Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule.

A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin's bioavailability and therapeutic effects.

Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles.

Gemcitabine-loaded solid lipid nanoparticles (SLNs) were produced by double emulsification technique using stearic acid as lipid, soy lecithin as surfactant and sodium taurocholate as cosurfactant. Prepared nanoparticles are characterized for particle size and surface morphology using scanning electron microscopy (SEM). Particle yield, entrapment efficiency and zeta potential were also determined. In-vitro release studies were performed in phosphate-buffered saline (PBS) pH 7.4 using metabolic shaker. The formulation F6 with maximum entrapment efficiency 72.42% and satisfactory in-vitro release was selected. In-vivo tissue distribution to liver, spleen, lung, heart and kidneys of optimized formulation followed by stability study under specific conditions were also determined. This investigation has shown preferential drug targeting to liver followed by spleen, lungs, kidneys and heart. Stability studies showed no significant change in the particle size followed with very slight decrease in entrapment efficiency at 25 ± 2 °C/60 ± 5% RH over a period of three months.

A propofol microemulsion with low free propofol in the aqueous phase: formulation, physicochemical characterization, stability and pharmacokinetics.

The purpose of this study was to develop a propofol microemulsion with a low concentration of free propofol in the aqueous phase. Propofol microemulsions were prepared based on single-factor experiments and orthogonal design. The optimal microemulsion was evaluated for pH, osmolarity, particle size, zeta potential, morphology, free propofol in the aqueous phase, stability, and pharmacokinetics in beagle dogs, and comparisons made with the commercial emulsion, Diprivan(®). The pH and osmolarity of the microemulsion were similar to those of Diprivan(®). The average particle size was 22.6±0.2 nm, and TEM imaging indicated that the microemulsion particles were spherical in appearance. The concentration of free propofol in the microemulsion was 21.3% lower than that of Diprivan(®). Storage stability tests suggested that the microemulsion was stable long-term under room temperature conditions. The pharmacokinetic profile for the microemulsion showed rapid distribution and elimination compared to Diprivan(®). We conclude that the prepared microemulsion may be clinically useful as a potential carrier for propofol delivery.

Stearic acid absorption and its metabolizable energy value are minimally lower than those of other fatty acids in healthy men fed mixed diets.

Compared with other saturated fatty acids, stearic acid appears to have different metabolic effects with respect to its impact on risk for cardiovascular disease. These differences may in part reflect biologically important differences in absorption. This study was designed to compare the absorption and the metabolizable energy value of stearic acid with other fatty acids from mixed diets fed to healthy humans. Healthy men (n = 11) were fed four diets with multiple fat sources that contained approximately 15% of energy (en%) from protein, 46 en% from carbohydrate and 39 en% from fat with 8 en% substitution across diets of the following: trans monoenes, oleic acid, saturated fatty acids (lauric + myristic + palmitic) or stearic acid fed as triacylglycerides. Fats were incorporated into mixed diets comprised of foods typically consumed in the United States. After a 14-d adaptation period, volunteers collected all feces for 7 d. Across diets, absorption of stearic acid (94.1 +/- 0.2%) was lower (P < 0.0002) than that of palmitic acid (97.3 +/- 0.2%) and higher than generally reported. Absorption of lauric, myristic, oleic, linoleic and trans 18:1 monoenes did not differ from each other (>99%) but was higher than that of stearic and palmitic acids (P < 0.001). Metabolizable energy values were similar for all fatty acids. Although absorption of palmitic and stearic acids was affected by diet treatment, the magnitudes of the differences were small and do not appear to be biologically important, at least in terms of lipoprotein metabolism. On the basis of these results, reduced stearic acid absorption does not appear to be responsible for the differences in plasma lipoprotein responses to stearic acid relative to other saturated or unsaturated fatty acids.

Preparation and evaluation of a melt pelletised paracetamol/stearic acid sustained release delivery system.

The potential of a sustained release formulation for paracetamol produced by melt pelletisation was investigated. The chosen formulation was based on the combination of stearic acid as a melting binder and anhydrous lactose as a filler. After determination of the size distribution, the pellet characterisation included scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), specific surface area and true density determination. Hence, the in vitro release from every single size fraction (2000, 1250, 800, 630, <630 microm) was evaluated and the release mechanism was analysed with the help of an appropriate mathematical model. The results of drug content and superficial atomic composition were found to be constant in all pellets size fractions, attesting the ability of melt pelletisation in a high shear mixer to form a product with homogeneous composition. The mathematical model is built on the hypotheses that drug diffusion and solid drug dissolution in the release environment are the key phenomena affecting drug release kinetics. Smaller classes apart (particles are not perfectly spherical), the comparison between model best fitting and experimental data indicated the reasonability of these hypotheses. Moreover, model reliability is proved by its ability of predicting drug release from a known mixture of the above mentioned particles classes.

Roller compaction and tabletting of St. John's wort plant dry extract using a gap width and force controlled roller compactor. II. Study of roller compaction variables on granule and tablet properties by a 3(3) factorial design.

The purpose of this study was to investigate the influence of roller compaction parameters and the amount of magnesium stearate used in dry granulation on granule and tablet properties of a dry herbal extract from St. John's wort (Hypericum perforatum L.). Two different extract batches were blended with magnesium stearate and compacted using a gap width and force controlled roller compactor. A 3(3) factorial design was used to evaluate the influence of the three independent variables, the amount of magnesium stearate, the roller compaction force, and the granulating sieve size on the mean particle size of granulated extracts and on the disintegration time of tablets containing these granulated extracts. The evaluation was done by multilinear stepwise regression analysis. The mean particle size d50 (R2 > 0.9) of both compacted extracts increased with increasing compaction force and with granulating sieve size. The disintegration time of the tablets was mostly in the range 5-15 min and increased slightly with increasing magnesium stearate concentration in the compacted extract and with decreasing compaction force of the roller compaction. The incorporation of magnesium stearate into the granulated extract reduced its potential negative influence on the disintegration time, while maintaining its functionality as a lubricant.