Enhancing and sustaining the topical ocular delivery of fluconazole using chitosan solution and poloxamer/chitosan in situ forming gel

Fungal keratitis is a serious disease that can lead to loss of vision. Unfortunately, current therapeutic options often result in poor bioavailability of antifungal agents due to protective mechanisms of the eye. The aim of this work was to evaluate the potential of a chitosan solution as well as an in situ gel-forming system comprised of poloxamer/chitosan as vehicles for enhanced corneal permeation and sustained release of fluconazole (FLU). For this, in vitro release and ex vivo corneal permeation experiments were carried out as a function of chitosan concentration from formulation containing the chitosan alone and combined with the thermosensitive polymer, poloxamer. Microdialysis was employed in a rabbit model to evaluate the in vivo performance of the formulations. The in vitro release studies showed the sustained release of FLU from the poloxamer/chitosan formulation. Ex vivo permeation studies across porcine cornea demonstrated that the formulations studied have a permeation-enhancing effect that is independent of chitosan concentration in the range from 0.5 to 1.5% w/w. The chitosan solutions alone showed the greatest ex vivo drug permeation; however, the poloxamer/chitosan formulation presented similar in vivo performance than the chitosan solution at 1.0%; both formulations showed sustained release and about 3.5-fold greater total amount of FLU permeated when compared to simple aqueous solutions of the drug. In conclusion, it was demonstrated that both the in situ gelling formulation evaluated and the chitosan solution are viable alternatives to enhance ocular bioavailability in the treatment of fungal keratitis.     

Topical delivery of fluorescence (6‐Cf) labeled and radiolabeled (99m‐Tc) cisplatin and imiquimod by a dual drug delivery system

The present investigation deals with the development of topical (top.) formulation for co‐delivery of cisplatin and imiquimod to enhance the antitumor efficacy of the drug for skin‐cited malignancies even in immune compromised patient. Cisplatin (CDDP) and imiquimod‐loaded protransfersome gel (CDDP‐Imi‐Pts gel) formulation was characterized for entrapment efficiency, pH, and viscosity. Further, fluorescence‐labeled (6‐carboxyfluorescin) and radiolabeled (^99mtechnetium) drug‐loaded formulations were compared with respect to biodistribution and pharmacokinetic studies. Gamma scintigraphy of mice following radiolabeled formulation administrations was performed to accomplish the localization of drugs in various organs. The percentage entrapment efficiency of cisplatin and imiquimod in the protransfersome gel formulations were found to be 36.22 ± 6.41 and 63.11 ± 3.73. The skin/blood localization ratio of 1.096, 120.13, 0.174, and 349.88 was found for intraperitoneal radiolabeled drug solution (^99m‐Tc‐CDDP‐Imi‐Sol), top. radiolabeled drug‐loaded protransfersome gel formulation (^99m‐Tc‐CDDP‐Imi‐Pts gel), intraperitoneal 6‐carboxyfluorescin labeled drug solution (6‐Cf‐CDDP‐Imi‐Sol), top. 6‐carboxyfluorescin labeled drug‐loaded protransfersome gel formulation (6‐Cf‐CDDP‐Imi‐Pts gel), respectively after 0.5h of administration. CDDP‐Imi‐Pts gel has a potential for site specific delivery and reduces the systemic toxicity of anti cancer drugs. These findings suggest that the cisplatin–imiquimod co‐delivery offers an attractive, novel approach for treatment of skin‐cited malignancies.     

Impacts of chemical enhancers on skin permeation and deposition of terbinafine

Abstract

Context/Objective: The addition of chemical enhancers into formulations is the most commonly employed approach to overcome the skin barrier. The objective of this work was to evaluate the effect of vehicle and chemical enhancers on the skin permeation and accumulation of terbinafine, an allylamine antifungal drug.

Methods: Terbinafine (1% w/w) was formulated as a Carbopol 934?P gel formulation in presence and absence of three chemical enhancers, nerolidol, dl-limonene and urea. Terbinafine distribution and deposition in stratum corneum (SC) and skin following 8-h ex vivo permeation study was determined using a sequential tape stripping procedure. The conformational order of SC lipids was investigated by ATR-FTIR spectroscopy.

Results and discussion: Nerolidol containing gel formulation produced significantly higher enhancement in terbinafine permeation through skin and its skin accumulation was increased. ATR-FTIR results showed enhancer induced lipid bilayer disruption in SC. Urea resulted in enhanced permeation of terbinafine across the skin and a balanced distribution to the SC was achieved. But, dl-limonene could not minimize the accumulation of terbinafine in the upper SC.

Conclusion: Nerolidol dramatically improved the skin permeation and deposition of terbinafine in the skin that might help to optimize targeting of the drug to the epidermal sites as required for both of superficial and deep cutaneous fungal infections.     

Novel gel formulations with catanionic aggregates enable prolonged drug release and reduced skin permeation

Objectives The aim of this study was to investigate skin permeation rates of a drug substance when applied in novel gel formulations with catanionic aggregates. Methods Reference gel without catanionic aggregates was compared with formulations with catanionic aggregates composed of tetracaine and either sodium dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare the effect of different gel types to elucidate if physically cross‐linked, ‘self‐destructing’ systems had benefits compared with classical, covalently cross‐linked, gels. Key findings The rheological investigation showed that the interactions between the SoftCAT polymer and tetracaine/SDS aggregates were stronger than when the tetracaine/capric acid aggregates were used. The skin permeation was measured ex vivo in horizontal Ussing chambers and the permeation of tetracaine was significantly lower when formulations with tetracaine/SDS aggregates were applied (P < 0.001), but not statistically different from the reference when capric acid was used. Conclusions No morphological differences could be distinguished between the skin samples exposed to the different formulations or the reference. Skin permeation was compared with silicone sheet permeation and the results indicated that silicone sheets could be used as a model of skin when using these formulations.     

Nanosized ethosomes bearing ketoprofen for improved transdermal delivery

The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrations of SPC and ethanol. The formulations exhibited entrapment efficiencies of 42–78%. In vitro release through cellophane membrane showed sustained release of drug from ethosomal formulations in contrast to hydroalcoholic drug solution (HA), which released most of the drug within 2–3 h. In vitro drug permeation across human skin revealed improved drug permeation and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero order drug release from formulations. Based on in vitro transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub therapeutic drug concentration with a patch size of 50 cm². Skin permeation of ethosomal formulations assessed by confocal microscopy revealed enhanced permeation of Rhodamine 123 loaded formulation in comparison to the hydroalcoholic solution.     

Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization,in vitro evaluation and preclinical assessment

The present investigation aimed for the development and characterization of ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery and effective treatment against vitiligo. The ethosomes were prepared by central composite design (CCD) and characterized for various quality attributes like vesicle shape, size, zeta potential, lamellarity, drug entrapment and drug leaching. The optimized ethosomes were subsequently incorporated int Carbopol® 934 gel and characterized for drug content, rheological behavior, texture profile, in vitro release, ex vivo skin permeation and retention, skin photosensitization and histopathological examination. Ethosomes were found to be spherical and multilamellar in structures having nanometric size range with narrow size distribution, and high encapsulation efficiency. Ethosomal formulations showed significant skin permeation and accumulation in the epidermal and dermal layers. The fluorescence microscopy study using 123 Rhodamine exhibited enhanced permeation of the drug-loaded ethosomes in the deeper layers of skin. Also, the developed formulation showed insignificant phototoxicity and erythema vis-à-vis the conventional cream. The results were cross-validated using histopathological examination of skin segments. In a nutshell, the ethosomes-based hydrogel formulation was found to be a promising drug delivery system demonstrating enhanced percutaneous penetration of methoxsalen with reduced phototoxicity and erythema, thus leading to improved patient compliance for the treatment against vitiligo.     

Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies

Abstract

Cetirizine is indicated for the treatment of allergic conditions such as insect bites and stings, atopic and contact dermatitis, eczema, urticaria. This investigation deals with development of a novel ethosome-based topical formulation of cetirizine dihydrochloride for effective delivery. The optimised formulation consisting of drug, phospholipon 90 G? and ethanol was characterised for drug content, entrapment efficiency, pH, vesicular size, spreadability and rheological behaviour. The ex vivo permeation studies through mice skin showed highest permeation flux (16.300?±?0.300?µg/h/cm²) and skin retention (20.686?±?0.517?µg/cm²) for cetirizine-loaded ethosomal vesicles as compared to conventional formulations. The in vivo pharmacodynamic evaluation of optimised formulation was assessed against oxazolone-induced atopic dermatitis (AD) in mice. The parameters evaluated were reduction in scratching score, erythema score, skin hyperplasia and dermal eosinophil count. Our results suggest that ethosomes are effective carriers for dermal delivery of antihistaminic drug, cetirizine, for the treatment of AD.     

Topical delivery of α-interferon from liposomal systems: an in vivo study with hairless mouse

Abstract

The deposition of a-interferon into living skin strata of hairless mouse following topical in vivo application of a glyceryl dilaurate: POE-10: cholesterol liposomal formulation was much higher than from a glyceryl distearate: POE-10: cholesterol liposomal formulation or from an aqueous solution. The kinetics and extent of drug deposition from the liposomal formulations appear to correspond to the extent of release of bilayer lipid components following topical application and subsequent action of the lipid components as skin permeation enhancers.     

Topical gels of etofenamate: in vitro and in vivo evaluation

Abstract

Non-steroid anti-inflammatory drugs (NSAIDs), such as etofenamate, are among the most prescribed drugs used for their analgesic, anti-rheumatic, antipyretic and anti-inflammatory properties. Topical formulations have the main advantage of targeted delivery. However, drugs must overcome the skin due to its role as a physical and chemical barrier against the penetration of chemicals and microorganisms. This barrier must be altered to allow the permeation of drugs at a suitable rate to the desired site of activity. Permeation modulators can intercalate the skin outer layers causing structure disruption, opening an energetically favourable route for the drug to diffuse through. The aim of this work was the development of hydroalcoholic gels containing 5.0% (w/w) of etofenamate for topical administration with anti-inflammatory activity and enhanced drug delivery. The physical and chemical characterization, in vitro release and permeation studies and in vivo anti-inflammatory activity were assessed. The gel with 30% ethanol showed in vivo anti-inflammatory activity with suitable physical chemical and microbiologic characteristics. In vitro release and permeation studies revealed that the different amounts of ethanol used influenced the release profiles of etofenamate. Moreover, it was demonstrated that this formulation is an adequate vehicle for the etofenamate skin permeation.     

Comparative study of liposomes,transfersomes and ethosomes as carriers for improving topical delivery of celecoxib

Topical administration of celecoxib proved to be an effective mean of preventing skin cancer development and improving anticancer drugs effectiveness in skin tumors treatment. The aim of this study was the development of an effective topical formulation of celecoxib, able to promote drug skin delivery, providing its in depth penetration through the skin layers. Three kinds of vesicular formulations have been investigated as drug carriers: liposomes containing a surfactant, or transfersomes and ethosomes, containing suitable edge activators. Firstly, the effect of membrane composition variations on the system performance has been evaluated for each vesicle type. Selected formulations were characterized for particle size, polydispersity index and encapsulation efficiency. The best formulations were subjected to ex vivo permeation studies through excised human skin. All vesicular formulations markedly (p < 0.001) improved the drug amount penetrated into the skin with respect to an aqueous suspension, from 2.0 to 6.5, up to 9.0 folds for liposomes, transfersomes and ethosomes, respectively. In particular, ethosomes containing Tween 20 as edge activator not only showed the best vesicle dimensions and homogeneity, and the highest encapsulation efficacy (54.4%), but also enabled the highest increase in drug penetration through the skin, probably due to the simultaneous presence in their composition of ethanol and Tween 20, both acting as permeation enhancers. Therefore, among the various vesicular formulations examined in the study, Tween 20-ethosomes can be considered the most promising one as carrier for topical celecoxib applications aimed to prevent skin cancer development and increase the anticancer drugs effectiveness against skin tumors.     

Pig Ear Skin ex Vivo as a Model for in Vivo Dermatopharmacokinetic Studies in Man

Objective The objective was to investigate pig ear skin as a surrogate for human skin in the assessment of topical drug bioavailability by sequential tape-stripping of the stratum corneum (SC). The potential benefits of ex vivo investigations are manifold: ethical approval is not required, multiple replicate experiments are more easily performed, and toxic compounds can be evaluated.Materials and Methods Ex vivo experiments on isolated pig ears were compared with in vivo studies in human volunteers. Four formulations, comprising the model drug, ibuprofen, in different propylene glycol (PG)-water mixtures (25:75, 50:50, 75:25 and 100:0), were compared.Results Derived dermatopharmacokinetic parameters characterizing the diffusion and partitioning of the drug in the SC ex vivo were consistent with those in vivo following a 30-minute application period. Further, the non-steady-state ex vivo results could be used to predict the in vivo concentration profile of the drug across the SC when a formulation was administered for 3 h (i.e., close to steady-state).Conclusions Taken together, the results obtained suggest that pig ear skin ex vivo has promise as a tool for topical formulation evaluation and optimization.     

Transdermal therapeutic system of isradipine: Effect of hydrophilic and hydrophobic matrix on <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">Ex vivo</Emphasis> characteristics

Isradipine (ISDP) is an effective calcium channel blocker used in the treatment of hypertension. It undergoes extensive first pass metabolism and bioavailability through the oral route is only about 15 to 24%. Hence we attempted to develop a matrix type controlled transdermal drug delivery system for ISDP. Formulations A1, A2, A3 were composed of Eudragit RL100 and hydroxypropyl methyl cellulose (HPMC) in 1:3, 1:1, 3:1 ratios; A4, A5, A6 were composed of Eudragit RS100 and HPMC in 1:3, 1:1, 3:1 ratios. All six formulations carried 5 mg of ISDP/patch area, 5% v/w of D-limonene, 15 % v/w of propylene glycol in methanol:dichloromethane (1:1). The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy and differential scanning calorimetry. The results suggested no physicochemical incompatibility between the drug and the polymers. The prepared transdermal drug delivery system were evaluated for physicochemical characteristics, mainly in vitro release and ex vivo permeation. The ex vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. All the formulations exhibited satisfactory physicochemical characteristics. Cumulative amount of the drug released in 36 h from the six formulations were 1695.32, 1527.89, 1455.54, 1485.65, 1282.81 and 916.88 μg/cm² respectively. Corresponding values for the cumulative amounts of drug permeated across the rat skin for the above matrix films were 1456.29, 1284.70, 1182.99, 1212.72, 1046.05, and 782.60 μg/cm² respectively. By fitting the data into zero order, first order and Higuchi models, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of drug release was diffusion mediated. Based on the physical evaluation, in vitro drug release and ex vivo permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films A1, may be suitable for the development of a transdermal drug delivery system of ISDP.     

QbD-based carbopol transgel formulation: characterization,pharmacokinetic assessment and therapeutic efficacy in diabetes

In order to develop transdermal drug delivery system that facilitates the skin permeation of Pioglitazone (PZ) encapsulated in carbopol-based transgel system (proniosomes/niosome). The developed formulations were optimized using quality by design (QbD) approach and particle size, percentage entrapment and transdermal flux were determined. It was found to be more efficient delivery carriers with high encapsulation and enhanced flux value demonstrated that the permeation of PZ through skin was significantly increased with developed formulation. The transdermal enhancement from proniosome was 3.16 times higher than that of PZ from control formulation (ethanol buffer formulation, 3:7), which was further confirmed by confocal laser scanning microscopy. In vivo pharmacokinetic study of carbopol transgel showed a significant increase in bioavailability (2.26 times) compared with tablet formulation. It also showed better antidiabetic activity in comparison to marketed tablet, so our results suggest that carbopol-based transgel are an efficient carrier for delivery of pioglitazone through skin.     

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.     

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.     

Evaluation of progesterone permeability from supercritical fluid processed dispersion systems

Abstract

The aim of this study was to investigate the permeability of unique dispersion systems prepared by supercritical fluid (SCF) processing, to deliver bioidentical progesterone (PGN) across mouse skin. Semisolid dispersions of PGN were made up of either polyethylene glycol (PEG) 400/4000, Gelucire 44/14, d-α-tocopheryl PEG 1000 succinate (TPGS), tanscutol P or myritol 318. SCF dispersion systems were compared with various control formulations; a market cream, aqueous suspension, and three conventionally prepared dispersions comelted, cosolvent and physically mixed systems. The permeability coefficient in the absence or presence of a permeation enhancer was evaluated using ex vivo mouse skin. The permeation study results for the TPGS/myritol/transcutol P dispersion system prepared using supercritical carbon dioxide (SC-CO₂) had a two-fold improvement in transdermal permeation over 24?h compared to the control formulation, 245.7 and 126?µg?cm^?2, respectively (p value?<?0.05). In this study, the skin integrity and morphology was also investigated for changes due to the formulation constituents using histological examination and Fourier transform infrared spectroscopy. The particles from the gas-saturated suspension method and SC-CO₂ together with TPGS/myritol/transcutol P may offer potential advantages over the available cream on the market based on the vastly improved lag time and flux of PGN across the skin.     

Investigation of true nanoemulsions for transdermal potential of indomethacin: characterization,rheological characteristics,and ex vivo skin permeation studies

The aim of the present study was to investigate the potential of true nanoemulsions for transdermal delivery of indomethacin. Thermodynamically stable true nanoemulsions were characterized for morphology using transmission electron microscopy (TEM), droplet size, rheological characteristics, and refractive index. The rheological behavior for all true nanoemulsions was found to be Newtonian as viscosity was unchanged by increasing the rate of shear. The ex vivo skin permeation studies were performed using Franz diffusion cell with rat skin as permeation membrane. The ex vivo skin permeation profile of optimized formulation was compared with marketed Indobene gel and nanoemulsion gel. Significant increase in permeability parameters was observed in nanoemulsion formulations (P?<?0.05). The steady-state flux (J_ss) and permeability coefficient (K_p) for optimized nanoemulsion formulation were found to be 73.96?±?2.89?μg/cm²/h and 1.479?×?10^?2?±?0.289?×?10^??2?cm/h, respectively, which were significant compared with Indobene gel and nanoemulsion gel (P?<?0.05). Enhancement ratio (E_r) was found to be 7.88 in optimized formulation F6 compared with other formulations. These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of indomethacin.     

Liquid crystalline Pluronic 105 pharmacogels as drug delivery systems: preparation,characterization, and in vitro transdermal release

In this study, we report the results of our investigations on the percutaneous permeation profiles of Diclofenac sodium, Paracetamol, Propanolol hydrochloride, and α-Tocopherol from the different lyotropic liquid crystalline phases obtained by Pluronic P105/water mixtures, in order to understand if the particular assembly shown in the formulations could influence the delivery across the skin.

Recent studies have focused on the Pluronic liquid crystalline phases to evaluate the potential use of these phases in drug delivery, but no comparative investigation has been yet performed on the drug permeation from the different liquid crystalline phases obtained by the same Pluronic surfactant.

The cubic, hexagonal, and lamellar mesophases (loading the above-mentioned drug) were characterized by Deuterium Nuclear Magnetic Resonance spectroscopy and Polarized Optical Microscopy observations. Results revealed that the liquid crystalline gel microscopic structure obtained in the different formulations drastically affects the drug percutaneous availability. As a consequence these systems could be proposed as novel transdermal drug delivery systems.     

Transfersomes: A Novel Vesicular Carrier for Enhanced Transdermal Delivery of Sertraline: Development,Characterization, and Performance Evaluation

The aim of the present study was to investigate transfersomes as a transdermal delivery system for the poorly soluble drug, sertraline, in order to overcome the troubles associated with its oral delivery. Different transfersomal formulations were prepared with non-ionic surfactant (span 80), soya lecithin, and carbopol 940 by the rotary evaporation sonication method. The prepared formulations were characterized for light microscopy, particle size analysis, drug entrapment, turbidity, drug content, rheological studies, in vitro release, ex vivo permeation, and stability studies. The optimized formulation was evaluated for in vivo studies using the modified forced swim model test. FTIR studies showed compatibility of the drug with excipients. The result revealed that sertraline in all of the formulations was successfully entrapped with uniform drug content. Transfersomal gel containing 1.6% of the drug and 20% of span 80 was concluded to be the optimized formulation (EL-SP4), as it showed maximum drug entrapment (90.4±0.15%) and cumulative percent drug release(73.8%). The ex vivo permeation profile of EL-SP4 was compared with the transfersomal suspension, control gel, and drug solution. The transfersomal gel showed a significantly higher (p<0.05) cumulative amount of drug permeation and flux along with lower lag time than the drug solution and drug gel. It also owed to better applicability due to the higher viscosity imparted by the gel rather than the transfersomal suspension, and no skin irritation was observed. The modified forced swim test in mice revealed that the transfersomal gel had better antidepressant activity as compared to the control gel. Thus, the study substantiated that the transfersomal gel can be used as a feasible alternative to the conventional formulations of sertraline with advanced permeation characteristics for transdermal application.