Effects of some hydrophilic permeation enhancers on the absorption of bepridil through excised human skin

The permeation of Bepridil through excised human skin was measured from vehicles composed of various mixtures of aqueous buffer and the permeation enhancers ethanol, DMSO or DMF. Only DMSO was found to act as a true permeation enhancer for the drug, the magnitude of its action depending on its concentration in the vehicle. At concentrations greater than 50% DMSO the permeability coefficient of the drug was increased over and above that which could be accounted for by changes in partitioning of the drug between vehicle and skin. The effects of ethanol could be related to changes in the measured skin/vehicle partition coefficients of the drug. DMF showed a complicated, concentration dependent influence on permeation.     

Effects of some hydrophilic permeation enhancers on the absorption of bepridil through excised human skin

Abstract

The permeation of Bepridil through excised human skin was measured from vehicles composed of various mixtures of aqueous buffer and the permeation enhancers ethanol, DMSO or DMF. Only DMSO was found to act as a true permeation enhancer for the drug, the magnitude of its action depending on its concentration in the vehicle. At concentrations greater than 50% DMSO the permeability coefficient of the drug was increased over and above that which could be accounted for by changes in partitioning of the drug between vehicle and skin. The effects of ethanol could be related to changes in the measured skin/vehicle partition coefficients of the drug. DMF showed a complicated, concentration dependent influence on permeation.     

In vitro percutaneous absorption of genistein from topical gels through human skin

The objective of this study was to formulate genistein as a topical gel with various penetration enhancers for increased permeation and retention in human skin. The high performance liquid chromatography assay method was validated for precision and reproducibility. The intra-day and inter-day precision as represented by the coefficient of variation (CV) of the peak areas were <0.44% and <0.67%, respectively. Further, the reproducibility was demonstrated by the CV of the assay at different genistein concentrations, which were <1.64%. Genistein was subjected to various stress conditions to obtain basic information on the appropriate pH and aqueous vehicle for formulating topical gels. Genistein was highly stable under neutral and oxidative conditions, but degraded to highly polar and nonpolar compounds under basic and acidic conditions, respectively. Menthol produced a 9- and 22-fold increase in the flux and skin retention of genistein, respectively, after 24?h of gel application as compared with the control (no enhancer). Cineole showed an approximately 7-fold increase in flux, but skin retention did not increase significantly. Transcutol increased the flux and skin retention of genistein by 5- and 7-fold, respectively. When Transcutol was formulated with Lauroglycol, there was a 13- and 9-fold increase in the flux and skin retention, respectively. Incorporation of penetration enhancers into the topical gel increased the skin permeation of genistein, so that the target delivery rate for its therapeutic effects can be achievable based on the in vitro human skin data generated in this study.     

In vitro percutaneous absorption of genistein from topical gels through human skin

The objective of this study was to formulate genistein as a topical gel with various penetration enhancers for increased permeation and retention in human skin. The high performance liquid chromatography assay method was validated for precision and reproducibility. The intra-day and inter-day precision as represented by the coefficient of variation (CV) of the peak areas were <0.44% and <0.67%, respectively. Further, the reproducibility was demonstrated by the CV of the assay at different genistein concentrations, which were <1.64%. Genistein was subjected to various stress conditions to obtain basic information on the appropriate pH and aqueous vehicle for formulating topical gels. Genistein was highly stable under neutral and oxidative conditions, but degraded to highly polar and nonpolar compounds under basic and acidic conditions, respectively. Menthol produced a 9- and 22-fold increase in the flux and skin retention of genistein, respectively, after 24?h of gel application as compared with the control (no enhancer). Cineole showed an approximately 7-fold increase in flux, but skin retention did not increase significantly. Transcutol increased the flux and skin retention of genistein by 5- and 7-fold, respectively. When Transcutol was formulated with Lauroglycol, there was a 13- and 9-fold increase in the flux and skin retention, respectively. Incorporation of penetration enhancers into the topical gel increased the skin permeation of genistein, so that the target delivery rate for its therapeutic effects can be achievable based on the in vitro human skin data generated in this study.     

Chemical enhancers for the absorption of substances through the skin: Laurocapram and its derivatives

Absorption enhancers are substances used for temporarily increasing a membrane's permeability (e.g., the skin and mucosa), either by interacting with its components (lipids or proteins) or by increasing the membrane/vehicle partition coefficient. This article presents the results of biophysical and permeability studies performed with Laurocapram and its analogues. As shown, Laurocapram and its analogues present different enhancing efficacies, for most of both hydrophilic and lipophilic substances. The enhancing effect of Laurocapram (Azone) is attributed to different mechanisms, such as insertion of its dodecyl group into the intercellular lipidic bilayer, increase of the motion of the alkylic chains of lipids, and fluidization of the hydrophobic regions of the lamellate structure. Toxicological studies reveal a low toxicity for Laurocapram, and for some derivatives, a relationship exists between toxicity and the number of carbons in the alkylic chain. Very important, when applied to human skin, Laurocapram shows a minimal absorption, being quickly eliminated from circulation. However, although Laurocapram and its derivatives have been shown to provide enhancement, they have not been widely accepted because of their suspected pharmacological activity or questions about their safety.     

Percutaneous transport of diclofenac sodium from mixtures of fatty alcohol (or fatty acid) and propylene glycol through the rabbit abdominal skin

Diclofenac sodium is a nonsteroidal anti-inflammatory drug with analgesic, antipyretic, and anti-inflammatory activity. When used in a topical application, diclofenac can diffuse through the skin and into the subcutaneous tissue to effect the anti-inflammatory action. In this study, in vitro evaluations of the percutaneous transport of diclofenac sodium in various bases containing fatty alcohols/propylene glycol or fatty acid/propylene glycol mixtures through the abdominal skin of the rabbit were investigated. Results show that the transdermal flux of diclofenac sodium in the fatty alcohol/propylene glycol bases of the same ratio is affected by the chain length of the fatty alcohol, and its effect is in the order of C10 > C12 > C14 > C18. However, the transdermal flux of diclofenac sodium in the fatty acid/propylene glycol bases of the same ratio is also affected by the chain length of the fatty acid, but no absolute relationship was found. For the same chain length of fatty acid and fatty alcohol used in the formulation base that was otherwise the same, the transdermal flux of diclofenac sodium is higher in the formula containing fatty alcohol than that containing fatty acid.     

Effect of urea and pantothenol on the permeation of progesterone through excised rat skin from polymer matrix systems

Standard in vitro permeation experiments, using excised rat skin, were carried out to establish the release profile and permeation behavior of progesterone from polymethacrylate (PMA), polyvinylpyrrolidon (PVP), and polyvinylalcohol (PVA) transdermal systems. Data obtained show significant differences in release characteristics from each polymer systems. The greatest amount of progesterone was released from the PVA system. The influence of urea and pantothenol on progesterone release was also investigated. Release data were compared with the permeation rates of progesterone across excised rat skin. The highest permeation rates were measured from PVA matrices containing 5% urea (860 ± 138 μg/cm²; cumulative amount permeated in 24 hr) and from PVP matrices containing 6% pantothenol (660 ± 73 μg/cm²; cumulative amount permeated in 24 hr). A good correlation between release and permeation data was found with the polymer matrices; however, this was not the case when additives were included.     

In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures

The effect of cellulose ether polymer mixtures, containing both hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC K15M or K100M), on ketoprofen (KTP) release from matrix tablets was investigated. In order to evaluate the compatibility between the matrix components, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) experiments were performed. The results evidence the absence of significant intermolecular interactions that could eventually lead to an incompatibility between the drug and the different excipients. Formulations containing mixtures of polymers with both low and high viscosity grades were prepared by a direct compression method, by varying the polymer/polymer (w/w) ratio while keeping the drug amount incorporated in the solid dispersion constant (200?mg). The hardness values of different matrices were found within the range 113.8 to 154.9 N. HPLC analysis showed a drug content recovery between 99.3 and 102.1%, indicating that no KTP degradation occurred during the preparation process. All formulations attained a high hydration degree after the first hour, which is essential to allow the gel layer formation prior to tablet dissolution. Independent-model dissolution parameters such as t_10% and t_50% dissolution times, dissolution efficiency (DE), mean dissolution time (MDT), and area under curve (AUC) were calculated for all formulations. Zero-order, first-order, Higuchi, and Korsmeyer–Peppas kinetic models were employed to interpret the dissolution profiles: a predominantly Fickian diffusion release mechanism was obtained – with Korsmeyer–Peppas exponent values ranging from 0.216 to 0.555. The incorporation of HPC was thus found to play an essential role as a release modifier from HPMC containing tablets.     

Transdermal absorption of natural progesterone from alcoholic gel formulations with hydrophilic surfactant

Objectives: The aim of this study was to evaluate the in vitro skin permeation and in vivo transdermal absorption of natural progesterone (Prog) from alcoholic gel-based transdermal formulations containing Prog dissolved stably at a concentration of 3%.

Methods: 3% Prog dissolved gel formulations were prepared containing with water, ethanol, 1,3-butylene glycol, carboxyvinylpolymer, diisopropanolamine, polyoxyethylene (2) oleylether and benzyl alcohol. The gel formulations added different hydrophilic surfactants and isopropyl myristate or propylene glycol dicaprylate (PGDC) as oily solvents were applied in vitro permeation study through excised rat skin on unocclusive condition. The gel formulations added polyoxyethylene (20) oleylether (Oleth-20) as hydrophilic surfactant and PGDC were applied in vivo single- and repeated-dose transdermal absorption study of rat on unocclusive condition.

Results: The results of evaluation of the gel formulations by an in vitro skin permeation study revealed a high flux of Prog from the formulation containing Oleth-20 and Oleth-20 with PGDC. The results of single and repeated in vivo transdermal absorption studies confirmed that good plasma levels of Prog were achieved and maintained by Oleth-20 and PGDC containing gel formulation.

Conclusions: The Oleth-20 and PGDC containing ethanolic gel formulation seemed to have the ability to maintain a high activity of Prog and high diffusivity or solubility of Prog in the epidermis on the practical formulation application.     

Evaluation of the percutaneous absorption of chlorpromazine from PLO gels across porcine ear and human abdominal skin

Objective: The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life.

Methods: PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (C_ss) of chlorpromazine was calculated from the flux values.

Results: The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical C_ss of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50?ng/ml, respectively. PLO gels only marginally increased the flux and theoretical C_ss of chlorpromazine.

Conclusion: From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.     

Percutaneous absorption of metopimazine and effect of cyclodextrins

Metopimazine (MPZ) is used to prevent emesis during chemotherapies. A transdermal delivery system of MPZ may present a great advantage in patients to improve compliance. Hydroxypropyl beta cyclodextrin (HPbetaCD) and partially methylated beta cyclodextrin (PMbetaCD) were tested to enhance the percutaneous absorption of MPZ through pig skin using Franz's cells. The MPZ hydrochloride flux was low with 0.176 +/- 0.054 microg/h/cm(2) and no flux was detected with a suspension of MPZ (base). The used characterization analyses demonstrated the formation of an inclusion complex with cyclodextrin and this complex improved percutaneous absorption of MPZ. Flux was increased to 0.240 +/- 0.032 microg/h/cm(2) and 0.566 +/- 0.057 mug/h/cm(2) for HPbetaCD and PMbetaCD, respectively, with a concentration of 20%. This study has shown that HPbetaCD and PMbetaCD improved the percutaneous penetration of MPZ. Cyclodextrin complexes increased MPZ bioavailability at the skin surface and PMbetaCD was also able to extract cutaneous fatty acids.     

Formulation and characterization of a captopril ethyl ester drug-in-adhesive-type patch for percutaneous absorption

Background: The ethyl ester of captopril has been shown to exhibit enhanced permeation across human skin compared to the parent drug. A drug-in-adhesive patch formulation of a captopril ethyl ester was therefore developed for optimum drug release. Method: A wide range of transdermal patches were prepared using two commercially available bioadhesive polymers. Investigational screening was conducted on the patches using microscopy, texture profile analysis, and infrared spectroscopy. Drug release profiles of suitable patches were obtained using both polydimethylsiloxane (Silastic?) and porcine skin in vitro. Results: Diffusion results across Silastic? showed a gradual plateau in flux with increased drug loading that may be attributable to intramolecular interactions while flux across porcine skin was seen to increase with increasing patch thickness and attained a therapeutic level. Conclusions: This study demonstrated that adhesion and drug loading are significant factors in optimizing a topical patch formulation for the delivery of a captopril prodrug.     

聚环氧乙烷及其衍生物在超滤膜亲水化改性中的应用

依据亲水改性方法的划分从膜的表面涂覆、共混、表面接枝和成膜材料改性等4个方面进行阐述,分析比较了聚环氧乙烷及其衍生物在各种不同的疏水超滤膜亲水改性中应用的途径和特性。经过聚环氧乙烷及其衍生物改性之后,超滤膜的接触角降低,蛋白质吸附量减少,亲水性和抗污染能力明显提高,应用前景更加广阔。     

In-vitro release studies op chlorpheniramine maleate from topical bases using cellulose membrane and hairless mouse skin

Abstract

In-vitro release of chlorpheniramine maleate from various topical bases was studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included a polymer gel base, a modified hydrophilic ointment base and a modified petrolatum base. The effects of the additive ingredients, such as, urea, ethanol and dimethylsulfoxide (DMSO) on the drug release were also investigated. The rank order of drug release through the cellulose membrane was observed to be: the gel base > the modified hydrophilic ointment base > the modified hydrophilic petrolatum base. In general, the presence of additives adversely affected the drug release except for the (DMSO) and ethanol in certain cases.

The samples with maximum drug release through the cellulose membrane were further studied for the drug release using hairless mouse skin as the diffusion barrier. Here again, the gel base gave the best in-vitro release of the drug, and the data correlated well with the results obtained through the cellulose membrane. These data were treated with various kinetic principles to determine the relevant parameters, such as, the steady state flux, the diffusion coefficient and the permeability coefficient etc. Using these information, the samples were evaluated for delivering drug via diadermatic dosage form.     

石墨烯-羧甲基纤维素复合气凝胶的制备及吸油性能评价EI北大核心CSCD

以氧化石墨(GO)为主要原料,并引入高分子羧甲基纤维素(CMC),采用水热还原结合冰模板的方法,经常压干燥和疏水改性,制备石墨烯-羧甲基纤维素复合气凝胶(HGA/CMC)。通过SEM、FT-IR、XPS、电子万能试验机等手段对该气凝胶进行表征,证明了GO与CMC的有效复合和疏水改性的成功。将HGA/CMC用于油品吸附,结果表明:HGA/CMC可利用其丰富的孔道结构吸附纯油品,对油品的吸附量在70.28~172.78 g·g^(-1),且油品密度越大,单位质量气凝胶可吸附的油品质量越大。此外HGA/CMC能选择性地吸附水上浮油、水底重油并高效分离水中乳化油,且通过机械挤压可实现HGA/CMC的循环再生利用,10次挤压再生后其吸附量仅损失15%,是具有应用潜力的含油污水治理材料。     

Excited-state absorption and anisotropy properties of two-photon absorbing fluorene derivatives

The electronic structure of fluorene derivatives N-(7-benzothiazol-2-yl-9,9-bis-decyl-9H-fluoren-2-yl)-acetamide (1); 9,9-didecyl-2,7-bis-(N,N-benzothiazoyl)fluorene (2); 4,4'-{[9,9-bis(ethyl)-9H-fluorene-2,7-diyl]di-2,1-ethenediyl}bis(N,N-diphenyl)benzeneamine (3); and 4,4',4"{[9,9-bis(ethyl)-9H-fluorene-2,4,7-triyl]tri-2,1-ethenediyl}tris(N,N-diphenyl)benzeneamine (4) were investigated by a steady-state spectral technique, quantum-chemical calculations, and a picosecond pump-probe method. These derivatives are of interest for their relatively high two-photon absorption. The steady-state excitation anisotropy spectra reveal the nature of the ground-state absorption bands. Semiempirical quantum-chemical calculations of the fluorene derivatives (AM1, ZINDO/S) show good agreement with experimental data. The spectral positions and alignment of various electronic transitions of derivatives 1-4 were estimated from their excited-state absorption and anisotropy spectra.     

In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin

The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.     

Release profiles of theophylline from microspheres consisting of dextran derivatives and cellulose acetate butyrate: effect of polyion complex formation

The objective of this study was to evaluate the utility of mixtures among oppositely charged dextran derivatives as constituents of a controlled release microsphere. Carboxymethyldextran (CMD) and dextran sulfate (DS) were used as polyanions, and [2-(diethylamino) ethyl] dextran (EA) and [2-hydroxypropyltrimethylammonium] dextran (CDC) as polycations. The microspheres consisting of hydrophilic and hydrophobic polymers were prepared by emulsion-solvent evaporation method. The mixtures, CMD/EA, CMD/CDC, DS/EA, and DS/CDC, were used as hydrophilic polymers, because they can interact with each other to form polyion complexes for the improvement of sustained-release performances. Cellulose acetate butyrate and theophylline were used as a model hydrophobic polymer and a model drug, respectively. The yield of microspheres was excellent (more than 95%). According to observation, by scanning election microscopy (SEM) microspheres were spherical with a rough surface. The in vitro drug release from microspheres was examined in the JP XIV first fluid, pH 1.2, and second fluid, pH 6.8, at 37°C, and 100 rpm. In the DS/CDC system, drug release was depressed by formation of a polyion complex and not affected by pH of dissolution medium. The release rate was modulated by the ratio of hydrophilic and hydrophobic matrix. This particulate system, in which the polyion complex matrix is strengthened by a hydrophobic polymer, is a promising formulation for drug delivery.