Usefulness of artificial membrane, strat-M®, in the assessment of drug permeation from complex vehicles in finite dose conditions

The ban on the use of animals in testing cosmetic products has led to the development of animal-free in vitro methods. Strat-M® is an artificial membrane engineered to mimic human skin and is recommended as a replacement for skin. However, its usefulness in the assessment of the permeation of cosmetics in in-use conditions remains unverified. No data have been published on its comparative performance with the membrane of choice, porcine skin. The comparative permeability characteristics of Strat-M® and porcine skin were investigated using Franz diffusion cells. Caffeine (CF) and rhododendrol (RD) in complex vehicles with varying concentrations of polyols were applied as finite and infinite doses. Good rank orders of permeation from finite dose experiments were observed for RD. High correlations were observed in RD permeation between Strat-M® and porcine skin under finite and infinite dose conditions, whereas only finite dose conditions for CF were associated with good correlations. Permeation from formulations with high polyol content and residual formulations was enhanced due to the disruption of the integrity of the Strat-M® barrier. The usefulness of Strat-M® in the assessment of dermal permeation may be limited to finite dose conditions and not applicable to infinite dose conditions or formulations applied in layers.11p. Article No.173 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Preparation, Characterization, Solubility, and Antioxidant Capacity of Ellagic Acid-Urea Complex

Ellagic acid (EA), a natural polyphenol found in berries, has high antioxidant capacity. This study aimed to improve EA solubility by complex formation with urea (UR) using solvent evaporation method and evaluate its solubility, antioxidant capacity, and physical properties. The solubility test (25 °C, 72 h) showed that the solubility of EVP (EA/UR = 1/1) was approximately two-fold higher than that of EA (7.13 µg/mL versus 3.99 µg/mL). Moreover, the IC50 values of EA and EVP (EA/UR = 1/1) (1.50 µg/mL and 1.30 µg/mL, respectively) showed higher antioxidant capacity of EVP than that of EA. DSC analysis revealed that the UR peak at 134 °C disappeared, and a new endothermic peak was observed at approximately 250 °C for EVP (EA/UR = 1/1). PXRD measurements showed that the characteristic peaks of EA at 2θ = 12.0° and 28.0° and of UR at 2θ = 22.0°, 24.3°, and 29.1° disappeared and that new peaks were identified at 2θ = 10.6°, 18.7°, and 26.8° for EVP (EA/UR = 1/1). According to 2D NOESY NMR spectroscopy, cross-peaks were observed between the -NH and -OH groups, suggesting intermolecular interactions between EA and UR. Therefore, complexation was confirmed in EA/UR = 1/1 prepared by solvent evaporation, suggesting that it contributed to the improvement in solubility and antioxidant capacity of EA.This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cite

Preparation, Characterization, and In Vitro Evaluation of Inclusion Complexes Formed between S-Allylcysteine and Cyclodextrins

The present study prepared inclusion complexes of S-allylcysteine (SAC) and cyclodextrin (α, β, γ) by the freeze-drying (FD) method and verified the inclusion behavior of the solid dispersion. Also, the study investigated the effect of SAC/CD complex formation on liver tumor cells. Isothermal titration calorimetry (ITC) measurements confirmed the exothermic titration curve for SAC/αCD, suggesting a molar ratio of SAC/αCD = 1/1, but no exothermic/endothermic reaction was obtained for the SAC/βCD and SAC/γCD system. Powder X-ray diffraction (PXRD) results showed that the characteristic diffraction peaks of SAC and CDs disappeared in FD (SAC/αCD) and FD (SAC/γCD), indicated by a halo pattern. On the other hand, diffraction peaks originating from SAC and βCDs were observed in FD (SAC/βCD). Near-infrared (NIR) absorption spectroscopy results showed that CH and OH groups derived from SAC and OH groups derived from αCD and γCD cavity were shifted, suggesting complex formation due to intermolecular interactions occurring in SAC/αCD and SAC/γCD. Stability test results showed that the stability was maintained with FD (SAC/αCD) over FD (SAC/βCD) and FD (SAC/γCD). In 1H–1H of NOESY NMR measurement, FD (SAC/αCD) was confirmed to have a cross peak at the CH group of the alkene of SAC and the proton (H-3, -5, -6) in the αCD cavity. In FD (SAC/γCD), a cross peak was confirmed at the alkyl group on the carbonyl group side of SAC and the proton (H-3) in the cavity of γCD. From the above, it was suggested that the inclusion mode of SAC is different on FD (SAC/CDs). The results of the hepatocyte proliferation inhibition test using HepG2 cells showed that FD (SAC/βCD) inhibited cell proliferation. On the other hand, FD (SAC/αCD) and FD (SAC/γCD) did not show a significant decrease in the number of viable cells. These results suggest that the difference in the inclusion mode may contribute to the stability and cell proliferation inhibition

Preparation and Characterization of a Hybrid Complex of Cyclodextrin-Based Metal—Organic Frameworks-1 and Ascorbic Acid Derivatives

Cyclodextrin-based metal–organic frameworks-1 (CD-MOF-1) prepared using potassium hydroxide, ethanol, and γ-cyclodextrin (γ-CD) has been reported as a new type of MOF for the development of pharmaceutical formulations. The present study aimed to investigate the physicochemical properties of ascorbic acid derivatives (L-ascorbyl 6-palmitate (ASCP); L-ascorbyl 2,6-palmitate (ASCDP)) complexed with CD-MOF-1 by a solvent evaporation method. Powder X-ray diffraction revealed that the crystal diffraction pattern of CD-MOF-1 changed from α-type to β-type when prepared by a solvent evaporation method. For ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4 evaporated samples, the crystal diffraction peaks derived from ASCP and ASCDP disappeared, indicating a β-like behavior. Differential scanning calorimetry results revealed that the endothermic peaks of evaporated samples (ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4) were not detected due to melting. Furthermore, intermolecular interactions were observed in the hydrogen bonds between the CH groups of the side chains of ASCP and ASCDP and the OH group of CD-MOF-1 in (ASCP/CD-MOF-1 = 1/2) and EVP (ASCDP/CD-MOF-1 = 1/4), based on the near-infrared absorption spectroscopy analysis. CD-MOF-1 did not form inclusion complexes with the lactone rings of ASCP and ASCDP, but with the lipophilic side chains. These results suggested that CD-MOF-1 may be useful in preparing novel drug carriers for ASCP and ASCDP.Article No.7309 This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cite

Determination of sugars and amino acids in japanese wine using core-shell liquid chromatography tandem electrochemical detection

In this study, sugars (glucose, fructose, and sucrose) and amino acids in plum and yuzu wines were quantified with a new and simple method involving an electrochemical detector (ECD) and core-shell column [S-30/70=St (styrene)/DVB (divinylbenzene)-5TMDAH (tetramethyldiaminohexane)]. Analysis was conducted under the following conditions: A column temperature (40°C), flow rate (0.3 mL/min), injection volume (20 μL), and mobile phase (0.1 mol/L NaOH). Glucose, fructose, and sucrose had retention times of 14.68 min, 16.22 min, and 19.29 min, respectively, when measured using an ECD. When the sugar content was compared among the plum wines, plum wine A had the lowest sugar content. A comparison of the sugar content of the different types of yuzu showed that yuzu wine C had the lowest sugar content. In addition, plum wine C showed higher values of amino acid components (2.27 μmol/mL of alanine, 0.67 μmol/mL of GABA, and 5.28 μmol/mL of glutamic acid) compared with A and B. This straightforward LC technique is reliable in the determination of carbohydrates and amino acid contents in wine, useful criteria for consumers in selecting wines parallel to their ideal health outcomes

Effect of layered application and finite dose conditions on the skin concentration and permeation of drugs

学位授与機関：城西大学 学位記番号：博甲第97号，学位の種別：博士（薬科学）， 学位授与年月日： 令和2年(2020年)3月17日 (75p.)博士（薬科学）城西大

Prolonged Distribution of Tranilast in the Eyes after Topical Application onto Eyelid Skin

Tranilast, a lipophilic drug with various ophthalmic applications, was used as a model drug to establish the possibility of delivering lipophilic drugs through the eyelid skin. Pharmacokinetics and tissue distribution studies were conducted employing three application methods (topical application onto eyelid skin, eye drops, and intravenous injection in rats) to broaden the significance of delivering drugs through the eyelids. A two-compartment open model analysis was used for intravenous route while a non-compartmental evaluation was used for topical applications to estimate the pharmacokinetic parameters. Eyelid skin application, eye drops, and intravenous administration had mean residence times (MRTs) of 8.07, 1.79, and 3.25 h in the eyeball and 10.8, 1.29, and 2.97 h in the conjunctiva, correspondingly. In the eyeball, topical application of tranilast onto the eyelids corresponded to a 4.5- and 2.5-fold higher MRT compared with eye drops and intravenous administration, respectively. An 8.4- or 3.6-fold higher MRT was observed in the conjunctiva after topical application compared with eye drops or intravenous administration, respectively. This indicated a gradual penetration of tranilast into the eyeball and conjunctiva, subsequently a slow elimination from these target tissues.U813230009<Pre 医中誌

Halal Cosmetics: A Review on Ingredients, Production, and Testing Methods

The demand for halal cosmetic products among the 2.4 billion Muslim consumers worldwide is increasing. However, the demand for halal cosmetics remains unmet because cosmetics production is dominated by non-halal cosmetic manufacturers, whose production methods may not conform with the requirements of halal science. The development of halal cosmetics and the assessment of their product performance is still in its infancy. The integration of halal science in the manufacture of most cosmetic products remains inadequate. Moreover, there is a global dearth of guiding documents on the development and assessment techniques in the production of comprehensively halal cosmetics. This paper aims to abridge existing literature and knowledge of halal and cosmetic science in order to provide essential technical guidance in the manufacture of halal cosmetics. In addition, the adoption of these methods addresses the unique ethical issues associated with conformance of cosmetics’ product performance to religious practices and halal science. It highlights the applicability of established methods in skin science in the assessment of halal cosmetics.Article No.37. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cite

Prediction of skin permeation and concentration of rhododendrol applied as finite dose from complex cosmetic vehicles

Finite dose experiments represent clinical use wherein depletion of dose, evaporation of excipients, and gradual change in vehicle composition may occur. In the present study, we attempted a mathematical approach for predicting skin permeation and concentration of a cosmetic active, rhododendrol (RD), from complex vehicle-based formulations applied in finite dose. In vitro skin permeation and concentration studies of RD were conducted from formulations containing water and polyols with concentrations ranging from 10 to 100% under infinite and finite dose conditions using vertical Franz diffusion cells. Observed data for skin permeation and the viable epidermis and dermis (VED) concentration of RD were estimated by the differential equations under Fick’s second law of diffusion together with water evaporation kinetics and changes in the partition coefficient from vehicles to the stratum corneum. As a result, a goodness-of-fit was observed allowing accurate estimation of skin permeation and VED concentration of RD. This mathematical approach could become a useful tool to estimate the skin permeation and concentration of actives from topical formulation applied in finite dose conditions likened in actual use.Article 11918

Preparation and Characterization of a Hybrid Complex of Cyclodextrin-Based Metal—Organic Frameworks-1 and Ascorbic Acid Derivatives

Cyclodextrin-based metal–organic frameworks-1 (CD-MOF-1) prepared using potassium hydroxide, ethanol, and γ-cyclodextrin (γ-CD) has been reported as a new type of MOF for the development of pharmaceutical formulations. The present study aimed to investigate the physicochemical properties of ascorbic acid derivatives (L-ascorbyl 6-palmitate (ASCP); L-ascorbyl 2,6-palmitate (ASCDP)) complexed with CD-MOF-1 by a solvent evaporation method. Powder X-ray diffraction revealed that the crystal diffraction pattern of CD-MOF-1 changed from α-type to β-type when prepared by a solvent evaporation method. For ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4 evaporated samples, the crystal diffraction peaks derived from ASCP and ASCDP disappeared, indicating a β-like behavior. Differential scanning calorimetry results revealed that the endothermic peaks of evaporated samples (ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4) were not detected due to melting. Furthermore, intermolecular interactions were observed in the hydrogen bonds between the CH groups of the side chains of ASCP and ASCDP and the OH group of CD-MOF-1 in (ASCP/CD-MOF-1 = 1/2) and EVP (ASCDP/CD-MOF-1 = 1/4), based on the near-infrared absorption spectroscopy analysis. CD-MOF-1 did not form inclusion complexes with the lactone rings of ASCP and ASCDP, but with the lipophilic side chains. These results suggested that CD-MOF-1 may be useful in preparing novel drug carriers for ASCP and ASCDP