The availability of a drug from a topical preparation is dependent on many factors, one of the most important being the composition of the vehicle. Glycerol, propylene glycol and polyethylene glycol 200 are widely used as ingredients in topical formulations. The aim of this study was to examine how these glycols affected some of the fundamental factors involved in percutaneous absorption of ethyl- methyl- and glycol salicylate. To do this, certain drug-vehicle, drug-vehicle-skin and vehicle-skin interactions were investigated. Drug-vehicle interactions were evaluated using solubility - and rheological measurements, equilibrium dialysis, diffusion coefficient - and release rate determinations. In particular, the study showed that it is important to consider the viscosity contribution of a cosolvent to the vehicle and that it is essential not to over solubilise a drug in the vehicle. The evaluation of drug-vehicle-skin interactions involved both in vitro and in vivo determinations. The in vitro study consisted of solubility- and partition coefficient measurements together with determination of diffusion coefficients and penetration rates for the drugs and the glycols using a two compartment cell in which nude mouse skin was the rate controlling barrier. In vivo, the concentrations of the glycols were determined in the individual layers in the skin and in the plasma of nude mice. The flux of the salicylates was largely unaffected by the various solvent concentrations and the different solvents, except when high concentrations of propylene glycol and glycerol were employed. The measurements of glycerol and propylene glycol in the skin and plasma suggested that the amount of the glycols penetrating into the skin from a topical application were unlikely to have any effect on the partition coefficient of a drug between the vehicle and the skin or the diffusivity of the drug in the skin phase. A comparison of the in vivo and in vitro results indicated a good correlation between these studies. In vivo and in vitro histological assessment were employed to evaluate vehicle-skin effects. Applications of glycerol and PEG 200 had no effect on the skin, whereas increasing concentrations of propylene glycol caused progressive disintegration of the stratum corneum. Some `penetration enhancers' showed unacceptable levels of skin damage and/or irritancy. Future studies may correlate these findings with their penetration enhancing properties.

No description available.

O objetivo do presente trabalho foi de analisar, experimentalmente, a variação do índice de transmissão e o coeficiente de atenuação ultra-sônica no meio diclofenaco gel, bem como, a penetração do fármaco em amostras de gelatina semelhante a pele humana através da fonoforese. A variação destes parâmetros foi investigada em 120 amostras de agar-agar, (modo contínuo, 1 MHz de freqüência, nas intensidades de 1,0 e 1,5 W/\'CM POT.2\'), por 5 minutos. Os corpos de prova forma divididos em grupos referentes as intensidades de ultra-som utilizadas, e cada um destes grupos, foi subdividido em sub-grupos correspondendo aos diferentes meios utilizados para irradiação. A investigação da transmissão ultra-sônica foi medida a partir de um dosímetro de precisão ULTRASONIC POWER METER, modelo UPM-DT 10. O cálculo do coeficiente de atenuação foi realizado a partir dos dados de leitura da transmissão ultra-sônica. A penetração ou não da droga foi estudada por análise macroscópica e microscópica. Segundo os resultados obtidos não houve variação significativa nos índices de transmissão e nos coeficientes de atenuação do diclofenaco gel em comparação ao gel neutro. A penetração do medicamento foi de 3 mm para as amostras irradiadas com a intensidade de 1,0 W/\'CM POT.2\' e de 5 mm para as amostras irradiadas com 1,5 W/\'CM POT.2\', não houve evidência de penetração do fármaco no grupo controle. Os resultados obtidos neste estudo sugerem que a fonoforese do diclofenaco gel é efetiva nas intensidades 1,0 e 1,5 W/\'CM POT.2\'. / The objective of the present work was of analyzing, experimentally, the variation of the transmission index and the coefficient of ultrasonic reduction in the half diclofenaco gel, as well as, the penetration of the drug in samples of similar jelly the human skin through the phonophoresis. The variation of these parameters was investigated in 120 agar-agar samples, (continuous way, 1 MHz of frequency, in the intensities of 1,0 and 1,5 W/\'CM POT.2\'), for 5 minutes. The proof bodies form divided in referring groups the ultrasound intensities used, and each one of these groups, it was subdivided in sub-groups corresponding to the different means used for irradiation. The investigation of the ultrasonic transmission was measured starting from a ULTRASONIC POWER METER, model UPM-DT 10. The calculate it of the reduction coefficient was accomplished starting from the data of reading of the ultrasonic transmission. The penetration or not of the drug it was studied for it analyzes macroscopic and microscopic. According to the obtained results there was not significant variation in the transmission indexes and in the coefficients of reduction of the diclofenaco gel in comparison with the neutral gel. The penetration of the medicine went of 3 mm to the samples irradiated with the intensity of 1,0 W/\'CM POT.2\' and of 5 mm for the samples irradiated with 1,5 W/\'CM POT.2\', there was not evidences of penetration of the drug in the group control. The results obtained in this study suggest that the phonophoresis of the diclofenaco gel is effective in the intensities 1,0 and 1,5 W/\'CM POT.2\'.

O objetivo do presente trabalho foi de analisar, experimentalmente, a variação do índice de transmissão e o coeficiente de atenuação ultra-sônica no meio diclofenaco gel, bem como, a penetração do fármaco em amostras de gelatina semelhante a pele humana através da fonoforese. A variação destes parâmetros foi investigada em 120 amostras de agar-agar, (modo contínuo, 1 MHz de freqüência, nas intensidades de 1,0 e 1,5 W/\'CM POT.2\'), por 5 minutos. Os corpos de prova forma divididos em grupos referentes as intensidades de ultra-som utilizadas, e cada um destes grupos, foi subdividido em sub-grupos correspondendo aos diferentes meios utilizados para irradiação. A investigação da transmissão ultra-sônica foi medida a partir de um dosímetro de precisão ULTRASONIC POWER METER, modelo UPM-DT 10. O cálculo do coeficiente de atenuação foi realizado a partir dos dados de leitura da transmissão ultra-sônica. A penetração ou não da droga foi estudada por análise macroscópica e microscópica. Segundo os resultados obtidos não houve variação significativa nos índices de transmissão e nos coeficientes de atenuação do diclofenaco gel em comparação ao gel neutro. A penetração do medicamento foi de 3 mm para as amostras irradiadas com a intensidade de 1,0 W/\'CM POT.2\' e de 5 mm para as amostras irradiadas com 1,5 W/\'CM POT.2\', não houve evidência de penetração do fármaco no grupo controle. Os resultados obtidos neste estudo sugerem que a fonoforese do diclofenaco gel é efetiva nas intensidades 1,0 e 1,5 W/\'CM POT.2\'. / The objective of the present work was of analyzing, experimentally, the variation of the transmission index and the coefficient of ultrasonic reduction in the half diclofenaco gel, as well as, the penetration of the drug in samples of similar jelly the human skin through the phonophoresis. The variation of these parameters was investigated in 120 agar-agar samples, (continuous way, 1 MHz of frequency, in the intensities of 1,0 and 1,5 W/\'CM POT.2\'), for 5 minutes. The proof bodies form divided in referring groups the ultrasound intensities used, and each one of these groups, it was subdivided in sub-groups corresponding to the different means used for irradiation. The investigation of the ultrasonic transmission was measured starting from a ULTRASONIC POWER METER, model UPM-DT 10. The calculate it of the reduction coefficient was accomplished starting from the data of reading of the ultrasonic transmission. The penetration or not of the drug it was studied for it analyzes macroscopic and microscopic. According to the obtained results there was not significant variation in the transmission indexes and in the coefficients of reduction of the diclofenaco gel in comparison with the neutral gel. The penetration of the medicine went of 3 mm to the samples irradiated with the intensity of 1,0 W/\'CM POT.2\' and of 5 mm for the samples irradiated with 1,5 W/\'CM POT.2\', there was not evidences of penetration of the drug in the group control. The results obtained in this study suggest that the phonophoresis of the diclofenaco gel is effective in the intensities 1,0 and 1,5 W/\'CM POT.2\'.