patient safety, healthcare providers must have an understanding of the mechanisms, magnitude, and potential consequences of any given DDI. Interpreting this information …

Enhanced solubility and bioavailability of lovastatin using stabilized form of self-emulsifying drug delivery system

Abstract Lovastatin (LVS) is a very popular HMG-CoA reductase inhibitor. Despite its popularity, bioavailability is very less ( The RSM analysis predicted that SA was highly significant (p

Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: Physicochemical characterization and pharmacokinetics

Nanostructured lipid carriers (NLCs) made from mixtures of Precirol and squalene were prepared to investigate whether the bioavailability of lovastatin can be improved by oral delivery. The size, zeta potential, drug-loading capacity, and release properties of the NLCs were compared with those of lipid nanoparticles containing pure Precirol (solid lipid nanoparticles, SLNs) and squalene (lipid emulsions, LEs). Stable nanoparticles with a mean size range of 180–290 nm and zeta potential range of −3 to −35 mV were developed. More than 70% lovastatin was entrapped in the NLCs and LEs, which was significantly higher compared to the SLNs. The in vitro release kinetics demonstrated that lovastatin release could be reduced by up to 60% with lipid nanoparticles containing Myverol as the lipophilic emulsifier, which showed a decreasing order of NLCs > LEs > SLNs. Drug release was further decreased by soybean phosphatidylcholine (SPC) incorporation, with NLCs and SLNs showing the slowest delivery. The oral lovastatin bioavailability was enhanced from 4% to 24% and 13% when the drug was administered from NLCs containing Myverol and SPC, respectively. The in vivo real-time bioluminescence imaging indicated superior stability of the Myverol system over the SPC system in the gastric environment.

Solubility Enhancement of Lovastatin by Modified Locust Bean Gum Using Solid Dispersion Techniques

The aim of the present study was to improve the solubility of poorly water soluble drug lovastatin (LS) by solid dispersion (SD) techniques using modified locust bean gum (MLBG) as a carrier. The locust bean gum (LBG) was modified by heating and there observed irreversible decrease in viscosity, whereas swelling property remains unaffected. The advantage of modification of LBG was illustrated by difference in dissolution profiles of their SD. Effect of polymer concentration and methods of preparation on solubility enhancement were studied using solubility and dissolution studies, respectively. The result of solubility study showed increase in solubility of LS with increase in concentration of MLBG. It was found that the dissolution rate of LS from its SD was dependent on the method of preparation of solid dispersions. Dissolution study revealed that the modified solvent evaporation is most convenient and effective method for solubility enhancement of poorly water soluble drug LS, among various methods of preparation of SD. The prepared SDs were characterized by differential scanning calorimetry, scanning electron microscopy, and X-ray diffraction study. In vivo study was performed by measuring 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG Co-A) reductase inhibition activity. Significant reduction in HMG Co-A reductase activity was observed in case of solid dispersions of LS than plain LS. In conclusion, MLBG could be used as a potential carrier in enhancing the dissolution rate and bioavailability of LS.