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The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus (HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated self-microemulsifying drug delivery system (S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS. Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper self-microemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS. Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system., Graphical abstract Supersaturated self-microemulsifying drug delivery systems designed in this study were demonstrated to enhance the intestinal lymphatic absorption of saquinavir in vivo through inhibiting the drug precipitation in gastrointestinal fluid. Image, graphical abstract

Liposomes have demonstrated great potentials as protein carriers in various pharmaceutical applications. However, low loading amount of proteins in liposomes have been a major challenge for maximizing the therapeutics potential of the proteins. We thus aimed to enhance the loading amount of a model protein, lysozyme, in liposomes by controlling key experimental variables of a reverse phase evaporation method. The loading amount of lysozyme in liposomes was evaluated with changing type of organic solvents used, weight ratio of lysozyme/phosphatidylcholine, and volume ratio of aqueous to organic phase along with particle characterization before and after freeze-drying procedure. As a result, the loading amount of lysozyme in liposomes was considerably enhanced and the physical stability of the liposomes was maintained without any significant changes in the particle characteristics for 7 days. The findings of this study would be useful for highly efficient loading of protein therapeutics in liposomes, leading to improved therapeutic effects of the drugs.

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

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.

This study aimed at the evaluation of plasma level profiles of choline produced after the oral administration of choline alphoscerate (CA). For this purpose, a high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) analytical method was developed and validated. Baseline correction technique was employed to monitor the CA-related choline in plasma by subtracting background levels of choline from total choline levels measured after the drug administration. Choline was well separated in the plasma matrix under the analytical conditions employed for HPLC/MS/MS and the analytical method developed for the monitoring of choline in plasma was well validated. The endogenous choline levels in plasma under fasting condition were measured to be 7.78 ± 1.74 µmol/L for test period 1 and 7.88 ± 1.78 µmol/L for test period 2, respectively, and were considerably increased after consumption of meals. The corrected choline levels in plasma produced only by the oral administration of CA could be evaluated by subtracting the background levels of choline monitored before the drug was administered. The pharmacokinetic parameters estimated for test and control formulations were quite similar based on the comparison of C max, AUC12h , and T max, indicating that these are biologically equivalent dosage forms. The results of our study consequently suggest that the baseline correction method in evaluating plasma concentration profiles of endogenous substances is useful.

Celecoxib is a non-steroidal, anti-inflammatory drug used in the treatment of pain and inflammation associated with rheumatoid arthritis, and several other inflammatory disorders. It is a class II compound according to the Biopharmaceutics Classification System owing to its low water solubility and high membrane permeability. The objective of this study was to improve the solubility and dissolution rate of celecoxib using solid surfactant technology that might be useful in developing solid dosage forms. Solid surfactant was developed by mixing and grinding together a liquid surfactant (Tween 80) with various inorganic carriers like Fujicalin® (Dibasic Calcium Phosphate Anhydrous), Pineflow® (Porous-structured Maltodextrin), Neusilin® (Magnesium Alumino metasilicate) and Aerosil® (Colloidal Silicon dioxide) in a mortar and pestle in different ratios of liquid surfactant and the carrier to obtain solid surfactants. The celecoxib tablets prepared with solid surfactants were then evaluated for their solubility and dissolution properties. Among the fillers used, Fujicalin showed the highest solubilization capacity for celecoxib. The dissolution behaviors of various tablets prepared with solidified surfactants were compared to those of conventional celecoxib tablets in a simulated gastric fluid. Celecoxib tablets prepared using solidified surfactants showed improved dissolution behaviors when compared to the conventional counterparts. Fujicalin solidified Tween 80 was further analyzed by powder X-ray diffraction analysis, differential scanning calorimetry thermographs and reverse phase high performance liquid chromatography.

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.

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.

The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.

The aim of this study was to develop liposomal doxorubicin-loaded chitosan microspheres (LDox-CSMS) for anti-cancer chemoembolization. LDox-CSMS and doxorubicin-loaded CSMS (Dox-CSMS) devoid of liposomal carrier were prepared with an emulsification and cross-linking method. Various stirring rates were required to obtain large fractions of CSMS in the size range of 300–500 μm. Drug loading amounts were considerably influenced by the amount of doxorubicin-loaded liposomes added. Drug release from LDox-CSMS was controlled by the drug loading amount, which was varied by the addition of liposomal doxorubicin. These results indicate that LDox-CSMS can be used as an advanced chemoembolic agent that can control drug release behaviors.

Sustained release (SR) tablets containing solid dispersions (SD) granules of a poorly water-soluble drug were prepared to investigate the controlled pH-independent release of the drug. Losartan potassium (LST), an anti-hypertensive agent was chosen as a model drug because of its pH-dependent solubility and short elimination half-life. Poloxamer 188 was used as an SD carrier. A free-flowing SD granule was prepared by adsorbing the melt of the drug and poloxamer 188 onto the surface of an adsorbent, Aerosil 300 (fumed silicon dioxide), followed by direct compression with polyethylene oxide (PEO, 5 × 10(6)) to obtain an SD-loaded SR (SD-SR) matrix tablet. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) revealed partially amorphous structures of the drug in the SD granules. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) images indicated adsorption of SD granules onto the surface of the adsorbent. The SD granules dissolved completely within 10 min, a dissolution rate much higher than that of pure LST. Moreover, pH-independent sustained release of LST from the SD-SR tablet was achieved for 2h in gastric fluid (pH 1.2) and for 10h in intestinal fluid (pH 6.8). A combination of SD techniques using surface adsorption and SR concepts is a promising approach to control the release rate of poorly water-soluble drugs in a pH-independent manner.

Nuclear magnetic resonance (NMR) techniques coupled with multivariate data analysis were used to conduct monitoring of biochemical changes of black raspberry fruits at different stages of maturation and under various extraction and NMR dissolution solvent conditions: extraction with 50% methanol and D 2 O as an NMR dissolution solvent, extraction with 50% methanol and 50% methanol- d 4 as an NMR dissolution solvent, and extraction with 100% ethyl acetate and 100% methanol- d 4 as an NMR dissolution solvent. Partial least-squares discriminant analysis reliably distinguished black raspberry fruits according to the maturation stage, whereby the relative levels of various compounds such as amino acids, organic acids, sugars and phenolic compounds were compared using analysis of variance. Sucrose and most of the amino acids, and organic acids decreased, whereas fructose, glucose, and cyanidins increased in relative concentration according to maturation of black raspberry fruits. The total number and kinds of assigned compounds of the three solvent systems were also compared. This research demonstrates that the metabolic profile of black raspberry fruits changes during maturation, and provides objective criteria for determining the stage of black raspberry fruit maturation via a 1 H NMR-based metabolomics technique using multiple solvent systems.

Drug release from a solid form of self-emulsifying drug delivery system (SEDDS) has greatly been limited due to strong adsorption and physical interaction with carriers. To facilitate drug release process in the stomach, an acid-soluble powderizing carrier, Fujicalin(®) was evaluated together with different disintegrants and hydrophilic lubricants.Immediate-release self-emulsifying tablets (IR-SETs) of ibuprofen (IBU) was prepared with solidified SEDDS of IBU, various disintegrants, and lubricants, and drug release was evaluated to develop IR-SET that can release IBU with a similar IBU release rate to that obtained with liquid SEDDS.The liquid SEDDS consisted of Capryol 90, Cremophor EL, Labrasol, and IBU at a ratio of 3:4:3:3, and was solidified with various adsorbents. The powderized SEDDS was tabletted by a direct compression. Fujicalin(®)-based SEDDS tablets demonstrated remarkably higher dissolution rate of IBU compared with Neusilin(®) and Neosyl(®)-based SEDDS tablets. The IR-SET formula of IBU prepared with Fujicalin(®) as an adsorbent, Polyplasdone(®) as a disintegrant, and sodium bicarbonate as a co-disintegrant showed over 90% of initially loaded dose of IBU released within 5 min in a stimulated gastric juice (pH 1.2), exhibiting almost equivalent rate of IBU release to that shown by liquid SEDDS. The particle size analysis revealed no significant differences in droplet sizes of the microemulsions formed from liquid (116 nm) and IR-SET (110 nm).The novel IR-SET can be promising as a fast-releasing SEDDS tablet of IBU for fast onset of action.

This article investigates the impact of elastic liposomes on enhancing the skin delivery of genistein and the influences of skin tissues with or without hair follicles on permeation and accumulation properties of genistein from liposomal suspensions. The greater permeation rate and deposition values of genistein were observed from the elastic liposomes than conventional liposomes in haired skin. When measured with hairless skin, the flux and skin deposition values of genistein in elastic liposomes were significantly decreased compared to conventional liposomes, indicating that the percutaneous delivery of elastic liposomes was considerably influenced by existence of hair follicles in the skin tissue.

1H NMR-based metabolomics technique. Partial least squares discriminant analysis (PLS-DA) was used as the multivariate statistical analysis of the 1 H NMR data sets. There was a clear separation between various Glycyrrhiza species in the PLS-DA derived score plots. The PLS-DA model was validated, and the key metabolites contributing to the separation in the score plots of various Glycyrrhiza species were lactic acid, alanine, arginine, proline, malic acid, asparagine, choline, glycine, glucose, sucrose, 4-hydroxyphenylacetic acid, and formic acid. The compounds present at relatively high levels were glucose, and 4-hydroxyphenylacetic acid in G. glabra; lactic acid, alanine, and proline in G. inflata; and arginine, malic acid, and sucrose in G. uralensis. This is the first study to perform the global metabolomic profiling and differentiation of Glycyrrhiza species using 1 H NMR and multivariate statistical analysis.

In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol, but the reduced release profile for PxLN-C. PxLN or Taxol was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUC of PxLN-H was 3.4-fold greater than that of Taxol. PxLN-H gave higher biodistribution in all tissues than did Taxol. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.

The bark of Alnus japonica has been used for the treatment of fever, hemorrhage and diarrehea in oriental traditional medicine. Recently, it was revealed that the diarylheptanoids from the bark of Alnus japonica possess anti-inflammatory activity and are expected to be applicable for atopic dermatitis. In this study, oregonin, one of major active components in the bark of Alnus japonica, was developed in the form of semisolid formulations for topical delivery. Oregonin was incorporated into four ointment bases: O/W cream, W/O cream, hydrophilic ointment and lipophilic ointment. Oregonin release from all formulation prepared was evaluated. Franz cell method and immersion method were employed to characterize the release patterns of drug from each formulation based on solvent availability. O/W cream showed a better release profile than the other formulations when evaluated with Franz cell method with an order of O/W cream, hydrophilic ointment, W/O cream and lipophilic ointment. In the immersion method, hydrophilic ointment showed the greatest release rate at times 1 hour exceeding compared to other bases with an order of hydrophilic ointment, O/W cream, W/O cream and lipophilic ointment. Hydrophilicity and solvent availability of formulation seems to significantly influence the release rate of oregonin from ointment bases. In this study, we successfully characterized the oregon in ointment and found that o/w cream is a promising formulation for the topical delivery of oregonin.

To develop topical nitroglycerin (NTG) preparation far chronic anal fissure treatment, the release rate of NTG should be controlled carefully. For this, microemulsion was prepared from the phase diagram construction with Cremophor ELP, ethanol and Labrafil and the topical gel was prepared by dispersing NTG containing microemulsion into hydrophilic polymers. in viかo release characteristics were evaluated with Franz diffusion cell using cellulose membrane and compared with control hydrogels. The release rate of NTG was followed order kinetics and, when comparing the NTG release from control hydrogel with that from the microemulsion-based hydrogel, the NTG release rate was controlled by the content of polymers within continuous phase and the concentration of dispersed phase.

To prepare freeze-dried ascorbyl palmitate (AsP)-containing liposome which can protect the drug from moisture attack and be used instantly by mixing with water for anti-aging and skin whitening therapy, AsP was encapsulated into liposomes and freeze-dried with trehalose. The freeze-dried liposome formulations were characterized by measuring water contents, particle size, time required for complete reconstitution. With the freeze-dried liposomes, we performed the stability test under accelerated conditions, skin permeation and localization test. The measurement of the time to perfect reconstitution showed that the freeze-dried liposomes can be changed to their initial state rapidly and short term stability test of AsP in reconstituted liposomes under accelerated conditions confirmed that the stability of AsP was considerably enhanced as compared to freshly prepared liposomes. The skin permeation and localization properties of AsP in reconstituted liposomes were not significantly different, indicating that the liposomal structures were maintained before and after freeze-drying. In conclusion, the freeze-drying method provided a possible way to overcome the instability issue of AsP induced by the moisture and reproduced similar skin permeation and localization properties as shown by freshly prepared liposomes.

To enhance skin permeation of ascorbyl palmitate (AsP), it was encapsulated in liposomes, and formulated into liposomal hydrogel (lipogel) by dispersing the liposome into poloxamer hydrogel matrix. To improve the skin permeation of AsP, we applied electric current supplying system that mimics an electric skin massager. We evaluated the effects of composition and surface charge of the liposomes and electrical assistance on the skin permeation of AsP. In the passive transport study, the permeated amounts of AsP from all the lipogels tested were higher than that of control hydrogel which contains Transcutol used to solubilize AsP. In the cathodal delivery condition with a fixed cathodal current of 0.4 mA/cm2, the skin permeation characteristics of the negative lipogels were superior to that obtained with the neutral lipogels and the drug permeation was more increased with increased surface negative charge of the liposomes. In conclusion, the lipogel system was thought as a helpful drug delivery system to enhance skin permeation of AsP. Combined use of negative lipogel with cathodal electric assistance was found to be promising in enhancing the skin delivery of AsP.

The purpose of this investigation was to characterize the in vitro stability and in vivo disposition of paclitaxel in rats after solubilization of paclitaxel into hydrotropic polymeric micelles. The amphiphilic block copolymers consisted of a micellar shell-forming poly(ethylene glycol) (PEG) block and a core-forming poly(2-(4-vinylbenzyloxy)-N,N-diethylnicotinamide) (P(VBODENA)) block. N,N-Diethylnicotinamide (DENA) in the micellar inner core resulted in effective paclitaxel solubilization and stabilization. Solubilization of paclitaxel using polymeric micelles of poly(ethylene glycol)-b-P(D,L-lactide) (PEG-b-PLA) served as a control for the stability study. Up to 37.4 wt % paclitaxel could be loaded in PEG-b-P(VBODENA) micelles, whereas the maximum loading amount for PEG-b-PLA micelles was 27.6 wt %. Thermal analysis showed that paclitaxel in the polymeric micelles existed in the molecularly dispersed amorphous state even at loadings over 30 wt %. Paclitaxel-loaded hydrotropic polymeric micelles retained their stability in water for weeks, whereas paclitaxel-loaded PEG-b-PLA micelles precipitated in a few days. Hydrotropic polymer micelles were more effective than PEG-PLA micelle formulations in inhibiting the proliferation of human cancer cells. Paclitaxel in hydrotropic polymer micelles was administered orally (3.8 mg/kg), intravenously (2.5 mg/kg), or via the portal vein (2.5 mg/kg) to rats. The oral bioavailability was 12.4% of the intravenous administration. Our data suggest that polymeric micelles with a hydrotropic structure are superior as a carrier of paclitaxel due to a high solubilizing capacity combined with long-term stability, which has not been accomplished by other existing polymeric micelle systems.

Poloxamer-based hydrogel formulation for the topical delivery of ascorbic acid(AsA) was prepared and the effect of limonene on AsA skin permeation and localization was evaluated. In vitro rat skin permeation study, the AsA skin permeation of limonene-containing hydrogel was about 3 to 5 fold higher than control hydrogel. However the amount of permeated AsA was independent to the concentration of limonene. On the other hand the localized amount of AsA after 2 h increased proportion to the content of limonene. The increase in the ratio of localized AsA() to permeated AsA() was attributed to the limonene's ability of making polar pathway within stratum corneum by interacting on lipid domain of the skin and the AsA's hydration effect on the stratum corneum and effect on the protein domain of the skin.

A highly sensitive high-performance liquid chromatographic-tandem mass spectrometric method (HPLC-MSMS) has been developed to quantify itraconazole in human plasma for the purpose of pharmacokinetic studies. Sample preparation was carried out by liquid-liquid extraction using loratadine as an internal standard. Chromatographic separation used a YMC column, giving an extremely fast total run time of 3 min. The method was validated and used for the bioequivalence study of itraconazole tablets in healthy male volunteers (n = 31). The lower limit of detection proved to be 0.2 ng /mL for itraconazole.

A highly sensitive high-performance liquid chromatographic quantification method with fluorescence detection was developed and validated for the determination of doxazosin in human plasma. The developed method employed one-step extraction of doxazosin from plasma matrix with ethyl acetate using propranolol as an internal standard. Chromatographic separation was obtained within 8.0 min using a reverse-phase Capcell-Pak C18 column (150 × 4.6 mm i.d., 5 µm) and the mobile phase consisted of methanol–water containing 10 mM perchloric acid and 1.8 mM sodium heptane sulfonic acid (50:50, v/v) and was set at a flow rate of 1.5 mL/min. The calibration curve constructed was linear in the range of 0.3–50.0 ng/mL. The proposed method achieved a lower limit of quantification of 0.3 ng/mL, better than the reported HPLC methods. Average recoveries of doxazosin and the internal standard from human plasma matrix were 87.0 and 85.9%, respectively. The present method was validated by evaluating the precision and accuracy for inter- and intraday variation in the concentration range 0.3–50 ng/mL. The precision values expressed as relative standard deviations in the inter- and intraday validation were 1.17–6.29 and 0.84–5.94%, respectively. This method was successfully applied to the bioequivalence study of two doxazosin controlled release tablets in healthy, male human subjects. Copyright © 2006 John Wiley & Sons, Ltd.

The objectives of the current work is to understand the factors impacting the formulation and performance of a Carbopol mucoadhesive buccal delvery system for a model peptide drug, enkephalin (DADLE, Mw=569.7) with comparable chemical and enzymatic stability. Specifically, in vitro buccal DADLE delivery from the cross-linked poly(acrylic acid) (PAA) hydrogel system was characterized. In addition, the influences of several penetration enhancers on the ex vivo buccal absorption of DADLE were also studied. In this study, the PAA hydrogels generally swell to 100% of their original weight in the phosphate pH 7.4 buffer. The water penetration into the PAA hydrogel occurred based on a zero-order kinetics for the first 60 min and steadily decreased afterwards. From the release study, it can be seen that the initial DADLE release was so rapid and the rate of release of DADLE decreased as the time elapsed. The porcine buccal tissue was found to be permeable to DADLE with a flux value of . From the ex vivo diffusion study, it was found that sodium taurodihydrofusidate showed a greater degree of enhancement compared to the phospholipids with an Enhancement Ratio (ER) of 8.7 compared to 2.7 and 1.9 for didecanoylphosphatidylcholine and lysophosphatidylcholine, respectively. The work encompassed within this paper has demonstrated the feasibility of using the PAA hydrogel delivery system with its good mucoadhesive properties for the buccal delivery of peptides.

Recently increasing attention has been focused on solid lipid nanoparticles (SLN) as a parenteral drug carrier due to its numerous advantages that can come from both polymeric particle and fat emulsions, together with the possibility of controlled release and increasing drug stability. Lipophilic drugs such as paclitaxel, cyclosporin A, and all-trans retinoic acid have been successfully entrapped in SLN but the incorporation of hydrophilic drugs in SLN is very limited because of their very low affinity to the lipid. Therefore, as a new approach to improve the loading of hydrophilic drugs, a w/o/w emulsion technique has been developed. The primary objective of the current study was to improve the loading efficiency of a model hydrophilic drug, glycine (Log P = -3.44) into SLN. The proposed preparation process is as follows: A heated aqueous phase consisting of 0.1 ml of glycine solution in water (100 mg/ml), and poloxamer 188 (5 mg) were then added to a molten oil phase containing precirol (100 mg) and lecithin (5 mg). This mixture was dispersed by sonicator, leading to a w/o emulsion. A double emulsion (w/o/w) was formed after the addition of 2% poloxamer solution to the above dispersed system. After cooling the double emulsion, solid lipid nanosuspensions were successfully formed. The lipid nanoparticles had the mean particle size of 441.25 nm, and the average zeta potential of -20.98 mV. The drug loading efficiency was measured to be 8.54% and the drug loading amount was measured to be 0.92%. The w/o/w emulsion method showed an increased loading efficiency compared to conventional o/w emulsion method.

Tamsulosin has been frequently used for the treatment of benign prostatic hyperplasia. To avoid dose-dependent side effects of tamsulosin upon oral administration, the development of sustained-release delivery system is required, that can maintain therapeutic drug levels for a longer period of time. The aim of this study was therefore to formulate sustained-release tamsulosin matrix tablets and assess their formulation variables. We designed enteric coated sustained-release tamsulosin matrices to fulfill above statement. Aqueous microchannels in the enteric film need to be formed in order to obtain tamsulosin release even in an acidic environment such as gastric region. In the sustained-release tamsulosin matrix, low viscosity hydroxypropylmethylcellulose was used as a rate controller. Povidone K30 was also added to the matrices to facilitate water uptake so that a decrease in the release rate of tamsulosin as time elapses was prevented, possibly leading to pseudo zero-order release of the drug. The matrices were enteric-coated with hydroxypropylmethylcellulose phthalate (HPMCP), along with povidone K30 as an aqueous microchannel former. With the aqueous microchannels formed within the enteric film, tamsulosin could be released in an acidic condition. The release of tamsulosin decreased with increasing thickness of HPMCP membrane while the release rates of tamsulosin from those having different HPMCP thickness in pH 7.2 aqueous media were not considerably different, indicating that the enteric film was promptly dissolved at pH 7.2. These results clearly suggest that the sustained-release oral delivery system for tamsulosin could be designed with satisfying drug release profile approved by the KFDA.

New formulations of amlodipine maleate tablet have been investigated to enhance the stability of the drug against light and humidity. Three kinds of amlodipine maleate tablets were prepared. One is prepared by previously known formulation (formulation C), the others were by new formulations using hydrophilic polymer coated granules (formulations A and B). Amlodipine maleate powder was coated with to produce the coated granules and it was mixed with other excipients to produce the tabletting mass of new formulations A and B. Dissolution rate of newly formulated tablets was over 80% within 10 minutes in 0.01 M HCl medium, and its dissolution pattern was similar to that of tablet. After 6 months storage under accelerated conditions, residual drug contents of tested formulations (A and B) were not significantly different from formulation C, ranging from 96.2 to 100.4%. Meanwhile, dissolution amount of formulation C was significantly reduced compared to that of formulation A (p

The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers, year in age and kg in body weight, were divided into two groups and a randomized cross-over study was performed. After oral administration of a tablet containing 800 mg of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed and untransformed . The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for , and , respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., and for , and , respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters, , and met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.

The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using an ex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

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.

The possible role of water inthe mucoadhesion phenomenon exhibitedby the liquid crystalline phases of glyceryl monooleate was investigated using an in-vitro tensile strength technique. The mucoadhesion of the liquid crystalline phases of glyceryl monooleate was found to occur following uptake of water. The mucoadhesive force of the cubic phase was consistent since it is not capable of taking up additional water. An increase in pre-load period greatly facilitated the mucoadhesion of glyceryl monooleate (0% w/w initial water content), suggesting that the mucoadhesion is dependent upon the extent of the dehydration of the substrate. A good linear relationship between initial water content of the liquid crystalline phases and mucoadhesive force led to the conclusion that the mucoadhesive force increased with decreasing initial water concentration. Rheological properties of the liquid crystalline phases were also studied to allow a correlation between physical changes and mucoadhesion of the liquid crystalline phases, revealing that higher water concentrations in the liquid crystalline phases led to a more ordered structure that showed less mucoadhesion. The results of this study indicated that the mucoadhesive force ofthe liquid crystalline phases of glyceryl monooleate is determined by the capability to take up water from a water-rich environment. It may, therefore, be advantageous to use the lamellar phase as a buccal drug carrier as opposed to the relatively less mucoadhesive cubic phase.

Swelling and [D-Ala(2), D-Leu(5)]enkephalin (DADLE) release from the lamellar and cubic liquid crystalline phases of glyceryl monooleate (GMO) were studied using two in vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and glyceryl monooleate (0% w/w water content) and DADLE release from the liquid crystalline phases were temperature dependent. The swelling ratio was greater at 20 degrees C than 37 degrees C while DADLE release increased at 37 degrees C compared to 20 degrees C for both the lamellar and cubic phases. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. However, DADLE release increased with increasing initial water content, which corresponded to increased viscosity. The swelling and DADLE release profiles obtained using a Franz cell method with a moist nylon membrane to mimic buccal drug release conditions were slower than the total immersion method. These results show that the swelling and DADLE release strongly depended on temperature, the initial water content of the liquid crystalline matrix and the methodology employed for determining the swelling and DADLE release.

The purpose of this study is to investigate the recoverability of freeze-dried chitosan microspheres (MS). The factors influencing the integrity of chitosan MS during freeze-drying and rehydration procedures were determined, with focusing on choosing a suitable rehydration method and a freeze-drying excipient. Mean MS size, size distribution and sphericity of recovered chitosan MS were evaluated. Furthermore, the impacts of freeze-drying and rehydration procedure on the elasticity of chitosan MS were explored and the release profiles were evaluated. The recoverability of lyophilized chitosan MS was largely dependent on rehydration method and freeze-drying excipients. When using the optimized recovery processes, deformable drug-loaded chitosan MS can be rapidly recovered to exhibit the initial physico-mechanical properties such as elasticity. Release profiles also were not significantly changed after rehydration procedure. It is therefore expected drug-loaded chitosan MS can be stably freeze-dried with the prevention of drug release during storage and rapidly recovered to be used as deformable embolic materials possibly applicable for anti-cancer embolotherapy.

In order to enhance the dissolution profile and oral bioavailability of megestrol acetate (MA), solid dispersions of MA (MASDs) were formulated with copovidone and crystal sugar as a hydrophilic polymeric carrier and an inert core bead, respectively. Solvent evaporation method and fluidized bed coating technique were employed. MASDs were categorized as crystalline solid dispersion by the characterization of differential scanning calorimetry and X-ray diffraction. The mass-median diameters of MASDs were in a range of 1.4 to 2.6 μm. Based on drug to polymer ratio, MASD (1:1) and (1:2) were considered as optimized formulations, resulting in a smooth-surfaced homogeneously coated layer with enhanced dissolution rate. Dissolution of MASD was gradually increased up to 15 min, after which it reached a plateau. For the initial period, dissolution rates were in the decreasing order of MASD (1:2) ≥ MASD (1:1) > MASD (1:3) > MASD (1:5) > MASD (1:0.5) > MA powder. In the comparative pharmacokinetic study with Megace OS, a reference drug product, MASD (1:1) showed improved bioavailability of over 220% with 2-fold higher Cmax and 30% faster Tmax. We conclude that MASD (1:1) is a good candidate for the development of oral solid dosage forms.

The goal of our investigation was to develop oral solution of coenzyme Q10 (CoQ10) by using self-emulsifying systems. CoQ10 is practically insoluble in water. Therefore, it is difficult to develop oral solution of CoQ10. To solubilize CoQ10 and to develop it as oral solution, self-emulsifying systems consisted of oil, surfactant and co-surfactant were studied and using the self-emulsifying system chosen, oral solution was developed. After the evaluation of solubilizing abilities of various oils and surfactants, the self-emulsifying system consisted of acetylated monoglyceride (AM) as oil, polyoxyethylene (20) sorbitan monolaurate (P2SM) as surfactant and propylene glycol laurate (PGL) as co-surfactant, was chosen because the emulsions prepared by that system showed spontaneous emulsification and transparent appearance. All of these components could be used for the development of functional foods. Finally, a CoQ10 solution with concentrations of 100 mg/70 ml and 100 mg/100 ml could successfully be developed by the addition of water to one milliliter of self-emulsifying system consisted of AM (10%), P2SM (70%) and PGL (20%) along with 100 mg of CoQ10. This oral solution formulation was stable for more than one month.

Olmesartan medoxomil (OLM) is an antihypertensive angiotensin II receptor blocker. OLM has a low bioavailability (BA), approximately 26% in humans, due to its low water solubility and efflux by drug resistance pumps in the gastrointestinal tract. Self-microemulsifying drug delivery system (SMEDDS), which is easily emulsified in aqueous media under gentle agitation and digestive motility, was formulated to increase the oral BA of OLM. Among the surfactants and oils studied, Capryol 90, Tween 20, and Tetraglycol were chosen and combined at a volume ratio of 1:6:3 on the basis of equilibrium solubility and phase diagram experiments. The mean droplet size of SMEDDS was 15 nm. In an oral absorption study in rats, SMEDDS formulation brought faster absorption compared to suspension, showing a T(max) value of 0.2 hr. The C(max) and AUC values of SMEDDS formulation were significantly higher than those of suspension, revealing a relative BA of about 170%. Our study demonstrated the potential usefulness of SMEDDS for the oral delivery of poorly absorbable compounds, including OLM.

As an initial step to develop the transdermal delivery system of glucosamine hydrochloride (GL-HCl), the permeation study across the rat skin in vitro was performed to identify the most efficient vehicle with regard to the ability to deliver GL-HCl transdermally. The GL-HCl formulations such as o/w cream, liposome suspension, liposomal gel, and liquid crystalline vehicles were prepared and compared for transdermal flux of GL-HCl. The liquid crystalline vehicles were more effective in increasing the skin permeation of GL-HCl than o/w cream and liposomal vehicles. Of the liquid crystalline vehicles tested, the permeation enhancing ability of the cubic phase was greater than that of the hexagonal phase when the nanoparticle dispersion was used. The skin permeation enhancing ability of the cubic nanoparticles for GL-HCl was further increased by employing both oleic acid and polyethylene glycol 200. Therefore, the cubic liquid crystalline nanodispersion containing oleic acid and PEG 200 can provide a possibility of clinical application of transdermal GL-HCl.

The purpose of the present study was to determine whether Pluronic F127 polymeric micelles could improve the oral bioavailability of a poor water-soluble drug, such as genistein. Genistein is a phytoestrogen that has estrogenic activity. F127 triblock copolymer consists of PEO100-PPO65-PEO100. Genistein was incorporated in the Pluronic F127 polymeric micelles by a solid dispersion method. The genistein release of genistein-loaded polymeric micelles was studied in vitro (in pH 1.2 and pH 6.8). And the oral bioavailabilities of genistein powder and genistein-loaded micelles were estimated at a dose of 4.0 mg/kg as genistein in rats. Drug loading amount and drug loading efficiency were 11.18% and 97.41%, respectively. The average size of the genistein-loaded polymeric micelles was 27.76 nm. And genistein release of the genistein-loaded polymeric micelles in vitro was 58% (pH 1.2) and 82% (pH 6.8). The bioavailability of genistein-loaded polymeric micelles was better than genistein powder. Consequently, Pluronic F127 polymeric micelles are an effective delivery system for the oral administration of genistein.

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.

An O/W microemulsion system was developed to enhance the skin permeability of aceclofenac. Of the oils studied, Labrafil® M 1944 CS was chosen as the oil phase of the microemulson, as it showed a good solubilizing capacity. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, Cremophor® ELP, and co-surfactant, ethanol, for micoemulsion formation. Eight different formulations with various values of oil of 6–30%, water of 0–80%, and the mixture of surfactant and co-surfactant (at the ratio of 2) of 14–70%. Thein vitro transdermal permeability of aceclofenac from the microemulsions was evaluated using Franz diffusion cells mounted with rat skin. The level of aceclofenac permeated was analyzed by HPLC and the droplet size of the microemulsions was characterized using a Zetasizer Nano-ZS. Terpenes were added to the microemulsions at a level of 5%, and their effects on the skin permeation of aceclofenac were investigated. The mean diameters of the microemulsions ranged between approximately 10≈100 nm, and the skin permeability of the aceclofenac incorporated into the microemulsion systems was 5-fold higher than that of the ethanol vehicle. Of the various terpenes added, limonene had the best enhancing ability. These results indicate that the microemulsion system studied is a promising tool for the percutaneous delivery of aceclofenac.

Research in this paper focuses on the kinetic evaluation of swelling of the liquid crystalline phases of glyceryl monooleate (GMO). Swelling of the lamellar and cubic liquid crystalline phases of GMO was studied using two in vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and GMO having 0 %w/w initial water content was temperature dependent. The swelling ratio was greater at 20 degrees C than 37 degrees C. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. The swelling rates obtained using the Franz cell method with a moist nylon membrane to mimic buccal drug delivery situation were slower than the total immersion method. The swelling was studied by employing first-order and second-order swelling kinetics. The swelling of the liquid crystalline phases of GMO could be described by second-order swelling kinetics. The initial stage of the swelling (t4 h) followed the square root of time relationship, indicating that this model is also suitable for describing the water uptake by the liquid crystalline matrices. These results obtained from the current study demonstrate that the swelling strongly depends on temperature, the initial water content of the liquid crystalline phases and the methodology employed for measuring the swelling of GMO.

Simultaneous evaluation of the permeation and washout of a peptide from the mucoadhesive liquid crystalline phases of glyceryl monooleate (GMO) has been investigated using a donor compartment flow-through diffusion cell. [D-Ala2, D-Leu5]enkephalin (DADLE) was incorporated into the cubic and lamellar liquid crystalline phases of GMO and applied to excised porcine buccal mucosa mounted in the donor compartment flow-through cell. Phosphate-buffered saline pH 7.4 (PBS) was pumped across the upper surface of the liquid crystalline phases to mimic salivary flow. The steady-state fluxes of DADLE and GMO from the cubic phase were significantly greater than that from the lamellar phase (P0.01). There was no statistical difference between the amounts of DADLE and GMO washed out from the lamellar and cubic phases (P0.05). The donor compartment flow-through diffusion cell was found to be a useful tool to evaluate the impact of salivary washout on mucoadhesive oral mucosal delivery systems.

The combined use of the lipophilic permeation enhancer, oleic acid together with polyethylene glycol 200 (PEG 200) as a co-enhancer and incorporated into the cubic liquid crystalline phase of glyceryl monooleate was investigated in the ex vivo buccal permeation of [D-Ala2, D-Leu5]enkephalin (DADLE) through porcine buccal mucosa mounted in a Franz cell. The addition of oleic acid (1%) and PEG 200 (1-10%) did not change the intact appearance of the cubic phase. PEG 200 increased the aqueous solubility of oleic acid incorporated into the cubic phase and hence promoted the transport of oleic acid into the porcine buccal mucosa. The solubilising effect of PEG 200 on oleic acid incorporated into the cubic phase was dependent on the PEG 200 concentration but was non-linear. The buccal permeation flux of DADLE significantly increased when 5% (P

The ex vivo buccal permeability of a [D-Ala(2), D-Leu(5)]enkephalin (DADLE) and glyceryl monooleate (GMO) was examined from the cubic and lamellar liquid crystalline phases of GMO and aqueous phosphate-buffered saline (pH 7.4, PBS) solution across excised porcine buccal mucosa mounted in a Franz cell. GMO was released in vitro from the liquid crystalline phases indicating the erosion of the liquid crystal matrices. GMO released from the liquid crystalline matrices permeated the porcine buccal mucosa with fluxes of 0.10+/-0.03 and 0.07+/-0.00%/cm(2) per h for the cubic and lamellar phases, respectively. The flux of DADLE (1.21+/-0.32 and 1. 15+/-0.11%/cm(2) per h for the cubic and lamellar phases, respectively) from the liquid crystalline phases was significantly enhanced by the GMO compared with PBS solution (0.43+/-0.08%/cm(2) per h) during the initial permeation phase (t3 h). Our results suggest that the cubic and lamellar liquid crystalline phases can be considered as promising buccal drug carriers for peptide drugs as well as acting as permeation enhancers.

The objective of the present study was to establish the method of measurement of hydrogen peroxide and to estimate the anti-oxidative effect of genistein in the skin. UVB induced skin oxidation and anti-oxidative effect of genistein formulations were evaluated by determining levels of hydrogen peroxide. The mechanism involved in the determination of hydrogen peroxide is based on a color reaction between ferric ion (Fe(3+)) and xylenol orange, often called FOX assay and subsequent monitoring of absorbance values of the reactant at 540 nm. The reaction was to some extent pH-dependent and detection sensitivity was greatest at pH 1.75. Genistein liposomal gel demonstrated better anti-oxidative effect with regard to lowering hydrogen peroxide levels elevated by UVB irradiation compared to genistein-suspended gel. A linear relationship has been observed between anti-oxidative effect of genistein and drug deposition in the skin tissue. Genistein liposomal gel resulting in the localization of the drug in the deeper skin led to improved anti-oxidative effect compared to genistein gel. The suggested method for evaluation of oxidation of the skin can be used as a tool to screen effective anti-oxidative agents and their delivery systems acting on the skin.

The impact of storage conditions on the permeability of porcine buccal mucosa to [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were obtained after the storage of the tissue intact in the pig heads at 4 degrees C or -20 degrees C, respectively, for 24 h. The results demonstrated that the barrier properties of the porcine buccal mucosa were maintained with regard to [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the tissue resulted in tissue damage illustrated by a significant increase in [3H]water permeability. [14C]Mannitol does not appear to be a suitable model solute to assess the ex vivo permeability of porcine buccal mucosa due to its extremely low permeability.