Enhanced association of probucol with chylomicron by pharmaceutical excipients: an in vitro study.

In this study, we examined the effect of pharmaceutical excipients preferred in lipid-based formulations for lymphatic delivery on in vitro association of probucol with chylomicron (CM). CM stability study was performed under the conditions of room temperature, refrigeration and deep freezing to optimize the storage condition of CM dispersion prior to CM-binding study. The mean particle size, size distribution and zeta potential value were considerably maintained for 48 h under the refrigeration condition. CM-binding study was conducted using probucol incorporated in vehicles composed of solubilizer (Transcutol HP or ethanol or propylene glycol) or surfactant (Tween-80 or Tween-20 or Cremophor ELP), and CM dispersion obtained by a density-gradient ultracentrifugation. Levels of the association of probucol with CM were largely governed by solubility of probucol in pharmaceutical excipients tested in this study, and the ability of solubilizers tested to enhance the affinity of probucol with CM was much greater than that of surfactants tested. Furthermore, the association of probucol with CM was enhanced by increasing the amount of the drug solubilized in propylene glycol or Transcutol HP. Together, the result of this CM-binding study showed that solubilizers tested in this study can increase levels of the association of probucol with CM, potentially leading to an increase in lymphatic exposure of drugs. Thus, identifying pharmaceutical excipients having better solubilizing ability would be advantageous for enhanced lymphatic delivery.

Pectin Micro- and Nano-capsules of Retinyl Palmitate as Cosmeceutical Carriers for Stabilized Skin Transport.

Retinyl palmitate (RP)-loaded pectinate micro- and nano-particles (PMP and PNP) were designed for stabilization of RP that is widely used as an anti-wrinkle agent in anti-aging cosmeceuticals. PMP/PNP were prepared with an ionotropic gelation method, and anti-oxidative activity of the particles was measured with a DPPH assay. The stability of RP in the particles along with pectin gel and ethanolic solution was then evaluated. In vitro release and skin permeation studies were performed using Franz diffusion cells. Distribution of RP in each skin tissue (stratum corneum, epidermis, and dermis) was also determined. PMP and PNP could be prepared with mean particle size diameters of 593~843 µm (PMP) and 530 nm (i.e., 0.53 µm, PNP). Anti-oxidative activity of PNP was greater than PMP due largely to larger surface area available for PNP. The stability of RP in PMP and PNP was similar but much greater than RP in pectin bulk gels and ethanolic solution. PMP and PNP showed the abilities to constantly release RP and it could be permeated across the model artificial membrane and rat whole skin. RP was serially deposited throughout the skin layers. This study implies RP loaded PMP and PNP are expected to be advantageous for improved anti-wrinkle effects.

Combined Skin Moisturization of Liposomal Serine Incorporated in Hydrogels Prepared with Carbopol ETD 2020, Rhesperse RM 100 and Hyaluronic Acid.

We investigated the combined moisturizing effect of liposomal serine and a cosmeceutical base selected in this study. Serine is a major amino acid consisting of natural moisturizing factors and keratin, and the hydroxyl group of serine can actively interact with water molecules. Therefore, we hypothesized that serine efficiently delivered to the stratum corneum (SC) of the skin would enhance the moisturizing capability of the skin. We prepared four different cosmeceutical bases (hydrogel, oil-in-water (O/W) essence, O/W cream, and water-in-oil (W/O) cream); their moisturizing abilities were then assessed using a Corneometer®. The hydrogel was selected as the optimum base for skin moisturization based on the area under the moisture content change-time curves (AUMCC) values used as a parameter for the water hold capacity of the skin. Liposomal serine prepared by a reverse-phase evaporation method was then incorporated in the hydrogel. The liposomal serine-incorporated hydrogel (serine level=1%) showed an approximately 1.62~1.77 times greater moisturizing effect on the skin than those of hydrogel, hydrogel with serine (1%), and hydrogel with blank liposome. However, the AUMCC values were not dependent on the level of serine in liposomal serine-loaded hydrogels. Together, the delivery of serine to the SC of the skin is a promising strategy for moisturizing the skin. This study is expected to be an important step in developing highly effective moisturizing cosmeceutical products.

A vanadium tellurate, (NH(4))(2)[VO(2)](2)[TeO(4)(OH)(2)], containing two edge-shared square-pyramidal VO(5) groups.

A new ammonium vanadium tellurate, (NH(4))(2)[VO(2)](2)[TeO(4)(OH)(2)] (1), was hydrothermally synthesized and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy, and TG analysis. Compound 1 crystallizes in the monoclinic system, space group P2(1)/n: a = 8.9112(18) A, b = 15.151(3) A, c = 15.187(3) A, beta = 97.91(3)(o), V = 2030.9(7) A(3), Z = 8, R1 (I > 2sigma(I)) = 0.0295, wR2 (all data) = 0.0631. The structure of 1 consists of infinite anionic chains, {[VO(2)](2)[TeO(4)(OH)(2)]}(2-), of edge-sharing VO(5) square pyramids and TeO(4)(OH)(2) octahedra. Two VO(5) square pyramids are joined together by sharing their edge to form a V(2)O(8) binuclear unit. The V(2)O(8) and TeO(4)(OH)(2) units are alternatively connected to each other by sharing their edges to complete infinite zigzag anionic {[VO(2)](2)[TeO(4)(OH)(2)]}(2-) chains. The structure contains an extended network of O-H...O hydrogen bonds between the chains. The network of intermolecular hydrogen bonding results in layers parallel to the ab plane. Ammonium cations are hydrogen-bonded either to the oxygen atoms of the anionic chains or to each other in a complex arrangement.

Characteristics of Skin Deposition of Itraconazole Solubilized in Cream Formulation.

Itraconazole (ITZ) is an anti-fungal agent generally used to treat cutaneous mycoses. For efficient delivery of ITZ to the skin tissues, an oil-in-water (O/W) cream formulation was developed. The O/W cream base was designed based on the solubility measurement of ITZ in various excipients. A physical mixture of the O/W cream base and ITZ was also prepared as a control formulation to evaluate the effects of the solubilized state of ITZ in cream base on the in vitro skin deposition behavior of ITZ. Polarized light microscopy and differential scanning calorimetry demonstrated that ITZ was fully solubilized in the O/W cream formulation. The O/W cream formulation exhibited considerably enhanced deposition of ITZ in the stratum corneum, epidermis, and dermis compared with that of the physical mixture, largely owing to its high solubilization capacity for ITZ. Therefore, the O/W cream formulation of ITZ developed in this study is promising for the treatment of cutaneous mycoses caused by fungi such as dermatophytes and yeasts.

Moisturizing effect of serine-loaded solid lipid nanoparticles and polysaccharide-rich extract of root Phragmites communis incorporated in hydrogel bases.

This study evaluated the moisturizing effect of serine-loaded solid lipid nanoparticles (serine-SLN) and polysaccharide-rich reed (Phragmites communis) root extract (RRE) incorporated in hydrogel bases. The hydrogels with serine-SLN and/or RRE were carefully applied on the volar forearm of human volunteers. Their moisturizing efficacy was evaluated by monitoring conductance values using a skin surface hygrometer. The values of the area under the normalized conductance-time curve (AUCC) were developed and compared as a parameter for the water holding capacity of the skin. Hydrogels with serine-SLN did not significantly moisturize the skin, while hydrogel containing 0.25% RRE produced a significant increase in the moisture content of the skin. However, adding more than 0.25% of RRE into the hydrogel base decreased the moisturizing effect due to the marked reduction of viscosity. Significantly enhanced moisturizing effect was observed with the hydrogel containing 0.25% RRE and 3% serine-SLN, with AUCC increased 2.21 times compared to than blank hydrogel. The results imply that effective delivery of serine into the skin is possible using lipid-based nanocarriers and RRE, which could be a promising strategy to moisturize the skin effectively.

Preclinical Pharmacokinetic Evaluation of ß-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats.

ß-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of ß-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of ß-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of ß-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of ß-lapachone was 15.5%. The considerable degradation of ß-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of ß-lapachone may be resulted from the first-pass metabolic degradation of ß-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

Enhanced In Vitro Skin Deposition Properties of Retinyl Palmitate through Its Stabilization by Pectin.

The purpose of this study was to examine the effect of stabilization of retinyl palmitate (RP) on its skin permeation and distribution profiles. Skin permeation and distribution study were performed using Franz diffusion cells along with rat dorsal skin, and the effect of drug concentration and the addition of pectin on skin deposition profiles of RP was observed. The skin distribution of RP increased in a concentration dependent manner and the formulations containing 0.5 and 1 mg of pectin demonstrated significantly increased RP distributions in the epidermis. Furthermore, it was found that skin distribution of RP could be further improved by combined use of pectin and ascorbyl palmitate (AP), due largely to their anti-oxidative effect. These results clearly demonstrate that the skin deposition properties of RP can be improved by stabilizing RP with pectin. Therefore, it is strongly suggested that pectin could be used in the pharmaceutical and cosmetic formulations as an efficient stabilizing agent and as skin penetration modulator.