Turbulence Leads to Overestimation of the Acid-Diffusion Coefficient at Typical Experimental Conditions Using the Rotating Disk Apparatus

A rotating-disk apparatus (RDA) is used to determine the acid-diffusion coefficient. The equations to interpret RDA tests were previously derived assuming laminar flow to the disk, i.e. uniform accessibility with equal flux of the reactive species over the entire surface of the disk. Thus, the acid-diffusion coefficient is overestimated if the tests are run at transition or turbulent flow regimes. The present work validated laminar flow assumptions at typical RDA experimental conditions to optimize the acid-diffusion coefficient measurements. Disks of calcite marble with a diameter of 0.72, 1.11, and 1.46 in. were reacted in an RDA with hydrochloric acid at temperatures ranging from 73.4 to 100°F and disk rotational speeds ranging from 207 to 1,555 rpm. Transition to turbulent flow was observed at Reynolds numbers one order of magnitude lower than the universally accepted critical value of 3×105. Dissolution patterns on the disks after the experiments and the simulation results using a developed computational fluid-dynamics model confirm this conclusion. The turbulence created cavities near the edges of the 1.46 and 1.1 in. disks starting at rotational speeds of 587 and 829 rpm, respectively. The region of turbulent flow propagated toward the center of the disks with further increase of disk rotational speed. Because of the non-uniform (higher) mass-transfer rate, the diffusion coefficient is overestimated to a value of 6.71×10−5 and 5.01×10−5 cm2/s for the 1.46 and 1.11 in. disks, respectively. For the 0.72 in. disks, no turbulent flow was observed at all disk rotational speeds tested, and the calculated value of the diffusion coefficient was 3.08×10-5 cm2/s. Commercial RDA setups are often equipped with 1.0 or 1.5 in. coreholders and are capable of maintaining a disk rotational speed of up to 2,000 rpm. Thus, care must be taken not to run the tests at transition or turbulent flow regimes, as this will result in overestimation of the acid-diffusion coefficient. Preliminary results indicate that the observed phenomena also affect the RDA analysis of organic and other less reactive acid compositions. Presented results are integral for designing the RDA tests to improve the accuracy of the acid-diffusion coefficient calculations.

The Potential of Caffeic Acid Lipid Nanoparticulate Systems for Skin Application: In Vitro Assays to Assess Delivery and Antioxidant Effect

The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O2 concentration changes in the membrane induced by polyphenols and H2O2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin.

Enhanced Fluoride Bioavailability with Incorporation of Arginine in Child Dentifrices

Objective(s): To: 1) examine the fluoride concentrations in commercial child formula dentifrices (CFD)s; and 2) investigate the effect of arginine incorporation in CFDs on fluoride bioavailability. Study Design: Five commercial CFDs were examined for fluoride concentrations. Total, total soluble, and insoluble fluorides in CFDs were determined by the modified Taves acid-diffusion method (TAD). Ionic F and MFP were estimated by modified direct method with standard addition technique. L-arginine (L-Arg)/L-arginine monohydrochloride (L-Arg.HCl) were incorporated at 2% w/w in the commercial CFDs. The pH of the toothpaste slurries, buffer capacity of the added Arg, potentially available fluorides (PAF) and 1-min PAF by TAD were determined. Results: The CFDs had 4 to 32% of insoluble fluorides. Addition of L-Arg/L-Arg.HCl significantly improved the fluoride bioavailability in CFDs (p<0.05). Incorporation of L-Arg significantly increased the pH of toothpaste slurries (p<0.05); while L-Arg.HCl decreased the pH. Principal component analysis showed that L-Arg.HCl decreased the pH of toothpaste slurries due to the presence of Cl in the form of HCl; whereas the inherent elements/molecules (Na/P/Pi/F) remain distinct with unidentified influence on the variables. Conclusion(s): The CFDs containing NaF only have higher concentrations of bioavailable fluoride. Incorporating arginine (L-arginine or L-arginine monohydrochloride) at 2% w/w improves fluoride bioavailability of the child formula dentifrices.

Design and Characterization of Ethosomes for Transdermal Delivery of Caffeic Acid

The present investigation describes a formulative study aimed at designing ethosomes for caffeic acid transdermal administration. Since caffeic acid is characterized by antioxidant potential but also high instability, its encapsulation appears to be an interesting strategy. Ethosomes were produced by adding water into a phosphatidylcholine ethanol solution under magnetic stirring. Size distribution and morphology of ethosome were investigated by photon correlation spectroscopy, small-angle X-ray spectroscopy, and cryogenic transmission electron microscopy, while the entrapment capacity of caffeic acid was evaluated by high-performance liquid chromatography. Caffeic acid stability in ethosome was compared to the stability of the molecule in water, determined by mass spectrometry. Ethosome dispersion was thickened by poloxamer 407, obtaining an ethosomal gel that was characterized for rheological behavior and deformability. Caffeic acid diffusion kinetics were determined by Franz cells, while its penetration through skin, as well as its antioxidant activity, were evaluated using a porcine skin membrane–covered biosensor based on oxygen electrode. Ethosome mean diameter was ≈200 nm and almost stable within three months. The entrapment of caffeic acid in ethosome dramatically prolonged drug stability with respect to the aqueous solution, being 77% w/w in ethosome after six months, while in water, an almost complete degradation occurred within one month. The addition of poloxamer slightly modified vesicle structure and size, while it decreased the vesicle deformability. Caffeic acid diffusion coefficients from ethosome and ethosome gel were, respectively, 137- and 33-fold lower with respect to the aqueous solution. At last, the caffeic acid permeation and antioxidant power of ethosome were more intense with respect to the simple solution.