Transdermal Penetration Enhancers Research Articles

The influence of alcohol, propylene glycol and 1,2-pentanediol on the permeability of hydrophilic model drug through excised pig skin

Alcohol and glycol including 1,2-pentanediol, a new product in this field, were examined for their transdermal penetration enhancing in vitro properties using pig skin and caffeine as a model drug. In order to investigate a possible influence of these compounds, we followed diffusion from an aqueous solution with caffeine followed by a series of different vehicles, their compositions were: (1) in water as a control; (2) in propylene glycol/ethanol/water (25:25:48; v/v/v); (3) in 1,2-pentanediol/water (2.5:95.5, v/v); (4) in 1,2-pentanediol/water (5:93, v/v); in propylene glycol/water (5:93; v/v); and in ethanol/water (5:93; v/v). The stratum corneum/vehicle partition coefficients ( K m), maximum flux ( J), enhancement factor (EF), 24-h receptor concentration ( Q 24h) were determined and compared to control values (caffeine in water). Permeation was also expressed in percentage of the applied dose absorbed in the different compartments. In all test models, caffeine was released and penetrated into pig skin. The 1,2-pentanediol was presented as the most effective enhancer; with a low proportion of this compound (only 5%), caffeine penetrated the skin quicker and in a greater extent. While this compound showed promise as penetration enhancer, further study was required to determine its effectiveness with others drugs and its irritation potential.

An investigation of the interaction of iminosulfurane transdermal penetration enhancers with model skin preparations using NMR spectroscopy

The 31P NMR resonance from the inner and outer leaflets of DMPC in unilamellar vesicle bilayers has been split by use of the slowly penetrating paramagnetic shift reagent, Pr 3+. The perturbing effect of subsequently added iminosulfurane transdermal penetration enhancers (TPEs) is to accelerate the collapse of this splitting, especially in the case of the bromo derivative 3. The aforementioned acceleration of the splitting is enhanced by the addition of 16 mol% cholesterol. Conversely, 33 mol% cholesterol appears to seal the bilayer to the effect of the TPEs—even when present at 20 mol%. These observations are consistent with the deep penetration of the TPEs into the DMPC bilayer, i.e., the perturbation of the bilayer is transmembrane and supports a model in which a subset of the bromo TPE derivative 3 is kinetically trapped in the bilayer. This feature leads to an enhanced residence time of 3 in the bilayer, and by extension to the skin, and therefore to an explanation for the markedly enhanced activity of the bromo TPE derivative relative to that of other halogenated derivatives in the series of iminosulfuranes studied.

Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.

In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.

Penetration-Enhancing Effect of the Essential Oil and Methanolic Extract of Eryngium bungei on Percutaneous Absorption of Piroxicam through Rat Skin

Recently, in order to improve drug permeation through the skin, penetration enhancers have attracted a great deal of interest in increasing percutaneous absorption. Natural compounds like terpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of extract and essential oil of Eryngium bungei (as a traditional anti-inflammatory and antinociceptive) on the transdermal absorption of piroxicam. The stable gel was chosen and enhancing effects of plant extract and essential oil with different concentrations (0.5 - 3.0 and 0.25 - 5.0 % w/w respectively) on the permeation of piroxicam were evaluated. The results showed that the greatest enhancement of the skin transport occurs at the highest concentration of the enhancer (P < 0.01). The most outstanding penetration enhancer was plant essential oil in 5 % w/w, providing an almost 9.17-fold increase in permeability coefficient of piroxicam.

Chronic ethanol ingestion alters xenobiotic absorption through the skin: Potential role of oxidative stress

Alcohol ingestion is correlated with several skin disorders and it has been proposed that changes in skin properties may be an early indicator of alcohol misuse. Topically applied ethanol is an effective transdermal penetration enhancer; however, little is known about the effects of chronic ethanol ingestion on skin. Rats were pair fed a diet containing 36% ethanol for twelve weeks. The animals were then switched to a non-ethanol diet and were monitored for up to four weeks. Non-invasive measurements for changes in dermal blood flow using laser Doppler velocimetry (LDV), damage to skin barrier via transepidermal water loss (TEWL) and changes in skin moisture content were obtained for the experimental duration. At 0, 1 day or 1, 2, 3, 4 weeks after alcohol removal rats were euthanized and their skin was analyzed for alcohol and aldehyde dehydrogenase, and lipid peroxidation. Transdermal penetration of the herbicide paraquat, industrial solvent dimethyl formamide (DMF), insect repellant N,N-diethyl-m-toluamide (DEET) and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was also determined. Transdermal absorption, LDV, TEWL, skin alcohol and aldehyde dehydrogenase, as well as lipid peroxidation significantly increased after continuous ethanol exposure (p<0.05). These factors remain elevated for up to four weeks after termination of ethanol consumption, showing that skin changes induced by alcohol are not immediately reversible and reflect fundamental changes in the skin itself. This work provides a starting point for examining the link between ethanol ingestion and skin disorders associated with alcohol use.

Effect of the Essential Oil of Eryngium caeruleum on Percutaneous Absorption of Piroxicam through Rat Skin

Recently, in order to improve drug permeation trough the skin, penetration enhancers have attracted a great deal of interest in increasing percutaneous absorption. Natural compounds like terpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of different concentrations of essential oil of Eryngium caeruleum on the transdermal absorption of piroxicam. Piroxicam solubility was evaluated and several formulations were developed. The stable gel was chosen and enhancing effects of essential oil with different concentrations (0.25–5.0 % w/w) on the permeation of piroxicam were evaluated using Franz diffusion cells fitted by rat skin. PEG 200: buffer 7.4 (40:60) were used as suitable solvent for selected formulation. The results showed that in all cases (formulations containing plant essential oil) the greatest enhancement of the skin transport occurs at the highest concentration of the enhancer (P < 0.01). There is no direct linear relationship between E. caeruleum essential oil and the permeation rate. The most outstanding penetration enhancer was plant essential oil in 5 % w/w, providing an almost 8.56-fold increase in permeability coefficient of piroxicam. E. caeruleum essential oil have shown ability to enhance the permeation of piroxicam across rat skin. Based on anti-inflammatory and analgesic effects of this genus, and traditional uses, the enhancer effects of E. caeruleum will be emphasized.

Transdermal Penetration Enhancers

Transdermal drug therapy has been one of the major research fields in the area of drug therapy for last few decades. However inspite of its large therapeutic potential market success has been limited. The most important reason being the barrier properties of Stratum Corneum. Various approaches had been tried to breach this barrier .This article briefly reviews the various approaches used to enhance transdermal penetration. Penetration enhancers represent a popular method of increasing drug flux through the skin for local or systemic activity. The article briefly introduces the properties of skin and its barrier characteristics. A classification of various penetration enhancement strategies is given. The following article explores the promise shown by electrical as well as sonicated transdermal drug transport as a novel drug delivery system. The paper details the application of various physical and chemical drugs in transdermal drug delivery. The paper also briefs on use of micro fabricated microneedles and biodegradable enhancers as a novel approach to transdermal drug delivery. The paper concludes with a brief discussion of the future prospects of transdermal penetration enhancers, which can significantly improve the present drug delivery scenario. Keywords: Transdermal penetration enhancers, skin, iontophoresis, electroporation, sonophoresis, microneedles

Moisturizing Lotions can Increase Transdermal Absorption of the Herbicide 2,4-Dichlorophenoxacetic Acid Across Hairless Mouse Skin

Moisturizing lotions can be an effective treatment for occupationally induced dry skin. These compounds are designed to be hygroscopic and retain water to keep the stratum corneum hydrated, while at the same time enhancing the horny layer to prevent increases in transepidermal water loss (TEWL). Skin hydration levels, however, are known to influence barrier properties. The purpose of this work was to compare skin moisture levels induced by four commercially available moisturizing lotions with their capacity as transdermal penetration enhancers using the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) as a model chemical. Further, the effect of moisturizing the skin after washing with sodium lauryl sulfate (SLS) on transdermal absorption was determined. Skin moisture levels were also measured noninvasively and were correlated to penetration enhancement. Hairless mouse skin was pretreated with commercially available moisturizing lotions either with or without SLS washing and in vitro permeability studies were performed with the herbicide 2,4-D. The data demonstrate that pretreatment with three of the four lotions tested increased the transdermal absorption of 2,4-D as evidenced by cumulative penetration or faster lag times (p < 0.05). Skin moisture levels correlated with the penetration enhancement capabilities of the lotion. Washing the skin with 5% SDS increased the transdermal absorption of 2,4-D (p < 0.05) and application of moisturizing lotions increased the absorption further. In summary moisturizing lotions may influence transdermal penetration of the skin, with the more effective moisturizers having a greater effect on 2,4-D absorption.

Transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid is enhanced by both ethanol consumption and sunscreen application

Xenobiotics absorption is a health concern and skin is a major exposure site for many of these chemicals. Both alcohol consumption and topical sunscreen application act as transdermal penetration enhancers for model xenobiotics. The effect of combining these two treatments on transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was therefore examined. Skin from rats ingesting low (1.5 g/kg) medium (4.3 g/kg) or high (6 g/kg) ethanol doses or saline control was treated with a commercially available sunscreen containing titanium dioxide and octyl methoxycinnimate and transdermal absorption of 2,4-D was monitored. Ethanol increased penetration by a factor of 1.9, 2.0 and 2.5 for animals treated with 1.5, 4.3 and 6 g/kg respectively, demonstrating an ethanol-induced dose response. Sunscreen application to skin from ethanol gavaged rats caused 2,4-D absorption above that induced by ethanol alone by an additional factor of 1.3, 2.1 and 2.9 for 1.5, 4.3 and 6 g/kg respectively. Comparing 2,4-D transdermal absorption after exposure to both ethanol and sunscreen with a theoretical value (sum of penetration after ethanol or sunscreen treatment) demonstrates that these two treatments enhance additively at the higher doses tested. Results of this study emphasize the importance of limiting excessive alcohol consumption in individuals with potential herbicide exposure rather than discouraging the use of sunscreens, since the consequences of UV-induced skin cancer are far more series than the risks that would be associated with observed increases in chemical exposure.

The effect of terpene concentrations on the skin penetration of diclofenac sodium

Terpenes and sesquiterpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of terpene concentration on the transdermal absorption of diclofenac sodium from ethanol:glycerin:phosphate buffer solution (60:10:30). Therefore, enhancing effects of various terpenes (menthone, limonenoxide, carvone, nerolidol and farnsol) with different concentrations (0.25, 0.5, 1, 1.5 and 2.5%, v/v) on the permeation of diclofenac sodium were evaluated using Franz diffusion cells fitted with rat skin. Furthermore, solubility of diclofenac sodium in the vehicle in presence of different concentrations of terpenes was determined. The results showed that despite the negligible effect of terpenes on the drug solubility, there was a profound skin penetration enhancement effect, although the terpene enhancers varied in their ability to enhance the flux of diclofenac sodium. The results showed that at the highest concentration of terpene (2.5%, v/v) the rank order of enhancement effect for diclofenac sodium was nerolidol>farnesol>carvone>methone>limonenoxide, whereas at the low concentration of 0.25% the rank order was farnesol>carvone>nerolidol>menthone>limonenoxide. No direct relationship existed between terpene concentration and the permeation rate. The most outstanding penetration enhancer was nerolidol, providing an almost 198-fold increase in permeability coefficient of diclofenac sodium, followed by farnesol with a 78-fold increase.

Synthesis and transdermal penetration-enhancing activity of carbonic and carbamic acid esters—Comparison with transkarbam 12

Transkarbam 12 (T12) is a novel transdermal penetration enhancer with high activity. Its polar head group is formed by carbamic acid salt that is unstable in acidic environment and releases CO 2. To find out whether this property influences its high activity, two series of compounds with CO 2 stronger bound in the polar head have been prepared—carbonic and carbamic acid esters. The carbamate salt in the polar head was found to be essential for the enhancing activity and its decomposition in an acidic environment suggested relating to the mode of action of T12.

Mechanistic studies on percutaneous penetration enhancement by N-(4-halobenzoyl)-S,S-dimethyliminosulfuranes

Halogen-substituted iminosulfuranes are transdermal penetration enhancers (TPEs) in permeation studies using hairless mouse or human cadaver skin. The interaction of N--(4--R-benzoyl)-S,S-dimethyliminosulfuranes 1--4, where R=H, Cl, Br, and I, with l-alpha-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) has been studied using differential scanning calorimetry, isothermal titration calorimetry, nuclear Overhauser effect spectroscopy (NOESY), and NMR spectroscopy, and by calculation of the iminosulfurane polarizabilities in order to elucidate the molecular basis of the TPE activity. The active compounds reduce the melting temperature of the gel-to-liquid-crystal phase transition and induce multiple components in the transition excess heat capacity profile. The partitioning of the bromo derivative 3, the most active compound, into DMPC is unique in that 3 may be trapped in the bilayer, affording an enhanced residence time and a reason for its high TPE activity. The entropy decrease associated with the transfer of 3 to the bilayer is much lower than that for the other compounds, indicating that 3 occupies or induces sites that afford it considerable local motional freedom. Correlations between the iminosulfurane TPE activities, the partition coefficients, and NOESY crosspeak volume were observed. Molecular polarizabilities are not consistent with a TPE mode of action involving interaction of these agents with protein side chains.

Investigation of Iminosulfuranes as Novel Transdermal Penetration Enhancers: Enhancement Activity and Cytotoxicity

Very few chemical enhancers for transdermal drug delivery have been approved for clinical use due to irritancy and toxicity concerns. Novel chemical enhancers (iminosulfuranes) were synthesized and studied for their activity and toxicity. Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone was applied. Samples were taken over 24 h and analyzed by high-performance liquid chromatography. Dermal fibroblasts and epidermal keratinocytes were treated with 0-1.2 M 1-5 for 24 h and cytotoxicity assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] was performed. Furthermore, enhancement activity of 0-0.4 M 2 was studied. Partition coefficient of the model drugs into stratum corneum (SC) was measured and confocal Raman microscopy was used to study the penetration process and possible mechanisms of action of the enhancers. Quantitative structure-activity relationship (QSAR) was analyzed to study the contribution of different intramolecular descriptors to enhancement activity. Iminosulfurane 2 showed the highest enhancement activity. All compounds below 0.2 M were safe to skin cells, and 2 was effective at the concentration of 0.1 and 0.2 M. Mechanisms of action of 2 may include increasing partition coefficient of the model drug into SC and interaction between the enhancer and lipids and protein in the SC. QSAR study indicated contribution of several factors to activity: partition coefficient, hydrogen-bond acceptor, and optimal molecular size. Enhancement activity of 2 was achieved without any cytotoxicity.

Novel transdermal drug penetration enhancer: synthesis and enhancing effect of alkyldisiloxane compounds containing glucopyranosyl group

The syntheses of alkyldisiloxanes containing sugar moiety with various alkyl chain length were investigated, in order to develop a silicone-based transdermal penetration enhancer which was expected to show a low irritation to the skin. 1-Alkyl-3-β-d-glucopyranosyl-1,1,3,3-tetramethyldisiloxanes (Glc–SiCs) were prepared by two-step hydrosilylations of 1-alkene and 1-allyl-β-d-glucose tetraacetate with 1,1,3,3-tetramethyldisiloxane in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect of Glc–SiCs on the percutaneous drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine (ANP) and indomethacin (IND) were used as hydrophilic and hydrophobic model drugs, respectively, and the amount of drug permeating through the rat abdominal skin with or without Glc–SiCs was estimated by HPLC. As a result, Glc–SiCs exhibited a enhancing effect on the permeation of both drugs through the skin, which was influenced by the alkyl chain length of Glc–SiCs. In addition, it was suggested that a suitable balance of polarity would be necessary to appear the high enhancing effect, where Glc–SiCs with octyl and decyl groups exhibited the highest enhancing effect. From the determination of kinetic parameters in the drug permeation, it was also found that this enhancing effect was due to the increase of both partition and diffusion coefficients of drug permeation through the skin. By experiments to determine the amount of cholesterol extracted from the skin, the defatting effect would be one of the functions of Glc–SiCs which resulted in the high enhancing activity. Furthermore, according to the Draize test, it was confirmed that Glc–SiCs showed a low irritation to the skin.

Effect of different terpene-containing essential oils on permeation of estradiol through hairless mouse skin

Purpose of the present investigation was to evaluate six terpene-containing essential oils for their capacity to promote permeation of estradiol (ES) through hairless mouse skin in vitro. Tests on cajuput, cardamom, melissa, myrtle, niaouli and orange oil, all used at the 10% w/w concentration in propylene glycol (PG), evidenced niaouli oil (NIA) as the best permeation promoter for ES. Tests on the main terpene components of NIA (1,8 cineole, α-pinene, α-terpineol and d-limonene), evaluated neat (10% w/w in PG) or in admixture, confirmed the better promoting activity of whole NIA. The present data point to the validity of complex terpene mixtures, such as that composing NIA, as transdermal penetration enhancers for moderately lipophilic drugs like ES.

Polymeric transdermal drug penetration enhancer: The enhancing effect of oligodimethylsiloxane containing a glucopyranosyl end group

Oligodimethylsiloxanes (ODMSs) containing a β- d-glucopyranosyl group at one chain end (Glc–ODMSs) with various molecular weights were prepared to develop a silicone-based polymeric transdermal penetration enhancer with a non-ionic polar end group. Glc–ODMSs were prepared by hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-β- d-glucose tetraacetate in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect in the drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine was used as a model drug, and the amount of drug permeating through the rat abdominal skin with or without Glc–ODMS was determined by HPLC. These enhancers were effective for the penetration of antipyrine. On the other hand, the enhancing effects were influenced by the concentration of Glc–ODMS coexisted regardless of its ODMS chain length. The enhancing effect was also observed by the pretreatment of the skin with Glc–ODMS before the drug permeation, the results of which suggested that the induction periods to appear the enhancing effects were different between Glc–ODMSs with the short and the long ODMS chain lengths. Furthermore, according to the Draize test, Glc–ODMSs exhibited no irritation to the skin regardless of the ODMS chain length.

Drug permeation enhancement via buccal route: possibilities and limitations

Over the last decade, there has been a particular interest in delivering drugs, especially peptides and proteins via the buccal route. It provides direct entry into the systemic circulation thus avoiding the hepatic first-pass effect and degradation in the gastrointestinal tract, ease of administration, and the ability to terminate delivery when required. However membrane permeation can be a limiting factor for many drugs administered via the buccal route, and the epithelium that lines the oral mucosa is a very effective barrier to the absorption of drugs. In order to deliver broader classes of drugs across the buccal mucosa, reversible methods of reducing the barrier potential of this tissue must be employed. This requisite has fostered the study of penetration enhancers that will safely alter the permeability restrictions of the buccal mucosa. It has been shown that buccal penetration can be improved by using various classes of transmucosal and transdermal penetration enhancers such as bile salts, surfactants, fatty acids and derivatives, chelators, cyclodextrins and chitosan. Among these chemicals used for the drug permeation enhancement, bile salts are most common. The first part of this paper focuses on work related to the elucidation of mechanisms of action of bile salts in buccal permeation enhancement of various drugs and mucosal irritation. In the second part, results showing the enhancing effect of chitosan on buccal permeation of hydrocortisone, a commonly used topical oral anti-inflammatory agent, and transforming growth factor beta (TGF-β), which is a bioactive peptide to which the oral mucosa is relatively impermeable is presented.

Preparation of oligodimethylsiloxanes with sugar moiety at a terminal group as a transdermal penetration enhancer

Oligodimethylsiloxanes (ODMSs) containing glucose or cellobiose moiety at a terminal group were prepared to develop a silicone-based transdermal penetration enhancer. Glucopiranosyl-terminated ODMS was prepared by the hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-β-D-glucose tetraacetate followed by hydrolysis of the acetyl groups with sodium methoxide, to afford glucopiranosyl-terminated ODMS with a ether linkage between glucopiranosyl and ODMS components (GlcO-ODMS), and by the coupling reaction of iodopropyl-terminated ODMS with 2-(2,3,4,6-O-tetraacetyl-β-D-glucopyranosyl)thiopseudourea hydrobromide followed by the similar hydrolysis to afford glucopiranosyl-terminated ODMS with a thioether linkage (GlcS-ODMS). Cellobiosyl-terminated ODMS (Cell-ODMS) was also prepared by the similar procedure as GlcO-ODMS. The enhancing activity of GlcO-ODMS, GluS-ODMS and Cell-ODMS on the drug permeation through the rabbit abdominal skin was evaluated by in vitro experiments using a two-chamber diffusion cell and antipyrine as a model drug. The permeation of antipyrine through the skin was increased by the addition of GlcS-ODMS and GlcO-ODMS but not by Cell-ODMS.

Preparation of oligodimethylsiloxanes with sugar moiety at a terminal group as a transdermal penetration enhancer

Oligodimethylsiloxanes (ODMSs) containing glucose or cellobiose moiety at a terminal group were prepared to develop a silicone-based transdermal penetration enhancer. Glucopiranosyl-terminated ODMS was prepared by the hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-β-D-glucose tetraacetate followed by hydrolysis of the acetyl groups with sodium methoxide, to afford glucopiranosyl-terminated ODMS with a ether linkage between glucopiranosyl and ODMS components (GlcO-ODMS), and by the coupling reaction of iodopropyl-terminated ODMS with 2-(2,3,4,6-O-tetraacetyl-β-D-glucopyranosyl)thiopseudourea hydrobromide followed by the similar hydrolysis to afford glucopiranosyl-terminated ODMS with a thioether linkage (GlcS-ODMS). Cellobiosyl-terminated ODMS (Cell-ODMS) was also prepared by the similar procedure as GlcO-ODMS. The enhancing activity of GlcO-ODMS, GluS-ODMS and Cell-ODMS on the drug permeation through the rabbit abdominal skin was evaluated by in vitro experiments using a two-chamber diffusion cell and antipyrine as a model drug. The permeation of antipyrine through the skin was increased by the addition of GlcS-ODMS and GlcO-ODMS but not by Cell-ODMS.

Ionisation and the effect of absorption enhancers on transport of salicylic acid through silastic rubber and human skin

Propose: to investigate if salicylic acid (SA)-permeation through excised human skin (HS) and silastic rubber (SR) conforms to the pH-hypothesis and to assess the influence of a range of absorption enhancers on the transport of SA with and without a transmembrane pH-gradient. Methods: Franz cells were used to study SA permeation from solutions and saturated suspensions. McIlvaine buffers were used to maintain transmembrane pH-gradients. Membrane pretreatment was used to study the action of absorption enhancers. Results: the flux of SA from solutions was dependent upon the vehicle pH and permeant concentration was directly related to the degree of ionisation of the solute. Flux from suspensions was independent of pH, since the level of unionised drug, the predominant diffusing species, was maintained at the intrinsic saturated solubility at all pH values. The observed SA flux enhancement across human skin without a transmembrane pH-gradient was not significantly different from the enhancement with a pH-gradient for all of the absorption enhances used, except for dodecylamine. Conclusions: the results showed that SA permeation conformed to the pH-partition hypothesis. The evidence from absorption-enhancer pretreatment demonstrated that, under certain conditions, the transdermal penetration enhancement of a number of topical enhancing compounds, including Azone and oleic acid can be explained without recourse to ion-pair phenomena.