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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.

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.

The buccal mucosa has been investigated for the local drug therapy and the systemic delivery of potent peptides, proteins, and other small drug molecules that are subjected to hepatic metabolism and enzymatic degradation in the gastrointestinal tract. Being non-invasive, this route is more feasible for the delivery of therapeutic entities than that of invasive or parenteral drug administration. However, the mucosa of oral cavity represents a major barrier to drug penetration. In addition, the presence of several enzymes in saliva, salivary flow, discomfort feelings after administration of dosage forms, and bitter taste of the drugs have limited the drug delivery via the buccal cavity. Thus, extensive studies have been conducted to develop novel pharmaceutical formulations for effective buccal drug delivery. Various buccal dosage forms such as tablets, gels, and patches/films are now commercially available and have demonstrated high patient compliance. Recently, several manufacturing companies have launched new buccal drug delivery systems such as aerosol, sprays, and particulate systems and they have actively been investigated by numerous pharmaceutical scientists. If the successful development of such systems could be achieved, buccal drug delivery systems would be one of the most promising technology in the near future. In this review, we described the recent development of buccal dosage forms, anatomy of buccal mucosa, drug transport mechanisms, and formulation strategies to enhance the drug permeation through the buccal mucosa.

β-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 β-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 β-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 β-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of β-lapachone was 15.5%. The considerable degradation of β-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 β-lapachone may be resulted from the first-pass metabolic degradation of β-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

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.

Pharmaceutical excipients (PEs) are an essential part of drug products to make them have desirable characteristics. Most pharmaceutical excipients have been considered as biologically inert. However, recent studies showed that PEs affect pharmacokinetic behaviors of drugs in several manners when absorbed through gastrointestinal (GI) tract. For example, oral administration of the excipients such as nonionic surfactants could modulate cytochrome P450 enzymes, in GI tract and liver, and p-glycoprotein (p-gp) leading to changes in pharmacokinetic characteristics in vitro and in vivo. Sulfotransferase (SULT) is one of the phase II metabolism enzymes mainly found in the liver and small intestine and catalyzes the transfer of sulfuryl groups from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to hydroxyl or amino groups of the compounds. The biological functions of SULT include metabolism and detoxification of xenobiotics by sulfation. It can therefore be anticipated that inhibitors or enhancers of SULT alter the metabolic profiles of substrate drugs susceptive to the enzymes which may decrease or increase the bioavailability of the drug. For example, SULT1A1 and SULT1A3 play important roles in the pre-systemic inactivation of β2 agonists in the liver and intestine. Thus, inhibition of SULTs can lead to an increase in the bioavailability of β2 agonists. In this study, we attempted to investigate the possibility of the modulation of SULT by a wide range of PEs frequently used in the formulation of oral drug delivery systems to improve the bioavailability of drugs that are extensively degraded by SULTs.

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.

− Pharmaceutical technology has primarily focused on the development of the best dosage forms dependingon the route of administration. The design of dosage forms is greatly influenced by the route of administration. Due to avariety of advantages such as avoidance of first-pass effect, abundant blood supply and easy access to the absorption site,the oral cavity has frequently been selected as a site for drug delivery. Since the oral cavity is relatively unique from theanatomical and physiological viewpoint, one should always consider these conditions when designing the drug delivery sys-tems for the oral cavity. In this regard, the current review paper was prepared to summarize the essential features of the drugdelivery systems utilized in the oral cavity, along with the introduction of various dosage forms developed to date.Key words − Oral cavity, Buccal, Bioadhesive, Mucoadhesive, Drug delivery system, Dosage forms A number of buccal delivery systems are being investigatedand have been used for drug absorption via the oral mucosa.These include aqueous solutions (e.g. mouth wash, a dose ≤25 mL), conventional buccal and sublingual tablets, liquid-filled capsules, adhesive tablets, adhesive gels, adhesivepatches, chewing gums, metered-dose aerosols and devicesattached to the teeth or implanted in the tooth enamel (Merkleet al., 1990). The selection of dosage form primarily relies onthe therapeutic intention, such as rapid or prolonged effect andsystemic or local therapeutic effect, as well as the physico-chemical properties of the drug molecules. It would be addi-tionally important to increase the patient acceptability of thedelivery system i.e. ease of use and avoidance of discomfort.Karsenty et al. (1994) have evaluated clinically the patientacceptance of a transmucosal patch (a matrix of polyacrylicacid and polyisobutylene with adhesive impermeable backinglayer) with regard to comfort, irritation and feeling when pre-sented and removed. They reported that it is important to dem-onstrate patient acceptance if the delivery system is to gain awide range of applicability for a number of therapies. It is alsoimportant that the additives used to formulate oral mucosaldosage forms do not stimulate salivary secretion as this maycause the loss of a large fraction of the active ingredient priorto absorption. Rathbone et al. (1994) have reported that thesize, shape and the thickness of the delivery system should beconsidered to maximise patient compliance. Anders andMerkle (1989) have proposed the appropriate dimensions ofdosage forms for buccal use. For an inflexible conventionaltablet, 5-8 mm in diameter is suitable for comfort and the abil-ity of the patient to constantly detect its presence. In the caseof a flexible patch, the maximum size would be 10-15 cm

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 (I2sigma(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.

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.

A new ammonium vanadium tellurate, (NH4)2[VO2]2[TeO4(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 P21/n: a = 8.9112(18) A, b = 15.151(3) A, c = 15.187(3) A, β = 97.91(3)o, V = 2030.9(7) A3, Z = 8, R1 (I > 2σ(I)) = 0.0295, wR2 (all data) = 0.0631. The structure of 1 consists of infinite anionic chains, {[VO2]2[TeO4(OH)2]}2−, of edge-sharing VO5 square pyramids and TeO4(OH)2 octahedra. Two VO5 square pyramids are joined together by sharing their edge to form a V2O8 binuclear unit. The V2O8 and TeO4(OH)2 units are alternatively connected to each other by sharing their edges to complete infinite zigzag anionic {[VO2]2[TeO4(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 hydroge...

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.