Skin Permeation Profiles Research Articles

Electrospinning of Ibuprofen-Loaded Composite Nanofibers for Improving the Performances of Transdermal Patches

The main aim of the present study was to electrospin ibuprofen (IBU)-loaded composite nanofibers to improve the performances of transdermal patches. Cellulose acetate/poly(vinyl pyrrolidone) (CA/PVP) blends were used to fabricate uniform nanofibers. Investigations on the physicochemical properties of CA/PVP solutions indicated that the addition of appropriate PVP improved the electrospinnability of original CA solutions. Detections on the physical states of IBU in medicated CA/PVP nanofibers suggested that IBU was uniformly distributed in nanofibers in an amorphous state. Comparing to IBU-loaded casting membrane, the medicated CA/PVP nanofibers provided a faster IBU diffusion manner and a better ex vitro skin permeation profile due to their high superficial areas and the amorphous IBU. Furthermore, CA/PVP nanofibers exhibited a high water vapor permeability, which could render an improved breathability to transdermal patches. In sum, the electrospun drug-loaded CA/PVP nanofibers exhibited great potentials to improve the thermodynamic stability and breathability of transdermal patches, which could be used to develop new types of transdermal drug delivery system (TDDS).

Nanoemulsion-based gel formulations of COX-2 inhibitors for enhanced efficacy in inflammatory conditions

In the present study, we have investigated the potential of a nanoemulsion (thermodynamically stable transparent dispersions of oil and water having a droplet size <200 nm) formulation for the topical delivery of COX-2 inhibitors using etoricoxib as a model drug. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudo-ternary phase diagrams. The prepared nanoemulsions were subjected to thermodynamic stability testing. Those that passed these tests were characterized for viscosity, droplet size and differential scanning calorimetry. Topical permeation of etoricoxib through porcine abdominal skin was estimated using the Franz diffusion cell. The ex vivo skin permeation profile of optimized formulations was compared with that of etoricoxib conventional gel. A significant increase in permeability was observed in optimized nanoemulsion formulations consisting of 2 % w/w of etoricoxib, 20 % w/w of Triacetin, 38 % w/w of a surfactant mixture (Cremophor RH 40:Transcutol P), and 42 % w/w of water. The anti-inflammatory effects of this formulation on carrageenan-induced paw edema in rats showed a significant increase in the percent inhibition value (84.61 % with the nanoemulsion gel and 92.30 % with the nanoemulsion) as compared with the conventional gel (69.23 %) after 6 h when compared with etoricoxib conventional gel. These results suggest that nanoemulsions can serve as potential vehicles for improved transdermal delivery of anti-inflammatory agents such as etoricoxib.

Topical delivery of aceclofenac as nanoemulsion comprising excipients having optimum emulsification capabilities: preparation, characterization and in vivo evaluation

Objective: The aim of the present study was to investigate the potential of a nanoemulsion for topical delivery of aceclofenac using different excipients having optimum emulsifying ability rather than their solubilizing capacity.Methods: The oil-in-water nanoemulsions were prepared by screening the excipients from the nanoemulsion region of pseudoternary phase diagram. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for viscosity, droplet size, transmission electron microscopy, refractive index and in vitro skin permeation. The in vitro skin permeation profile of optimized nanoemulsion formulation (NE31, containing 23.85% Polyoxy-35-castor oil, 7.95% PEG 400 and 13.6% Triacetin) was compared with that of nanoemulsion gel (NG31) and marketed gel formulation (HIFENAC GEL (HIG)). In vivo anti-inflammatory efficacy studies were also carried out for NE31, NG31 and HIG.Results: The significant (p < 0.001) increase in in vitro permeability and in vivo anti-inflammatory efficacy of the NG31 formulation was observed as compared with HIG formulation.Conclusion: It can be concluded that the selection of surfactant and cosurfactant on the basis of their emulsification capabilities other than the solubilizing capacity of drug is an important criterion for the formulation of nanoemulsion.

Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: The influence of skin recovery on drug absorption

While laser skin resurfacing is expected to result in reduced barrier function and increased risk of drug absorption, the extent of the increment has not yet been systematically investigated. We aimed to establish the skin permeation profiles of tetracycline and sunscreens after exposure to the erbium:yttrium-aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and histopathological examinations were carried out for 5 days after laser treatment on nude mice. Percutaneous absorption of the permeants was determined by an in vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10μm, 2.5J/cm2) to approach the epidermis (25μm, 6.25J/cm2) and upper dermis (40μm, 10J/cm2). Reepithelialization evaluated by transepidermal water loss was complete within 2–4 days and depended on the ablation depth. Epidermal hyperplasia was observed in the 40-μm-treated group. The laser was sufficient to disrupt the skin barrier and allow the transport of the permeants into and across the skin. The laser fluence was found to play an important role in modulating skin absorption. A 25-μm ablation depth increased tetracycline flux 84-fold. A much smaller enhancement (3.3-fold) was detected for tetracycline accumulation within the skin. The laser with different fluences produced enhancement of oxybenzone skin deposition of 3.4–6.4-fold relative to the untreated group. No penetration across the skin was shown regardless of whether titanium dioxide was applied to intact or laser-treated skin. However, laser resurfacing increased the skin deposition of titanium dioxide from 46 to 109–188ng/g. Tetracycline absorption had recovered to the level of intact skin after 5 days, while more time was required for oxybenzone absorption. The in vivo skin accumulation and plasma concentration revealed that the laser could increase tetracycline absorption 2–3-fold. The experimental results indicated that clinicians should be cautious when determining the dose for postoperative treatment.

A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: Characterization and in vitro/in vivo evaluation

This study describes a novel carrier, transethosome, for enhanced skin delivery of voriconazole. Transethosomes (TELs) are composed of phospholipid, ethanol, water and edge activator (surfactants) or permeation enhancer (oleic acid). Characterization of the TELs was based on results from recovery, particle size, transmission electron microscopy (TEM), zeta potential and elasticity studies. In addition, skin permeation profile was obtained using static vertical diffusion Franz cells and hairless mouse skin treated with TELs containing 0.3% (w/w) voriconazole, and compared with those of ethosomes (ELs), deformable liposomes (DLs), conventional liposomes (CLs) and control (polyethylene glycol, PG) solutions. The recovery of the studied vesicles was above 90% in all vesicles, as all of them contained ethanol (7–30%). There was no significant difference in the particles size of all vesicles. The TEM study revealed that the TELs were in irregular spherical shape, implying higher fluidity due to perturbed lipid bilayer compared to that of other vesicles which were of spherical shape. The zeta potential of vesicles containing sodium taurocholate or oleic acid showed higher negative value compared to other vesicles. The elasticities of ELs and TELs were much higher than that of CLs and DLs. Moreover, TELs dramatically enhanced the skin permeation of voriconazole compared to the control and other vesicles (p<0.05). Moreover, the TELs enhanced both in vitro and in vivo skin deposition of voriconazole in the dermis/epidermis region compared to DLs, CLs and control. Therefore, based on the current study, the novel carrier TELs could serve as an effective dermal delivery for voriconazole.

Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ), with minimum surfactant and cosurfactant (Smix) concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2) was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss) and permeability coefficient (Kp) was observed in the optimized nanoemulsion formulation (NE2), which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG), 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2) or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.

Enhanced delivery of cosmeceuticals by microdermabrasion

Microdermabrasion (MDA) is one of the top five nonsurgical cosmetic procedures performed. It is a well-established technology with widespread applications in the cosmetic industry. To investigate the effects of MDA on skin and delivery of cosmeceuticals. The alternation of skin structure post-MDA was examined by histological sectioning and transepidermal water loss measurements. The effect of MDA treatment on skin permeation profiles of hydrophilic and lipophilic molecules was investigated by laser scanning confocal microscopy and in vitro permeation studies. Confocal images indicated different absorption profiles and permeation depths for hydrophilic and lipophilic molecules. Microdermabrasion enhanced the transdermal delivery of nicotinamide, the model hydrophilic compound employed. On the other hand, permeation of retinol, the model lipophilic compound, did not improve after treatment with MDA. When treated with 20 passes, the skin recovered from MDA induced changes in 4 days. Permeation of cosmeceuticals into skin was found to be affected by their lipophilicity. Application of skin care products post-MDA therapy may be promising to improve their dermal uptake.

Temperature and pH Stability Profiles of ortho and para DEET

ABSTRACT − DEET, N,N’-diethyl-m-toluamide, is the most commonly used mosquito repellent. However, it can easilypermeate through skin leading to toxic effects. A recent study showed that the ortho analogue of DEET showed enhancedrepellency with reduced permeation compared to the commercially used meta analogue. Thus, in order to understand thedifferences in properties and effectiveness among the m-, o- and p-analogues of DEET, an HPLC-UV method was developedfor separately analyzing the three analogues. Moreover, stability profiles at temperatures ranging from 30 o C to 70C as wellas pH ranging from pH 3 to pH 9 have been determined. All three analogues were stable with no degradation observed dur-ing the 5 day period. o-DEET therefore could be further developed into a safer and more effective mosquito repellent.Key words − DEET, Temperature stability, pH stability, Mosquito repellency m-DEET is known as the golden standard of mosquito repel-lents for being highly effective, stable and relatively safe (Katzet al., 2008). In most cases it is directly applied to the humanskin protecting against tick-borne diseases (Jensennius et al.,2005) and mosquito-mediated diseases including dengue fever,West Nile virus and Eastern Equine Encephalitis (Gubler,2001). However, information about the mechanism of action ofDEET is still controversial. Studies report that DEET mayblock behavior of mosquitoes by inhibiting chemo-receptorson the mosquito antennae that are stimulated by lactic acid(Dogan et al., 1999) whereas other studies refute this phe-nomenon (Syed and Leal, 2008). Nevertheless, m-DEETexhibits mosquito repellency as shown in the complete pro-tection time (CPT) ranging from 203 to 756 minutes, varyingwith factors including climatic effects, mosquito species andphysical activities (Barnard and Xue, 2004; Bidlingmayer,1994; Bernier et al., 2000).The search for safer and more effective repellents continuesto progress, however, due to the toxicities reported of DEET(Schofield et al., 2007). Possible substitutes to DEET that havebeen reported so far include synthetically prepared Picaridin,IR3535 and Permethrin or lemon eucalyptus or citronellawhich are natural products (Katz et al., 2008). Unfortunately,none of these alternatives seem to exhibit properties that couldbe more advantageous to the current DEET products.Current research for developing repellents make use of sys-tematic bioassays or computer based tools which include aQSAR study of N-acyl-piperidines (Katritzky et al., 2008) anda genetic trial of odorant-binding protein manipulation (Li etal., 2008). One of the shortcomings of the mosquito repellentinvestigation is the use of human subjects or living vertebratesin the bioassays (Dogan et al., 1999). However, recently, anefficient in vitro bioassay system has been established whereblood substitute and collagen membrane were used instead ofhuman blood and skin (Jahn et. al., 2010). The artificial bloodsubstitute was a slight modification of that used by Kogan foran in vitro feeding assay for maintenance of mosquito colonies(Corazza et al., 2005). Unlike Kogan who utilized stretchedparafilm as a skin substitute, Jahn made use of a collagen typemembrane (Ditzen et al., 2008) since the parafilm alone couldnot mimic the physiological skin sufficiently. Moreover, inJahn’s study, skin permeation profiles of DEET and its ana-logues were examined in correlation to the mosquito repel-lency, expressed as CPT. Among the DEET analogues tested,compared to the commercially used meta DEET analogue,ortho DEET revealed enhanced repellency with reduced skinpermeation rate, implying that toxicity due to skin penetrationwould be lessened (Jahn et al., 2010).To estimate the applicability of the ortho DEET analogue, aseparation method for the three DEET isomers needed to beestablished. Because of the similar physicochemical charac-teristics of the three isomers as revealed in the capacity factors

Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent

Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon–carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.

Influence of penetration enhancers on in vitro transdermal permeation of L-tethrahydropalmatine

To study the effect of different penetration enhancers on the in vitro transdermal permeation of 1-tethrahydropalmatine (L-THP) through rat skin. Both natural and chemical synthesis penetration enhancers were applied singly or jointly to investigate the skin permeation rates of l-THP. The skin permeation profiles were evaluated by Valian-Chien permeation cells with isolated rat skin. HPLC-UV method was established to determine the concentration of l-THP in samples. As chemical synthesis penetration enhancer was used alone, 8% azone was observed to be the optimal penetration enhancer with the maximal penetration rate of 21.153 microg x cm(-20 x h(-1). Although 2% menthol crystal or 5% eucalyptus oil was effective as a natural penetration enhancer when used alone, the average penetration rate reached only half of that of 8% azone. The penetration potency of either menthol oil or menthol crystal combined with 8% azone was more effective than that of azone alone (P < 0.05). Either menthol oil or menthol crystal combined with 8% azone is effective on transdermal penetration of l-THP in vitro. There is significant synergistic effect when natural penetration enhancers combined with chemical synthesis penetration enhancers.

Novel Biomaterial for Transdermal Application: In vitro and In vivo Characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76 ± 1.52 ng/mL in 6 h and sustained the release of the drug till 24 h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.

Formulation study of topically applied O/W lotion containing vitamin D3 derivative, focusing on skin permeability of the drug

Permeation of 22-oxacalcitriol-1α, 25-dihydroxyvitamin D3 (OCT) through excited hairless mouse skin was determined after application of OCT as solutions and O/W lotions consisted of different polarities of solvents: medium-chain fatty acid triglyceride (MCT), myristate isopropyl (IPM), 1,3-butylene glycol (1,3-BG), and propylene glycol (PG). OCT concentration in skin was also followed after applying these formulations. A two-layer diffusion model was composed to analyze dermatopharmacokinetic profiles of OCT for each vehicle. In the OCT solutions, skin permeation profile of OCT differed depending on solvent polarity. The O/W lotion with a high MCT content led to a low amount of OCT in skin. On the other hand, the O/W lotion with a high 1,3-BG content led to a high amount of OCT in skin. This dermatopharmacokinetic analysis indicated that addition of MCT to the formulation decreases the skin/vehicle partition coefficient of OCT and increases the diffusion coefficient of OCT in skin. However, the opposite effects on these two parameters were found in the case of 1,3-BG. Thus, skin permeability of OCT differed depending on the solvents used in the formulation. These results indicate that skin permeability of OCT is influenced by the physicochemical properties (i.e. polarity) of OCT, solvent, and skin. Our findings on the solvent effects of the skin permeability of OCT are thus useful for designing topical drug formulation, especially in aiming for bioequivalent dosage formulas.

Vehicle effects on in vitro release and skin permeation of octylmethoxycinnamate from microemulsions

The high content of surfactants is one of the major limits to microemulsions (MEs) use in pharmaceutical and cosmetic field. In this work MEs with low surfactant content were prepared by the phase inversion temperature (PIT) method using different oil phases and emulsifiers. The effects of vehicle composition on in vitro release and skin permeation of octylmethoxycinnamte (OMC), one of the most used UVB filter, was evaluated. These MEs showed droplet sizes in the range 32–77 nm and a single peak in size distribution. MEs prepared using the most lipophilic lipids (decyl oleate or cetyl stearyl isononanoate) showed the lowest stability. In vitro release and skin permeation profiles were affected by both lipophilicty and structure of the lipid used as internal phase and the formulation that released the lowest amount of OMC provided the lowest active compound skin permeation. It is noteworthy that no OMC release and skin permeation were observed using oleth-20/glyceryl oleate as emulsifiers. Furthermore, a skin permeation enhancement effect was observed depending on the vehicle components. The results of this work suggest that PIT MEs could provide controlled skin drug delivery by choosing proper associations of oil phase lipids and emulsifiers.

Pep-1 peptide-conjugated elastic liposomal formulation of taxifolin glycoside for the treatment of atopic dermatitis in NC/Nga mice

In order to develop topical preparations of taxifolin glycoside (TXG) for the treatment of atopic dermatitis (AD), formulations of Pep-1 peptide-conjugated elastic liposomes (Pep1-EL) were examined for their in vitro skin permeation profile and in vivo therapeutic efficacy. TXG-loaded Pep1-EL – a nanovesicle consisting of phosphatidylcholine, Tween 80, N-[4-(p-maleimidophenyl)butyryl]-phosphatidylethanolamine (MPB-PE), and Pep-1 peptide – is 130 nm in size, and has a zeta potential of 25 mV and a deformability index value of 60. Here, we examined the skin permeability of several topical preparations using a Franz diffusion cell mounted with depilated mouse skin and found that formulations of Pep1-EL exhibited superior absorption when compared to aqueous solution, EL or Pep-1 peptide-admixed EL formulations. Both transepidermal water loss and skin surface hydration were also measured using AD-induced NC/Nga mice, and the TXG-loaded Pep1-EL treatment group displayed a significantly expedited recovery in skin barrier function when compared to the controls treated with a TXG aqueous solution ( p < 0.05). AD-associated immune responses – including serum interleukine-4, immunoglobulin E, and interferon-gamma – were also regulated by topical application of TXG-loaded Pep1-EL. In conclusion, the novel Pep1-EL formulation of TXG shows substantial promise in the treatment of AD as a result of its desirable skin delivery-promoting capability.

Inhibition of crystallization in drug-in-adhesive-type transdermal patches

In this study the ability of various additives to inhibit crystallization of two model drugs, captopril and levonorgestrel, in acrylate and silicone adhesives was investigated. Among the various additives tested, PVP was found to be the most effective in inhibiting the crystallization of both drugs. Incorporation of PVP in patches (PVP stabilized patches) allowed incorporation of both drugs in amounts higher than their respective saturation solubility in pure adhesives (saturated patches). Skin permeation profiles of the drugs from the patches across hairless rat skin were obtained using Franz diffusion cells. For the hydrophilic drug captopril the skin flux over the first 24 h was the same for the saturated and PVP stabilized patches, but after 24 h the PVP stabilized patches produced higher skin flux values. However this may be because the saturated patch was depleted of the drug after 24 h. It is not clear if PVP performs as a solubilizer or a crystallization inhibitor for hydrophilic drugs. For the lipophilic drug levonorgestrel, the skin flux profile from the saturated and PVP stabilized patches was the same, suggesting that PVP acts just as a drug solubilizer and does not produce supersaturation.

Transdermal patches for site-specific delivery of anastrozole: In vitro and local tissue disposition evaluation

Anastrozole is a potent aromatase inhibitor and there is a need for an alternative to the oral method of administration to target cancer tissues. The purpose of the current study was to prepare a drug-in-adhesive transdermal patch for anastrozole and evaluate this for the site-specific delivery of anastrozole. Different adhesive matrixes, permeation enhancers and amounts of anastrozole were investigated for promoting the passage of anastrozole through the skin of rats in vitro. The best in vitro skin permeation profile was obtained with the formulation containing DURO-TAK ® 87-4098, IPM 8% and anastrozole 8%. For local tissue disposition studies, the anastrozole patch was applied to mouse abdominal skin, and blood, skin, and muscle samples were taken at different times after removing the residual adhesive from the skin. High accumulation of the drug in the skin and muscle tissue beneath the patch application site was observed in mice compared with that after oral administration. These findings show that anastrozole transdermal patches are an appropriate delivery system for application to the breast tumor region for site-specific drug delivery to obtain a high local drug concentration.

A bioassay for mosquito repellency against Aedes aegypti: method validation and bioactivities of DEET analogues

Vector-borne diseases are still a major mortality factor in Africa and South-east Asia and effective mosquito repellents are therefore needed. An efficient and safe in-vitro assay system using artificial blood and skin substitute could facilitate the development of novel repellents, as most assays currently rely on human subjects or vertebrate whole blood. Moreover, examining the skin permeation profiles could provide safer mosquito repellents. The new assay system could serve as an initial system for testing new repellent candidates upon validation with DEET and its analogues. N,N-Diethyl-meta-toluamide (DEET) and five analogues were synthesised and used to validate a novel in-vitro bioassay using artificial blood and collagen membrane. Repellency against Aedes aegypti was correlated with lipophilicity and skin permeation. The new in-vitro assay showed good reproducibility (interday relative standard deviation <10% at high concentrations). Four of the five DEET analogues showed repellency similar or superior to that of DEET. Repellency correlated linearly with lipophilicity but stronger repellents tended to permeate skin better. The new in-vitro assay using blood substitute and collagen membrane significantly simplifies screening of possible mosquito repellents. Lipophilicity as well as skin permeation profiles should be considered before testing of compounds that are candidates for mosquito repellents.

Comparative Study of Skin Permeation Profiles between Brand and Generic Tulobuterol Patches

Tulobuterol patches are long-acting bronchodilators for percutaneous absorption including the β(2)-adrenoreceptor agonist tulobuterol, as a main ingredient, used for long-term management of pediatric asthma. Since patients who have pediatric asthma often also have atopic dermatitis in which the skin barrier is impaired, we compared the skin penetration profiles of the brand and generic patches using a skin barrier-impaired rat model. Skin penetration was significantly (p<0.001) higher in the generic patches compared with the brand patch, suggesting that it is important to understand the pharmaceutical properties of available products by giving careful consideration not only to the patient's asthma control but also to their skin condition before using tulobuterol patches.

The Molecular Effects of Aloe-Emodin (AE)/Liposome-AE on Human Nonmelanoma Skin Cancer Cells and Skin Permeation

In this study, aloe-emodin (AE) was less cytotoxic to human noncancerous skin cells (premalignant keratinocytic HaCaT and fibroblast Hs68) than to nonmelanoma cancer cells (epidermoid carcinoma A431 and head and neck squamous cell carcinoma SCC25). Notably, AE induced apoptosis by up-regulating tumor necrosis factor-alpha and Fas ligand and their cognate receptors, downstream adaptor TNF-R1-associated death domain and Fas-associated death domain, and activated caspase-8 in A431 and SCC25 cells. Moreover, AE up-regulated p53, increased intracellular reactive oxygen species levels, depleted intracellular-reduced GSH, up-regulated cytochrome c and Bax, down-regulated Bcl-2, and activated caspase-9 and -3. The combinatory use of AE and 5-fluorouracil (5-Fu) achieved significantly more cell death in A431 and SCC25 cells than only the use of AE or 5-Fu, likely via regulation of caspase-8, -9, and -3 expressions. Incorporating AE into the liposomal formulation accelerated cell death of A431 and SCC25 cells within a short time. Furthermore, skin permeation profiles of drug suggest that the liposomal formulation enhances transdermal delivery of AE. Experimental data demonstrate the feasibility of applying liposome to deliver AE in clinical therapy.

Effect of drug chirality on the skin permeability of ibuprofen

The in vitro passive diffusion of S-ibuprofen ( S-IB) and RS-ibuprofen ( RS-IB) through human epidermis was determined to study the effects of drug chirality. S-IB has a lower melting point ( T m = 54 °C) than RS-IB ( T m = 77 °C) and, therefore, a greater solubility ( S-IB: 127 ± 1 μg/mL; RS-IB: 81 ± 1 μg/mL). Supersaturated plasters were prepared by using a poly(dimethylsiloxane) adhesive and Eugragit ® RL and propylene glycol as antinucleant agents. The in vitro skin permeation profiles were determined by Franz cells and human epidermis obtained from three different donors. The permeation profiles of S-IB from saturated solutions resulted statistically higher than those of RS-IB ( p < 0.002). When plasters were used, no differences were noticeable between the enantiomer and racemate ( p > 0.17). The latter unexpected results could be explained considering that the RS-IB or S-IB in vitro release rate constants, determined using 3% w/w or 6% w/w loaded plasters, were not statistically different, suggesting that the drug diffusivity within the adhesive matrix represented the rate limiting step to the skin absorption.