Effect of Fatty Acid Diesters on Permeation of Anti-Inflammatory Drugs Through Rat Skin

Abstract

Four fatty acid diesters (diethyl succinate, diethyl adipate, diethyl sebacate, and diisopropyl adipate) were used to study their enhancement effect on the permeation of four non-steroidal anti-inflammatory drugs (NSAIDs: ketoprofen, indomethacin, diclofenac sodium, and ibuprofen) through rat abdominal skin. With the diester pretreatment, drug permeation increased and the lag times decreased. No relationship was observed between the solubilities of the drugs in the diesters and the diester enhancement effects. The enhancement effect decreased with an increase of the drug lipophilicity, but increased with an increase of the lipophilic index of the diester up to about 3.5, after which the enhancement effect decreased or remained constant. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to investigate the biophysical changes in the stratum corneum lipids caused by the diesters. The FTIR results showed that treatment of the skin with diesters did not produce a blue shift in the asymmetric and symmetric C-H stretching peak positions. However, all of the above diesters showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with water treatment. These results suggested that the diesters were more effective for enhancing the penetration of hydrophilic drugs than lipophilic drugs, and the enhancing effect of lipophilic diesters was more effective than that of hydrophilic diesters. The enhancement effects of diesters may be due to their causing lipid extraction in the skin.

Effect of Esters on the Permeation of Chemicals with Different Polarities through Synthetic Artificial Membranes Using a High-Throughput Diffusion Cell Array

“…It has previously been reported that isopropyl myristate has a fluidizing effect on the intercellular lipids of the stratum corneum 30) and that diethyl sebacate can be used to extract lipids, 17) indicating that both of these esters serve as transdermal absorption enhancers. It has also been found that ketoprofen exhibited increased permeation through hairless rat skin when it was dissolved in low MW esters, 16) and the permeability of stearyl glycyrrhetinate through Yucatan micropig skin with a finite dose was affected by the surface tension and MW of the vehicle.…”

“…The effect of fatty acid esters on the skin permeation of indomethacin and ketoprofen and the effect of diesters on the skin permeation of non-steroidal anti-inflammatory drugs has been reported. [15][16][17] In addition, previous studies found that the permeability of haloperidol was affected by the wettability and surface tension of the formulation.18) Furthermore, the penetration of stearyl glycyrrhetinate through Yucatan micropig skin at a finite dose was affected by the molecular weight and surface tension of the vehicles, 19) and skin permeation of model compounds through porcine skin was affected by the viscosities of the vehicles. 20) These physical properties could be a key parameter to enhance the skin permeation of chemicals.…”

“…The effect of fatty acid esters on the skin permeation of indomethacin and ketoprofen and the effect of diesters on the skin permeation of non-steroidal anti-inflammatory drugs has been reported. [15][16][17] In addition, previous studies found that the permeability of haloperidol was affected by the wettability and surface tension of the formulation.…”

Detection of Long Alkyl Esters of Succinic and Maleic Acid Using TLC-MALDI-MS

“…Recently, many reviews have shown that fermentative production of succinic acid can be more cost-effective than petroleumbased production schemes. [1][2][3] This type of "green" technology is becoming more popular as a means of decreasing pollution caused by many petrochemical processes. Dialkyl esters of succinic acid are widely used in detergents, cosmetics, pharmaceuticals, and processed foods.…”

“…Dialkyl esters of succinic acid are widely used in detergents, cosmetics, pharmaceuticals, and processed foods. [1][2][3] For example, dialkyl ester derivatives of diacids including succinic acid make excellent lubricants and can enhance the quality of diesel fuel when used as additives. [4][5][6] Similar approaches using fatty acid derivatives, commonly known as biodiesel, have recently been reported.…”