Vehicles based on a sugar surfactant: Colloidal structure and its impact on in vitro/in vivo hydrocortisone permeation

An emerging class of natural surfactants, named alkylpolyglucosides, which can form both, the thermotropic and the lyotropic liquid crystalline phases, were focused. The aim of the study was to integrate some physicochemical properties (characterised through the polarization and transmission electron microscopy, wide-angle X-ray diffraction, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, with the in vitro (the artificial skin constructs) and in vivo bioavailability of hydrocortisone (HC), in comparison with a standard pharmacopoeial vehicle. The parameters measured in vivo were erythema index (an instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration. A complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type was deduced for sugar surfactant-based vehicles. In dependence on surfactant/water/oil ratio, several thermodinamically variable fractions of water were predicted. Rheological profile of the vehicle appeared to influence the in vitro profile of permeation. A surplus of total amount of drug permeated in vitro from the alkylpolyglucoside-based vehicles coincided with the more pronounced increase of TEWL and less marked blanching action of HC from the selected alkylpolyglucoside-based vehicle tested in vivo, related to the pharmacopoeial one. These findings imply an enhanced delivery of HC from this vehicle and its putative penetration enhancing effect, probably dependent on specific distribution of the vehicle's inherent water.     

Natural surfactant-based topical vehicles for two model drugs: Influence of different lipophilic excipients on in vitro/in vivo skin performance

This study focuses on the properties of topical vehicles based on alkylpolyglucoside natural surfactant-mixed emulsifier, cetearyl glucoside and cetearyl alcohol, in order to propose their use as “ready to use” pharmaceutical bases for a number of model drugs. We were interested to investigate how the alternative use of three lipophilic excipients (Ph. Eur. 6.0), differing in their polarity indexes (medium chain triglycerides (MG), decyl oleate (DO), and isopropyl myristate (IPM), respectively), affects the colloidal structure of the alkylpolyglucoside-based vehicles and in vitro permeation profiles of two model drugs: diclofenac sodium (DC) and caffeine (CF), both sparingly soluble in water. Finally, we aimed to evaluate the safety profile of such vehicles in vitro (acute skin irritation test using a cytotoxicity assay), comparing it with in vivo data obtained by the methods of skin bioengineering.The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. Varying of lipophilic excipient influenced noteworthy variations in the colloidal structure demonstrated as different rheological profiles accompanied to the certain degree by different water distribution modes, but notably provoked by drug nature (an amphiphilic electrolyte drug vs. nonelectrolyte). In vitro permeation data obtained using ASC membranes in an infinite dose-type of experiment stressed the importance of the vehicle/solute interactions in case of small variation in formulation composition, asserting the drug properties in the first hours of permeation and rheological profile of the vehicles in the later phase of experiment as decisive factors. In vitro skin irritation test demonstrated a mild nature of the emulsifying wax and the absence of negative effects of used oil phases on cell viability in formulation concentrations correspondent to the therapeutic need. This result alongside with data obtained from in vivo study, could additionally promote investigated topical vehicles as prospective “ready to use” pharmaceutical bases.     

Topical vehicles based on natural surfactant/fatty alcohols mixed emulsifier: The influence of two polyols on the colloidal structure and in vitro/in vivo skin performance

There is a growing need for in-depth research into new skin- and environment-friendly surfactants, such as alkylpolyglucosides. The aim of this study was to assess whether, to which extent and by what mechanism the two commonly used hydrophilic excipients, propylene glycol (PG) and glycerol (GL), affect the colloidal structure of emulsions formed by a natural mixed emulsifier, cetearyl glucoside and cetearyl alcohol. Furthermore, the study was concerned with the effect of these changes on in vitro permeation profiles of two model drugs (diclofenac sodium and caffeine) and in vivo skin performance of the test samples. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. PG addition produced a stronger hydrophilic lamellar gel phase than GL, which was independent on the model drug used. PG-containing vehicles have revealed a considerable amount of interlamellar PG/water mixture, with incorporated drug. In vitro permeation data obtained using artificial skin constructs (ASC) confirmed the relationship between rheological profiles of vehicles and the extent of skin delivery. Higher permeation profiles of both drugs from PG-containing formulations coincided with a higher increase in transepidermal water loss observed in in vivo study on human volunteers, which confirms the penetration/permeation enhancer effect of PG. It also indicates the existence of the vehicle/ASC interactions analogous to those between the vehicle and the skin, thus affirming the use of ASC as a reliable tool for permeation studies. Contrary to the effect of PG, the results obtained with GL suggest that it may have a permeation-retarding rather than a permeation-enhancing effect in topical vehicles of this type.     

Formulation and evaluation of flurbiprofen microemulsion

The purpose of the present study was to investigate the microemulsion formulations for topical delivery of Flurbiprofen (FP) in order to by pass its gastrointestinal adverse effects. The pseudoternary phase diagrams were developed and various microemulsion formulations were prepared using Isopropyl Myristate (IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant and Sorbitan Monooleate as cosurfactant. The transdermal permeability of flurbiprofen from microemulsions containing IPM and EO as two different oil phases was analyzed using Keshary-Chien diffusion cell through excised rat skin. Flurbiprofen showed higher in vitro permeation from IPM as compared to that of from EO microemulsion. Thus microemulsion containing IPM as oil phase were selected for optimization. The optimization was carried out using 2(3) factorial design. The optimized formula was then subjected to in vivo anti-inflammatory study and the performance of flurbiprofen from optimized formulation was compared with that of gel cream. Flurbiprofen from optimized microemulsion formulation was found to be more effective as compared to gel cream in inhibiting the carrageenan induced rat paw edema at all time intervals. Histopathological investigation of rat skin revealed the safety of microemulsion formulation for topical use. Thus the present study indicates that, microemulsion can be a promising vehicle for the topical delivery of flurbiprofen.     

Transdermal iontophoretic delivery of diclofenac sodium from various polymer formulations: in vitro and in vivo studies

The objective of this study was to evaluate the in vitro and in vivo transdermal iontophoresis of various diclofenac sodium polymer formulations. The excised rat skin, human skin as well as cellulose membrane were used to examine the in vitro drug permeation whereas the microdialysis technique was used to monitor the drug concentration in vivo. Polymer solutions based on polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) binary system showed higher drug permeability than that of single polymer vehicle. The effect of formulations on drug permeation through cellulose membrane was quite different from those through rat skin and human skin, which can be explained by the different permeation pathways between them. It appeared to be a membrane-controlled mechanism but not the vehicle matrix-controlled mechanism for diclofenac hydrogels when using skin as the diffusion barrier. The recovery of diclofenac sodium in the in vivo microdialysis was approximately 80-90%, indicating this technique can be used in the intradermal drug monitoring. For all the polymer formulations tested, there was a good relationship between the in vitro and in vivo drug permeation. A synergistic effect on drug permeation was observed when transdermal iontophoresis combined with the pretreatment of cardamom oil as a permeation enhancer.     

Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE)

A prodrug, temozolomide acid hexyl ester (TMZA-HE), was identified as a skin-deliverable congener for temozolomide (TMZ) to treat skin cancers. Poor solubility and instability of TMZA-HE rendered a serious challenge for formulation of a topical preparation. Microemulsions (ME) were chosen as a potential vehicle for TMZA-HE topical preparations. ME systems were constructed with either oleic acid (OA) or isopropyl myristate (IPM) as the oil phase and tocopheryl (vitamin E) polyethylene glycol 1000 succinate (VE-TPGS) as a surfactant. Topical formulations of OA and IPM ME systems demonstrated beneficial solubilising ability and provided a stable environment for the prodrug, TMZA-HE. Significant differences between the microstructures of OA and IPM ME systems were revealed by freeze fracture electron microscopy (FFEM) and different loading abilities and permeation potencies between the two systems were also identified. In permeation studies, IPM ME systems, with inclusion of isopropyl alcohol (IPA) as a co-surfactant, significantly increased TMZA-HE permeation through silicon membranes and rat skin resulting in less drug retention within the skin, while OA ME systems demonstrated higher solubilising ability and a higher concentration of TMZA-HE retained within the skin. Therefore IPM ME systems are promising for transdermal delivery of TMZA-HE and OA ME systems may be a suitable choice for a topical formulation of TMZA-HE.     

Cremophor RH40-PEG 400 microemulsions as transdermal drug delivery carrier for ketoprofen

The aim of this study was to prepare novel microemulsion for transdermal drug delivery of ketoprofen (KP). The microemulsion composed of ketoprofen as model drug, isopropyl myristate (IPM) as oil phase, surfactant mixture consisting of polyoxyl 40 hydrogenated castor oil (Cremophor RH40) as surfactant and polyethylene glycol 400 (PEG400) as co-surfactant at the ratio 1:1, and water were prepared. The viscosity, droplet size, pH, conductivity of microemulsions, and skin permeation of KP through shed snake skin were evaluated. The particle size, pH, viscosity and conductivity of microemulsions were in the range of 114-210 nm, 6.3-6.8, 124-799 cPs and 1-45 μS/cm, respectively. The ratio of IPM, and surfactant mixture played the important role in the skin permeation of KP microemulsions. As the amount of surfactant mixture and IPM increased, the skin permeation of KP decreased. The formulation composed of 30% IPM, 45% surfactant mixture and 25% water showed the highest skin permeation flux. The incorporation of terpenes in the 2.5% KP microemulsions resulted in significant enhancement in skin permeation of KP. The rank order of enhancement ratio for skin permeation enhancement of terpenes was α-pinene > limonene > menthone. The results suggested that the novel microemulsion system containing IPM, water, Cremophor RH40:PEG400 and terpenes can be applied for using as a transdermal drug delivery carrier.     

Transdermal oxymorphone formulation development and methods for evaluating flux and lag times for two skin permeation-enhancing vehicles

Oxymorphone is a candidate for transdermal delivery since it is a very potent analgesic, is not very effective orally, and has a short duration of action. In developing a transdermal delivery system, two criteria that were considered important were achieving adequate flux and minimizing the lag time. Oxymorphone skin permeation rates in vitro were very low unless skin permeation enhancers were included in the vehicle. After an initial screen of 17 formulations, two skin permeation-enhancing formulations were selected for further study. These were myristic acid:propylene glycol:oxymorphone base (A), and decylmethylsulfoxide:ethanol:water:oxymorphone.HCl (B). With either formulation and either human or hairless guinea pig skin, there was little dependence of either in vitro flux or lag time on the section of skin used (stratum corneum, epidermis, epidermis/dermis). There were significant differences between human skin and hairless guinea pig skin when comparing in vitro fluxes with the two formulations. With formulation A, fluxes through hairless guinea pig skin were three-to fivefold greater than through human skin. With B, however, fluxes through human skin were up to fivefold greater than through hairless guinea pig skin. In vitro lag times with A were generally long (approximately 24 h), whereas those with B were much lower (approximately 1 to 10 h). The species dependence of permeation enhancement and the differences in lag time between formulations could be related to differences in the mechanisms of permeation enhancement. In vivo lag times with the fatty acid:propylene glycol vehicle were estimated in hairless guinea pigs based on plasma oxymorphone concentrations. These were much lower than in vitro lag times.     

Methods for in vitro percutaneous absorption studies III: hydrophobic compounds

The absorption of two hydrophobic compounds through rat skin was measured by in vivo and in vitro techniques. The permeation of the fragrance ingredients 3-phenyl-2-propenyl 2-aminobenzoate (I) and 1-(3-ethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)+ ethanone (II) was measured from a petrolatum and an acetone vehicle. Increases in permeation of 8-fold (I) and 95-fold (II) were observed when the compounds were tested in vivo under conditions similar to in vitro procedures. The apparent inability of the compounds to freely enter the diffusion cell receptor fluid was partially reversed by replacing normal saline with other fluids: rabbit serum, 3% bovine serum albumin, organic solvents, and dilutions of four nonionic surfactants. The effect of the receptor fluids on the integrity of the skin barrier was assessed by measuring the permeability of control compounds (cortisone, urea, and water). A 6% solution of polyethylene glycol 20 oleyl ether was the receptor fluid of choice. Without apparent damage to the skin, 61% (petrolatum vehicle) or 73% (acetone vehicle) of the in vivo absorption of I was obtained. With II, only 32% of the in vivo absorption was achieved (petrolatum vehicle). Even when the surfactant solution is used, significant differences may still remain between in vivo and in vitro results.     

Microemulsion: a novel transdermal delivery system to facilitate skin penetration of indomethacin

In this study, we aimed to develop thermodynamically stable microemulsion formulations of indomethacin with lower surfactant and cosurfactant contents, to improve drug permeability. Formulations were based on the oil/water microemulsion region of pseudo-ternary phase diagrams. The characteristic parameters (viscosity, diameter, and polydispersity) of the microemulsion formulations were then determined. In vitro permeation studies were performed using Franz diffusion cells. Permeation through mouse skin and skin retention of indomethacin microemulsions and ointment were tested. The cumulative amount of permeated indomethacin and its skin retention were significantly higher in microemulsion formulations compared with ointment. Drug flux and skin retention improved with decreasing droplet diameter of the microemulsions. On the basis of these results, we suggest some possible mechanisms for the enhanced transdermal permeation of drugs in microemulsions, including high drug-loading capacity, permeation enhancement by surfactants and cosurfactants, and smaller droplet diameter. In conclusion, microemulsions represent a novel transdermal delivery vehicle for increasing the solubility and permeability of indomethacin.     

Development and evaluation of a monolithic drug-in-adhesive patch for valsartan

The purpose of this study was to investigate the feasibility of a monolithic drug-in-adhesive (DIA) patch as a transdermal therapeutic system for the administration of valsartan (VAL). To improve the penetration of VAL in the patch, several chemical penetration enhancers were investigated by in vitro hairless mouse and Yucatan micro pig (YMP) skin permeation studies. A combination of isopropyl myristate (IPM)/diisooctyl sodium sulfosuccinate (AOT) most strongly enhanced the permeation of VAL. Since the concentration of VAL through the patch in hairless rat (HR) in vivo was correlated with that in HR skin in vitro, VAL that permeated through the skin could effectively pass into the systemic circulation. The plasma concentration-time profile of VAL after the patch was applied in humans was estimated by a convolution technique from the results of the in vitro YMP study, which indicated that the concentration of VAL could be sufficient to produce a pharmacological effect. These results demonstrate that the combination of IPM/AOT may be useful for the development of a practical DIA patch for VAL.     

Liposomes and niosomes as potential carriers for dermal delivery of minoxidil

The aim of this work was to formulate minoxidil loaded liposome and niosome formulations to improve skin drug delivery. Multilamellar liposomes were prepared using soy phosphatidylcholine at different purity degrees (Phospholipon 90, 90% purity, soy lecithin (SL), 75% purity) and cholesterol (Chol), whereas niosomes were made with two different commercial mixtures of alkylpolyglucoside (APG) surfactants (Oramix NS10, Oramix CG110), Chol and dicetylphosphate. Minoxidil skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either drug vesicular systems or propylene glycol-water-ethanol solution (control). Penetration of minoxidil in epidermal and dermal layers was greater with liposomes than with niosomal formulations and the control solution. These differences might be attributed to the smaller size and the greater potential targeting to skin and skin appendages of liposomal carriers, which enhanced globally the skin drug delivery. The greatest skin accumulation was always obtained with non-dialysed vesicular formulations. No permeation of minoxidil through the whole skin thickness was detected in the present study irrespective of the existence of hair follicles. Alcohol-free liposomal formulations would constitute a promising approach for the topical delivery of minoxidil in hair loss treatment.     

Novel dithranol phospholipid microemulsion for topical application: development, characterization and percutaneous absorption studies

The objective of this study was to develop and characterize a novel dithranol-containing phospholipid microemulsion systems for enhanced skin permeation and retention. Based on the solubility of dithranol, the selected oils were isopropyl myristate (IPM) and tocopherol acetate (TA), and the surfactants were Tween 80 (T80) and Tween 20 (T20). The ratios of cosurfactants comprising of phospholipids and ethanol (1?:?10) and surfactant to co-surfactant (1?:?1 and 2.75?:?1) were fixed for the phase diagram construction. Selected microemulsions were evaluated for globule size, zeta potential, viscosity, refractive index, per cent transmittance, stability (freeze thaw and centrifugation), ex vivo skin permeation and retention. The microemulsion systems composed of IPM and T80 with mean particle diameter of 72.8?nm showed maximum skin permeation (82.23%), skin permeation flux (0.281?mg/cm2/h) along with skin retention (8.31%) vis-à-vis systems containing TA and T20. The results suggest that the developed novel lecithinized microemulsion systems have a promising potential for the improved topical delivery of dithranol.     

Transdermal delivery of antiparkinsonian agent, benztropine. I. Effect of vehicles on skin permeation

The influence of pH and various lipophilic and hydrophilic vehicles on the epidermal permeation of benztropine (BZ) free base and its mesylate salt were studied in vitro using the hairless mouse (HLM) and human cadaver (HC) skin membranes. The pH-partition behavior of BZ base (pK(a)=10) was examined using n-octanol and Britton-Robinson buffers over the pH range of 5-12. Unexpectedly, the ionized species of BZ yielded a high partition coefficient (log K(octanol/water)=2. 14), which was reflected by its relatively high skin permeability (P=1.6x10(-2)cm h(-1)). BZ base delivered from a lipophilic vehicle with a solubility parameter range of 7.1-10.3 (cal cm(3))(1/2) exhibited a significantly enhanced rate of permeation as compared to that attained from a hydrophilic vehicle of solubility parameter range between 12.5-23.4 (cal cm(3))(1/2). Among the neat solvents examined, a lipophilic carrier, isopropyl myristate (IPM) provided the most enhancing effect on the permeation of BZ base. In addition, the neat IPM carrier offered the maximum BZ base flux of 150 microg per cm(2) h(-1) across HC skin, which was approximately 16 times greater than the target delivery rate of BZ from a 10-cm(2) device. In comparison, BZ base exhibited a 2-60 times greater flux than BZ mesylate when delivered from the neat solvents. However, interestingly enough, the binary cosolvents consisting of IPM and short-chain alkanols such as ethanol (EtOH), isopropanol (iPrOH), and tertiary butanol (tBtOH), in particular a 2:8 combination, produced a marked synergistic enhancement of BZ flux from the mesylate salt, whereas a retarding effect was noticed for the permeation of BZ base. The enhancement potency for the BZ mesylate permeation increased linearly with the carbon number of the branched alcohols present in the binary mixtures. A tBtOH-IPM (2:8) combination produced the highest BZ flux from the mesylate salt, i.e. , 2016 mg per cm(2) h(-1), which was 100-fold greater than from water and 44-540-fold greater than the individual neat solvents, respectively. The observed permeation enhancement of BZ mesylate by the alkanol-IPM mixtures was probably as a result of a combination of decreasing barrier ability of the stratum corneum by the binary vehicles and moderately partitioning BZ mesylate through the viable epidermis/dermis.     

Effect of phosphatidylcholine on skin permeation of indomethacin from gel prepared with liquid paraffin and hydrogenated phospholipid

The effects of hydrogenated and unhydrogenated phosphatidylcholine (HPC, PC) on the permeation of indomethacin (IM) through hairless rat skin were investigated using liquid paraffin (LP) and a gel prepared with LP and hydrogenated soybean phospholipid (HSL). IM solubility at 95 degrees C increased in proportion to the concentration of HPC or PC, whereas solubility at 37 degrees C did not increase with HPC. IM showed no permeation until 10 h from LP without HPC/PC, but permeated at rates of approximately 5 and 10 microg/cm2 within 10 h from LP with HPC and PC, respectively. The permeation from the gel with various formulations (HSL, 15%; PC/HPC, 0-5%; IM, 0.5-2%) was determined. Permeation rates were 1.7-4.8 microg/cm2 per h and were proportional to the skin concentration. Skin concentration was correlated to the release rate from the gel. We concluded that IM was solubilized by phospholipids, high activity in the vehicle led to high partition of IM in skin, and permeation increased due to a high skin concentration.     

Antipsoriatic microemulsion gel formulations for topical drug delivery of babchi oil (Psoralea corylifolia)

The aim of this study was to investigate and evaluate a microemulsion gel-based system of babchi oil (Psoralea corylifolia) for the treatment of psoriasis, which could provide improved permeation of the drug through the skin and increased patient compliance. Babchi oil is used because its chief constituent psoralen is a photoactive furocoumarin that binds to DNA when exposed to UV light to form photoproducts with pyrimidine base. This action inhibits DNA synthesis and causes decrease in cell proliferation. Moreover, babchi oil, in addition to providing psoralen, also acts as an oily phase for microemulsion system. The presence of surfactant and cosurfactant increases the permeation. On the basis of qualitative and quantitative estimation of all eight brands of babchi oil, Bakuchi Tail was selected for microemulsion formulation. Microemulsions were prepared by aqueous phase-titration method. Pseudoternary phase diagrams were constructed for the identification of microemulsion existence zones. Prepared microemulsions were subjected to different thermodynamic stability tests and characterized for droplet size, viscosity and refractive index. In vitro skin permeation of babchi oil through rat abdominal skin was determined by the Franz diffusion cell. The in vitro skin permeation profile of formulation F2, which consisted of 1.67% v/v of babchi oil, 8.33% v/v of oleic acid, S(mix) 55% v/v of Tween 80 Transcutol-P (S/Co ratio 1:1) and 35% v/v of distilled water, was significant when compared with other microemulsion formulations (p < 0.05). Formulation F2 was converted into microemulsion gel by adding 1% Carbopol-940 and coded as MGF2. Formulation MGF2 was selected for its in vivo antiinflammatory effects determined by footpad edema. The results suggested that microemulsion gel is a potential vehicle for improved topical delivery of psoralen and that microemulsion gels are potential vehicles for improved topical delivery of babchi oil.     

Phospholipid polymer, 2-methacryloyloxyethyl phosphorylcholine and its skin barrier function

The effect of poly[2-methacryloyloxyethyl phosphorylcholine] (pMPC) on the skin permeation property was investigated by performing in vitro skin permeation study of a model drug, nicotinic acid (NA). Effect of pMPC polymer in donor solution on skin permeation rates was evaluated using side-by-side diffusion cells. Also, the structural alterations in the stratum corneum (SC), inter-lamellar bilayer (ILB) and dermis layers in pMPC-treated and -untreated skin sections were investigated with transmission electron microscopy (TEM). The permeation profile of NA without pMPC in donor solution showed biphasic mode: initial 1st phase and 2nd hydration phase. The sudden, more than 10-fold increase in flux from the initial steady state (43.5 microg/cm2/hr) to the 2nd hydration phase (457.3 microg/cm2/h) suggests the disruption of skin barrier function due to extensive hydration. The permeation profile of NA with 3% pMPC in the donor solution showed monophasic pattern: the steady state flux (10.9 microg/cm2/h) without abrupt increase of the flux. The degree of NA permeation rate decreased in a concentration-dependent manner of pMPC. TEM of skin equilibrated with water or 2% pMPC for 12 h showed that corneocytes are still cohesive and epidermis is tightly bound to dermis in 2% pMPC-treated skin, while wider separation between corneocytes and focal dilations in inter-cellular spaces were observed in water-treated skin. This result suggests that pMPC could protect the barrier property of the stratum corneum by preventing the disruption of ILB structure caused by extensive skin hydration during skin permeation study.     

Influence of electrical parameters in the iontophoretic delivery of a small peptide: in vitro studies using arginine-vasopressin as a model peptide

The present investigation was carried out to understand the influence of electrical parameters on iontophoretic transport of a small peptide like arginine-vasopressin (AVP). In vitro studies using rat skin were conducted to assess the effect of different current densities (CDs), durations, duty cycles and alternating polarity on vasopressin permeation. HPLC was used for ensuring electrochemical stability of the peptide whereas FT-IR and TGA were used to understand the biophysical changes caused in skin due to passage of current. Application of CD > 0.75 mA/cm(2) was found to compromise skin barrier integrity as well as electrochemical stability. Periodic current did not show any significant difference in permeation compared to continuous current. Alternating polarity was useful in reducing pH shift however, was less efficient compared to continuous direct current. FT-IR and TGA studies showed that skin hydration increased as a function of CD and duration and all the results could be explained on the basis of increased skin hydration.     

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 130nm in size, and has a zeta potential of 25mV 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.     

The influence of volatile solvents on transport across model membranes and human skin

Simple topical formulations which include volatile components, such as gels or sprays, are appealing from a cosmetic perspective. However, complex formulation effects may result from the use of volatile excipients in topical formulations, particularly when applied at clinically relevant doses (typically less than a few mg cm⁻²). The present investigation aims to study the role of the volatile solvent ethanol (EtOH), in combination with Transcutol P^® (TC), dimethyl isosorbide (DMI) and isopropyl myristate (IPM), on the efficacy of dermal delivery of a model compound (i.e. methyl paraben). The methodology consisted of in vitro diffusion experiments conducted using silicone membranes and human epidermis. Finite dose studies were performed with two types of formulations: saturated solutions of methyl paraben in each vehicle alone and incorporating the volatile solvent in a 50:50 (v/v) proportion. The kinetics of EtOH evaporation from the formulations were also investigated by monitoring the weight loss of the formulation over time. The results showed that the presence of EtOH had little effect on the skin flux of methyl paraben compared with the corresponding saturated solutions. Formulations incorporating the volatile solvent were clearly more efficient, in line with the data obtained with silicone membranes. Furthermore, the permeation of methyl paraben from the saturated EtOH solution in both silicone and skin showed an initial period of relatively fast permeation, after which there was a marked decrease in the permeation rate. This reflected significant ethanol depletion from the formulation (chiefly by evaporation), causing most of the dose of methyl paraben applied to crystallise as a deposited film at the skin surface (observed experimentally and confirmed by mass balance studies), thus decreasing its availability to permeate. Studies of the kinetics of ethanol evaporation from the formulations confirm these findings, demonstrating a very short residence time of the volatile solvent at the surface of the membrane (approx. 6 min). In conclusion, the findings suggest that rapid evaporation of EtOH takes place from the formulations applied at the surface of the skin, leaving a saturated residue of the drug in the vehicle. The presence of EtOH clearly influenced the efficiency of the formulation, underlining the application of volatile components to optimise dermal delivery.