ABSTRACT
The percutaneous penetration-enhancing effects of glycolic acid, lactic acid and sodium lauryl sulphate through the human epidermis was investigated using 5-fluorouracil as a hydrophilic model permeant and three compounds belonging to the phenylalcohols: 2-phenyl-ethanol, 4-phenyl-butanol and 5-phenyl-pentanol. The lipophilicity values of the compounds ranged from log Poct -0.95 to 2.89. The effect of the enhancer concentration was also studied. Skin pretreatment with aqueous solutions of the three enhancers did not increase the permeability coefficient of the most lipophilic compound (log Poct = 2.89). For the other compounds assayed, the increase in the permeability coefficients depended on the concentration used in skin pretreatment, and on the lipophilicity of the compounds tested-and was always greater for the most hydrophilic compound (5-fluorouracil), for which lactic acid exerted a greater enhancer effect than glycolic acid or sodium lauryl sulphate. Primary irritation testing of the three enhancers was also carried out at the two concentrations used in skin pretreatment for diffusional experiments (1% and 5%, w/w). The least irritant capacity corresponded to lactic acid; consequently, this alpha-hydroxyacid could be proposed as a percutaneous penetration enhancer for hydrophilic molecules that are of interest for transdermal administration.
Subject(s)
Alcohols/pharmacokinetics , Fluorouracil/pharmacokinetics , Hydroxy Acids/pharmacology , Skin Absorption , Skin/drug effects , Adult , Butanols/pharmacokinetics , Epidermis/drug effects , Female , Glycolates/pharmacology , Humans , In Vitro Techniques , Lactic Acid/pharmacology , Pentanols/pharmacokinetics , Permeability , Phenylethyl Alcohol/pharmacokinetics , Skin/metabolism , Sodium Dodecyl Sulfate/pharmacologyABSTRACT
Se ha estudiado el comportamiento bioadhesivode un gel de Carbopol 971-P, en presenciade diferentes concentraciones de propilenglicol(10%, 30%, 50%, 70%, m/m). A partir delas curvas fuerza-desplazamiento se han calculadola fuerza máxima y el trabajo de adhesión.El estudio comparativo de los valores mediosdel trabajo de adhesión indica que noexisten diferencias significativas (P<0,05) entreel hidrogel de Carbopol 971-P sin propilenglicol(control) y los hidrogeles adicionados depropilenglicol a las concentraciones más elevadas(10 y 30%, respectivamente). Se concluyeque, cuando se pretende utilizar Carbopol971-P en preparaciones adhesivas para la administraciónde fármacos de baja hidrosolubilidad,es posible incrementar la concentraciónde fármaco disuelto en el sistema bioadhesivo,mediante la incorporación de propilenglicol enconcentraciones de hasta un 30% (m/m), sinque se modifique significativamente su capacidadbioadhesiva
The influence of different concentrations ofpropylene glycol (10%, 30%, 50%, 70%, w/w)on the properties of bioadhesion of Carbopol971-P gels has been analyzed. From force-deformationcurves, the peak force and the tensilework have been calculated. The comparativestudy of the mean values of tensile work indicatethat no significant differences (P<0.05) existamong the Carbopol 971-P hydrogels withoutpropylene glycol (control) and with propyleneglycol for the lowest concentrations (10 and30%, respectively). Therefore, it seems possibleto use Carbopol 971-P hydrogels addedwith propylene glycol until a concentration of30% (w/w), in order to increase drug solubility,without significant modification of its capacityof bioadhesion
Subject(s)
Drug Industry/methods , Biological Availability , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Solubility , Drug Industry/organization & administration , Drug Delivery Systems/classification , Drug Delivery Systems/trendsABSTRACT
Los sistemas lipídicos nanoparticulares (SLN) representan una excelente alternativa a los diferentes sistemas transportadores de ingredientes activos de tamaño coloidal: microemulsiones, liposomas y micro- y nanopartículas poliméricas. Los SLN se han utilizado tanto en el campo farmacéutico como en el cosmético. Las ventajas que proporcionan cuando se utilizan para la administración tópica de principios activos, son evidentes: protección de compuestos lábiles frente a la degradación química, control de la liberación de ingredientes activos, desarrollo de un efecto oclusivo y un efecto barrera frente a las radiaciones ultravioleta. No obstante, presentan algunos incovenientes como su capacidad de carga limitada y la posible liberación súbita "efecto burst" del principio activo durante el período de almacenamiento. En esta revisión se analiza la composición, el método de elaboración por homogeneización de presión elevada, los mecanismos implicados en la liberación y las aplicaciones de estos sistemas en el campo de los preparados dermatológicos (AU)
Subject(s)
Humans , Dermatologic Agents , Cosmetics , Lipids , Preparation Scales , Drug Compounding/methods , Drug StorageABSTRACT
El etanol, junto con otros alcoholes, solos o en soluciones hidroalcohólicas en distintas proporciones, son sustancias muy utilizadas en la industria farmacéutica, sea como excipientes en diversos preparados farmacéuticos, o como disolventes. En las mezclas alcohol-agua se produce el fenómeno sobradamente conocido de la contracción de volumen; pero este fenómeno se acompaña de un considerable incremento de la viscosidad de la mezcla que se atribuye al aumento del tamaño del paquete molecular como consecuencia de la solvatación o formación de puentes de hidrógeno entre el etanol y el agua; el fenómeno recibe el nombre de sinergia viscosa. La contracción de volumen es un fenómeno que está reflejado y cuantificado en la bibliografía, cosa que no ocurre con el hecho del aumento de viscosidad, por lo que el objetivo del presente trabajo es el estudio cuantitativo de dicha sinergia y su relación con el aumento de densidad, así como su variación con la temperatura (AU)
Subject(s)
Water/chemistry , Water/pharmacology , Water Viscosity , Ethanol/chemical synthesis , Alcohols/pharmacology , Alcohols/chemical synthesisABSTRACT
Recently we have proved that Span 20 has the same enhancer effect as Azone on in vitro percutaneous penetration of lipophilic compounds (logP(oct) from 1.34 to 2.33). The purpose of this work is to study the interactions of Span 20 with stratum corneum lipids monolayers and to compare them with Azone. The surface pressure-area characteristics of Span 20 in mixed monolayers with different model lipids (ceramides, cholesterol, free fatty acids and two mixtures of ceramides+cholesterol, and ceramides+cholesterol+free fatty acids) in similar proportions to that which exists in human stratum corneum lipids were recorded as compression isotherms at 25 degrees C. Azone was also investigated on monomolecular films of some of these lipids. The results indicate that the effect exerted upon lipid packing by the Span 20 correspond, as in the case of Azone, to increased fluidity within monolayers. To quantify and compare the effect of Span 20 and Azone, the compressibility of enhancer-lipid model mixed monolayers was calculated, and expressed as a function of mole fraction of enhancer present on the films. Statistical comparison of the results obtained from both enhancers shows that they are equally potent in their interaction with the lipid models assayed. These models, if restricted, seem to be good for predict the activity and potency of percutaneous enhancers on the fluididity of the lipidic structure of the stratum corneum.
Subject(s)
Azepines/pharmacology , Epidermis/drug effects , Hexoses/pharmacology , Lipids/analysis , Skin Absorption/drug effects , Animals , Cattle , Ceramides/analysis , Cholesterol/analysis , Epidermis/chemistry , HumansABSTRACT
Generally, the mechanisms of percutaneous absorption are studied from correlations between representative penetration parameters (permeability coefficients) and variables accounting for lipophilicity or other related physicochemical properties. The present study was developed on the basis of the in vitro permeability coefficients through human skin, 280 microns in thickness, of a non-ionic homologous series of compounds (phenylalkanols). The corresponding penetration/lipophilicity correlations were compared with those found for a basic homologous series (4-n-alkylanilines) through a membrane of similar characteristics. The in vitro behaviour of both series of compounds may be regarded as similar. Differences were only observed in the permeability coefficients of those elements which in both series exhibited lipophilicity values above that considered optimum, as predicted by the selected biophysical penetration model. Consequently, it appears that the removal of the thick dermal tissue leads to increased permeation rates for the more lipophilic compounds and suggests that the dermis acts as an aqueous matrix.
Subject(s)
Skin Absorption/physiology , Chemical Phenomena , Chemistry, Physical , Diffusion Chambers, Culture , Humans , In Vitro Techniques , PermeabilityABSTRACT
Sequential determinations of serum enolase and pyruvate kinase (PK) activities were carried out in addition to routine enzyme assays on 191 patients admitted to a coronary care unit. The upper reference values established in 61 healthy laboratory staff members were 21 U/1 for enolase and 76 U/1 for PK. Of 99 patients with a confirmed diagnosis of myocardial infarction (MI), 97 manifested raised serum enolase during the period of observation; 85 of these patients had raised serum PK. The incidence of raised values for serum PK among patients considered not to have sustained infarction was similar to that shown by the routine enzymes, but serum enolase activity was much more frequently raised in these patients. The time-course of elevation of serum enolase and also that of PK are discussed in relation to the changes in other serum enzymes routinely measured for MI.
Subject(s)
Myocardial Infarction/diagnosis , Phosphopyruvate Hydratase/blood , Pyruvate Kinase/blood , Clinical Enzyme Tests , Coronary Disease/diagnosis , Diagnosis, Differential , Evaluation Studies as Topic , Humans , MethodsABSTRACT
An antiserum raised in the chicken against purified rat skeletal muscle enolase neutralized 86% of the enolase activity of human heart muscle and 8.7% +/- 4.8% (mean +/- S.D.) of the enolase activity in normal human serum. The fraction of enolase inhibited by the antiserum, designated as 'immunologically reacting muscle enolase', promptly rose after myocardial infarction in the serum of affected subjects, reaching peak values in excess of 40% in all but one of 23 subjects. Only one subject with ischaemic heart disease, but without infarction, and 2 with miscellaneous conditions, among 117 such patients tested, yielded comparable values. The test appears to be highly specific for myocardial infarction when muscle disease can be excluded and would not be difficult to introduce as a laboratory routine.
