In vitro Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity

Abstract

Abstract. Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a constant driving force with maximum thermodynamic activity. The permeability coefficient (K p ), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10-12 are more effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity, which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%. In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety of penetration enhancers is a prime consideration.

Skin penetration and deposition of carboxyfluorescein and temoporfin from different lipid vesicular systems: In vitro study with finite and infinite dosage application

“…It is proposed that the hydration effect of them on the stratum corneum could make the penetration of hydrophilic drugs easier. However, for the high lipophilic compounds (log P o/w > 2), partition into the "hydrated" stratum corneum are made difficult, consequently, which results in a reduction in their permeation capacity through the skin (Zhang et al, 2010). Another possible reason could be the different molecular mechanisms by which the diffusion through the stratum corneum of CF and mTHPC happens, which has already been discussed above.…”

“…Temoporfin (mTHPC), which is highly lipophilic, is expected to penetrate the skin by non-polar pathways, whereas CF, which is hydrophilic, should utilize the polar pathways. The intrinsic permeability of both hydrophilic and lipophilic penetrants is governed by the composition of the skin, with the former limited by their partitioning into the lipophilic SC and the latter, by partitioning from the SC into the less lipophilic epidermis (Nicoli et al, 2008;Zhang et al, 2010). Consequently, the log P o/w value of drug molecule has an effect on the enhancement efficacy of penetration enhancers.…”

“…Consequently, the log P o/w value of drug molecule has an effect on the enhancement efficacy of penetration enhancers. Hydrophilic molecules such as CF, owing to their low partition coefficient and high hydrogen-bonding potential, would show a dramatic increase in permeation with suitable enhancers, however, lipophilic molecules which move with relative ease through the SC do not have the same opportunity to act as indicators of enhancement (Barry and Bennett, 1987;Verma and Fahr, 2004;Zhang et al, 2010).…”

Penetration effect of Ostrich Oil as a Promising Vehicle on Transdermal Delivery of Sinomenine

“…The physicochemical properties of the permeants, the molecular weight, solubility and log P o/w of drugs, are thought to play an important role in determining the promoting activity of penetration enhancers on the permeation of the drug across the skin 3,15 . In this study, the molecular weight of sinomenine is 329.38 g/mol Table 1 , which is in the relatively range of 200-500 g/mol.…”

“…9-octadecenoic acid 40.7 0.3 was the principal unsaturated fatty acid, followed by 9, 12-octadecadience acid 7.38 0.02 and 9-hexadecenoic acid 7.13 0. 15 . Hexadecanoic acid 32.5 0.3 was the predominant saturated fatty acid, followed by octadecanoic acid 7.43 0.05 .…”