Design,development, physicochemical,in vitro and in vivo evaluation of monolithic matrix type transdermal patches containing nitrendipine

The matrix type transdermal drug delivery systems (patches) of Nitrendipine were prepared by film casting technique. The patches were characterized for physical, in vitro release studies and ex-vivo permeation studies (human cadaver skin). On the basis of in vitro drug release and skin permeation performance, formulation B3 was found to be better than the other formulations and it was selected as the optimized formulation. The final optimized formulation (B3) was subjected to skin irritation, pharmacokinetic, pharmacodynamic and stability studies. The maximum percentage drug release in 48 hours was 94.67 ± 3.25 for B3 and 91.43 ± 2.106 for A2 formulation. Again formulation B3 (0.0627 mg/cm²/h) and A2 (0.0566 mg/cm²/h) showed maximum skin flux in the respective series. Patches prepared with Plasdone S-630 were more flexible as compared to PVP K 30 containing patches. Patches prepared with PVP K 30 showed drug release and skin permeation at higher percentage as compared to those containing Plasdone S-630. The interaction studies carried out by comparing the results of ultraviolet, infrared, TLC and DSC analyses for the pure drug, medicated and placebo formulations indicated no chemical interaction between the drug and excipients. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (< 2.00) under Draize score test.     

Ethogel topical formulation for increasing the local bioavailability of 5-fluorouracil: a mechanistic study

5-Fluorouracil (5-FU) is an anticancer drug and is considered a gold standard for the treatment of skin cancer. At present, topical chemotherapy with 5-FU is associated with the limitations of poor skin permeation, retention at target site, and skin irritation potential. In the present study, an attempt has been made to develop an ethosome-based topical gel formulation (ethogel) for skin targeting of 5-FU. The ethosomal formulation was prepared using the classical dispersion method, and loading of 5% w/w of the drug was optimized to the commercial strength of marketed 5-FU cream. Carbopol 934P was used as a gel former in 0.5, 0.75, 1.0, and 1.5% w/w concentration for preparation of ethosome-based ethogel formulation. The ethogel formulation was characterized for viscosity, spreadability, extrudability, and pH. Viscosity of the developed ethogel and that of the marketed formulation was found to be 3070±14.7 and 2870±14.4 cP, respectively. An in-vitro skin permeation and deposition study was carried out across rat skin using the marketed cream and 5-FU drug solution as controls. The amount of drug deposition was found to increase 5.9- and 9.4-fold on treatment with ethogel in comparison with the marketed cream and drug solution, respectively. The result of antitumor activity evaluated using a Cytoselect 96-well cell transformation assay revealed a large reduction in tumor density with treatment with the 5-FU ethogel formulation in comparison with the marketed formulation. A significant reduction in the skin irritation potential of 5-FU ethogel formulation was also found in comparison with that of the marketed formulation as measured by the Draize test. The results of the present study demonstrated ethogel as a better alternative for increasing the local bioavailability of 5-FU in comparison to the marketed formulation.     

Transdermal drug delivery systems of a beta blocker: design, in vitro, and in vivo characterization

The matrix type transdermal drug delivery systems (TDDS) of metoprolol were prepared by film casting technique using a fabricated stainless steel film casting apparatus and characterized in vitro by drug release, skin permeation, skin irritation, and in vivo pharmacodynamic and stability studies. Four formulations were prepared that differed in the ratio of matrix forming polymers. Formulations M-1, M-2, M-3, and M-4 were composed of Eudragit RL-100 and polyvinyl acetate with the following ratios: 2:8, 4:6, 6:4, and 8:2, respectively. All the four formulations carried 10% (w/w) of metoprolol tartrate, 5% (w/w) of dibutylphthalate, and 5% (w/w) of (+/-) menthol in dichloromethane:isopropyl alcohol (80:20 v/v). Cumulative amount of drug released in 48 hr from the four formulations was 79.16%, 81.17%, 85.98%, and 95.04%. The corresponding values for cumulative amount of drug permeated for the said formulations were 59.72%, 66.52%, 77.36%, and 90.38%. On the basis of in vitro drug release and skin permeation performance, formulation M-4 was found to be better than the other three formulations and it was selected as the optimized formulation. The formulation appeared to be stable when stored at 40 degrees C and 75% RH with negligible degradation of the drug. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (<2.00) under Draize score test. Statistically significant reduction in mean blood pressure (p < .01) was achieved in methyl prednisolone-induced hypertensive rats on treatment with the TDDS.     

Olive oil and clove oil-based nanoemulsion for topical delivery of terbinafine hydrochloride: in vitro and ex vivo evaluation

In this article, formulation studies for terbinafine hydrochloride nanoemulsions, prepared by high-energy ultrasonication technique, are described. Pseudo-ternary phase diagram was constructed in order to find out the optimal ratios of oil and surfactant/co-solvent mixture for nanoemulsion production. Clove and olive oils were selected as oil phase. Based on the droplet size evaluation, maximum nanoemulsion region were determined for formulation development. Further characterization included polydispersity index (PDI), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, morphology, pH, viscosity, refractive index, ex vivo skin permeation, skin irritation, and histopathological examination. Droplet sizes of optimized formulations were in colloidal range. PDI values below 0.35 indicated considerably homogeneous nanoemulsions. Zeta potential values were from 13.2 to 18.1 mV indicating good stability, which was also confirmed by dispersion stability studies. Ex vivo permeation studies revealed almost total skin permeation of terbinafine hydrochloride from the nanoemulsions (96–98%) in 6 hours whereas commercial product reached only 57% permeation at the same time. Maximum drug amounts were seen in epidermis and dermis layers. Skin irritation and histopathological examination demonstrated dermatologically safe formulations. In conclusion, olive oil and clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.     

Pluronic lecithin organogel as a topical drug delivery system

The objective of this study was to formulate and evaluate the pluronic lecithin organogel containing flurbiprofen for topical application. Different formulations of pluronic lecithin organogels were prepared by using pluronic F127, lecithin, flurbiprofen, isopropyl palmitate, water, sorbic acid, and potassium sorbate. To study the in vitro potential of these formulations, permeation studies were performed with Keshary-Chien diffusion cells. The results of the in vitro permeation studies found that release of flurbiprofen from dialysis membrane-70 was more than excised dorsal rat skin. Gelation temperature study was carried out to determine the temperature where sol-gel transformation takes place. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°C, the viscosity of formulations increases as the lecithin concentration increases. Also the formulations were tested for appearance and feel psychorheologically, pH, and drug content. Interactions between the components of the gel have been investigated by differential scanning calorimetry and X-ray powder diffractometry. The optimized formulation subjected to differential scanning calorimetry shows no drug–polymer interaction. To investigate the in vivo performance of the formulations, a carrageenan-induced rat paw edema model and skin irritation study was used. The stability studies and freeze–thaw thermal cyclic test were carried out, showing no phase separation of gel, and representing gel stability. Statistical analysis of the data of animal study (anti-inflammatory activity) was done by using one way analysis of variance (ANOVA) followed by Dunnett’s test. The formulation shows a statistically significant anti-inflammatory activity and is non-irritant to skin.     

Pluronic lecithin organogel as a topical drug delivery system

The objective of this study was to formulate and evaluate the pluronic lecithin organogel containing flurbiprofen for topical application. Different formulations of pluronic lecithin organogels were prepared by using pluronic F127, lecithin, flurbiprofen, isopropyl palmitate, water, sorbic acid, and potassium sorbate. To study the in vitro potential of these formulations, permeation studies were performed with Keshary-Chien diffusion cells. The results of the in vitro permeation studies found that release of flurbiprofen from dialysis membrane-70 was more than excised dorsal rat skin. Gelation temperature study was carried out to determine the temperature where sol-gel transformation takes place. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°C, the viscosity of formulations increases as the lecithin concentration increases. Also the formulations were tested for appearance and feel psychorheologically, pH, and drug content. Interactions between the components of the gel have been investigated by differential scanning calorimetry and X-ray powder diffractometry. The optimized formulation subjected to differential scanning calorimetry shows no drug-polymer interaction. To investigate the in vivo performance of the formulations, a carrageenan-induced rat paw edema model and skin irritation study was used. The stability studies and freeze-thaw thermal cyclic test were carried out, showing no phase separation of gel, and representing gel stability. Statistical analysis of the data of animal study (anti-inflammatory activity) was done by using one way analysis of variance (ANOVA) followed by Dunnett's test. The formulation shows a statistically significant anti-inflammatory activity and is non-irritant to skin.     

Evaluation of topical econazole nitrate formulations with potential for treating Raynaud’s phenomenon

The purpose of this work was to design and characterize a topical formulation of econazole nitrate (EN) with potential for treating Raynaud’s phenomenon (RP). Four topical dosage forms (F1_topical solution, F2_HPMC or hydroxypropyl methylcellulose dispersion, F3_VersaBase^® cream, and F4_{_}Lipoderm^® Activemax? Cream) containing 3% w/w EN were prepared and characterized for drug content, pH, viscosity, spreadability, drug crystallinity, stability, and in vitro permeation using Franz cells across pig ear skin, and results were compared to the 1% marketed EN cream. All four formulations had acceptable physical and visual characteristics required for topical application, with 3% w/w EN. The order of amount of drug permeated from highest to lowest was F2 (10.27%) > F4 (2.47%) > F1 (2.28%) > F3 (1.47%) > marketed formulation (0.22%). Formulation F2 showed better penetration of the drug into the stratum corneum, epidermis, and dermis layers. The drug concentration in the stratum corneum and epidermis was approximately 10–20 times higher with F2 compared to the marketed formulation. All formulations were found to be stable for up to 6 months. All four EN formulations were found to be better than the 1% marketed cream. Formulation F2_{_}HPMC dispersion could be further explored as a treatment option for RP.     

Ketotifen Fumarate and Salbutamol Sulphate Combined Transdermal Patch Formulations: In vitro release and Ex vivo Permeation Studies

The present work was performed to develop and evaluate transdermal patches of combined antiasthmatic drugs (salbutamol sulphate and ketotifen fumarate). Polyvinyl alcohol membrane was used as backing membrane and eudragit RL-100 was used as matrix material to suspend the drugs in the continuous thickness of the patch. Methanol was solvent and propylene glycol was used as plasticizer. Tween 20, isopropyl myristate, eucalyptus oil, castor oil and span-20 were used as permeability enhancers. Thickness, weight variation and drug uniformity were investigated. The patch formulations were also subjected to drug release in dissolution media and permeation through rabbit skin. Effects of different enhancers were evaluated on release and permeation of drugs. F3 formulations having isopropyl myristate as permeation enhancer, showed maximum amounts of drugs release (88.11% of salbutamol sulphate and 88.33% of ketotifen fumarate) at the end of 24 h dissolution study. F3 also showed maximum permeation of both drugs (4.235 mg salbutamol sulphate and 1.057 mg ketotifen fumarate) after 24 h permeation study through rabbit skin mounted in Franz cell. The patches having no enhancer in the formulation also showed some drug release and permeation due to the presence of plasticizer. The results of the study suggested that new controlled release transdermal formulations of combined antiasthmatic drugs can be suitably developed as an alternate to conventional dosage forms.     

Skin Irritation in Transdermal Drug Delivery Systems: A Strategy for its Reduction

Purpose Active pharmaceutical ingredients (API) in transdermal drug delivery systems (TDS) often causes skin irritation such as erythema and edema. We have studied a possible approach for the reduction of skin irritation by patch formulations that control the rates of skin permeation and elimination of API. Methods Loxoprofen (LX-base) was used to induce the skin irritation. The redness value (Δa) was evaluated as a measure of erythema by Chroma Meter. The in vitro skin permeation and release profiles were also investigated by using a side-by-side diffusion cell. Results The redness values were not correlated either with the cumulative amount of API permeated or the concentration of LX-base in the skin, but well correlated with the elimination rate of LX-base from the skin after the removal of the formulation. The formulation with gradual decrease of permeation rate during application accelerated the elimination rate after application, and resulted in the reduction of the skin irritation. Conclusions The skin pharmacokinetics of API, not only permeation during application but also release after the patch removal, was found to be a significant factor for skin irritation. To minimize the skin irritation, it’s also important to eliminate the residual API in the skin promptly after application.     

Skin permeation of physostigmine from fatty acids-based formulations: evaluating the choice of solvent

This study was conducted to gain an understanding of the enhancement mechanism of fatty acids in skin permeation of physostigmine (PHY) by using a series of fatty acids and two solvents of opposing lipophilicity (propylene glycol (PG) and mineral oil (MO)). Interaction between fatty acid and drug was proven using NMR and conductivity measurements that showed a dependence on type of solvent used. Permeation flux of physostigmine from mineral oil-based formulations to skin was increased as solubility of physostigmine in mineral oil was enhanced in the presence of fatty acids having a longer chain. Thus, the dominant role of fatty acids in mineral oil was to increase solubility of physostigmine in the formulations that increased the driving force for physostigmine permeation through skin. As for propylene glycol, enhancement caused by fatty acids was attributed to their ability to increase the lipophilicity of formulation and to disrupt the lipid bilayers within the stratum corneum (SC). In conclusion, fatty acids enhancement for drug permeation across the skin was found to be dependent on the solvent used. Among various formulations here, oleic acid in mineral oil yielded fast permeation of PHY with a short lag time, which may be a good vehicle for transdermal delivery of PHY.     

特比萘芬乳凝胶的制备及质量评价

目的:制备特比萘芬乳凝胶并对其质量进行评价。方法:以溶解度为指标筛选乳化剂和油相,以不同微乳体系的三元相图筛选油相、乳化剂和助乳化剂的用量,采用直接溶胀法制备乳凝胶,并对其含量、体外经皮渗透性、皮肤刺激性、稳定性进行考察。结果:乳凝胶的最优处方(100 g)为丙二醇辛酸酯14.0 g、聚氧乙烯-35-蓖麻油40.0 g、丙二醇2.0 g。制备的特比萘芬乳凝胶含量合格,12 h的体外累积渗透量为(1 283.7±33.5)μg/cm2,皮肤刺激反应评分24 h为0.1、48 h为0(无刺激),稳定性各项指标无明显变化。结论:该制剂制备处方合理,质量可控。     

Localized delivery of paclitaxel using elastic liposomes: formulation development and evaluation

In the present study an elastic liposomes-based paclitaxel formulation was developed with the objective to remove Cremophor EL. Cremophor EL is currently used for solubilizing paclitaxel in the marketed formulation and is known to produce toxic effects. Elastic liposomal paclitaxel formulation was extensively characterized in vitro, ex-vivo, and in vivo. The results obtained were compared against the marketed paclitaxel formulation. The maximum amount of paclitaxel loaded in the elastic liposomal formulation was found to be 6.0 mg/ml, which is similar to the commercial strength of marketed paclitaxel formulation. In vitro skin permeation and deposition studies showed 10.8-fold enhanced steady state transdermal flux and 15.0-fold enhanced drug deposition in comparison to drug solution. These results further confirmed with the vesicle-skin interaction study using FTIR technique. Results of the hemolytic toxicity assay indicate that elastic liposomal formulation induced only 11.2 ± 0.2% hemolysis in comparison to the commercial formulation which showed 38 ± 3.0%. Further, results of the Draize test showed no skin irritation of paclitaxel elastic liposomal formulation. Findings of the study demonstrate that elastic liposomes as a carrier is an attractive approach for localized delivery of paclitaxel.     

Localized delivery of paclitaxel using elastic liposomes: Formulation development and evaluation

In the present study an elastic liposomes-based paclitaxel formulation was developed with the objective to remove Cremophor EL. Cremophor EL is currently used for solubilizing paclitaxel in the marketed formulation and is known to produce toxic effects. Elastic liposomal paclitaxel formulation was extensively characterized in vitro, ex-vivo, and in vivo. The results obtained were compared against the marketed paclitaxel formulation. The maximum amount of paclitaxel loaded in the elastic liposomal formulation was found to be 6.0?mg/ml, which is similar to the commercial strength of marketed paclitaxel formulation. In vitro skin permeation and deposition studies showed 10.8-fold enhanced steady state transdermal flux and 15.0-fold enhanced drug deposition in comparison to drug solution. These results further confirmed with the vesicle–skin interaction study using FTIR technique. Results of the hemolytic toxicity assay indicate that elastic liposomal formulation induced only 11.2?±?0.2% hemolysis in comparison to the commercial formulation which showed 38?±?3.0%. Further, results of the Draize test showed no skin irritation of paclitaxel elastic liposomal formulation. Findings of the study demonstrate that elastic liposomes as a carrier is an attractive approach for localized delivery of paclitaxel.     

Formulation and evaluation of mefenamic acid emulgel for topical delivery

Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. The objective of the study was to prepare emulgel of mefenamic acid, a NSAID, using Carbapol 940 as a gelling agent. Mentha oil and clove oil were used as penetration enhancers. The emulsion was prepared and it was incorporated in gel base. The formulations were evaluated for rheological studies, spreading coefficient studies, bioadhesion strength, skin irritation studies, in vitro release, ex vivo release studies, anti-inflammatory activity and analgesic activity. Formulation F2 and F4 showed comparable analgesic and anti-inflammatory activity when they compared with marketed diclofenac sodium gel. So, it can be concluded that topical emulgel of mefenamic acid posses an effective anti-inflammatory and analgesic activity.     

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.     

Influence of the formulation on the in vitro transdermal penetration of sodium diclofenac. Evaluation of the topical and systemic anti-inflammatory activity in the rat

A study on the transdermal permeation through human skin was performed with a series of 6 semisolid formulations (A-F) containing 1% sodium diclofenac (CAS 15307-79-6) (w/w). A commercially available drug preparation was tested as a reference. Based on permeation characteristics, a study on the topical and systemic anti-inflammatory activities of three formulations (A, F and the reference formulation) was conducted using the model of erythema induced by UV radiation in hairless rats. This is expected, together with the index of topical anti-inflammatory activity to allow the selection of the most suitable formulation for dermal application. The following representative parameters were measured in the permeation study: amount of diclofenac permeated at 24 h, flow, lag time and amount of drug retained in skin at 24 h. Of the formulations tested, diclofenac formulated in the reference formulation showed the highest values of amount of diclofenac permeated at 24 h, amount of drug retained in skin at 24 and flow. As regards the skin inflammation test, no significant differences (p < 0.05) are seen between the topical and systemic anti-inflammatory activities of the three formulations tested. However, in absolute value, formulation F shows a lower systemic activity, which would prevent potential side effects of diclofenac. Since the topical anti-inflammatory index obtained for this formulation was > 1, it is concluded that a good therapeutic performance could be obtained in the treatment of local inflammation with diclofenac by using formulation F.     

Design, development and optimization of nimesulide-loaded liposomal systems for topical application

Nimesulide, a non-steroidal anti-inflammatory drug, was incorporated into multilamellar liposomes to improve its performance on topical administration. The drug was loaded onto liposomes employing thin film hydration technique. Various process and formulation variables were investigated to obtain the liposomal products of desired quality. Liposomes were monitored for percent drug entrapment, after separating the unentrapped drug by mini column centrifugation, for vesicular properties (such as size distribution profile, morphological attributes and agglomeration tendency), drug diffused through synthetic semipermeable membrane, and drug leakage. Systematic optimization studies were carried out using 3(2) factorial design to select the optimized liposomal composition with reference to percent drug entrapment, drug diffusion and leakage. The optimized batch of liposomes was subjected to drug permeation and drug retention studies employing rat skin and human cadaver skin. In comparison to methanolic solution of pure nimesulide, liposomal formulations were found to retain higher amounts of nimesulide in the skin. Anti-inflammatory studies, using carragenan-induced rat paw edema model, indicated significantly better performance of liposomally entrapped nimesulide in comparison to the marketed gel formulation and the Carbopol gel containing nimesulide.     

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.     

Enhance transdermal delivery of flurbiprofen via microemulsions: Effects of different types of surfactants and cosurfactants

Background and the purpose of the study

Microemulsions are thermodynamically stable, clear dispersions of water, oil, surfactant, and cosurfactant. This study was aimed to develop flurbiprofen microemulsion for enhanced transdermal delivery and investigate the effects of different surfactants and cosurfactants on its delivery and phase behavior.

Method

Various surfactant-cosurfactant mixtures in ratio of 2:1 (Smix) along with oleic acid (oil) were selected and phase diagrams were constructed. Six microemulsions each containing 5% drug, 5% oil, 56% Smix and 34% water, were prepared and compared for their permeation and phase behaviors to determine the effects of the type of Smix.

Results

In vitro transdermal permeation through rabbit skin of all microemulsions was high than saturated aqueous drug solution. Tween 20 and ethanol as Smix produced the highest flux amongst all the Smix, and were used to prepare formulations with different values of oil and Smix. While the type of surfactant did not affect the droplet size, propylene glycol as cosurfactant produced the largest droplets and highest viscosity. Decrease in oil or Smix concentration resulted in decrease of the droplet size and increase in permeation flux while decrease in viscosity also increased the permeation flux of microemulsions. Finally the selected microemulsion formulation comprising 5% flurbiprofen, 5% oleic acid, 46% Tween 20:ethanol (2:1) and 44% water, showed the highest transdermal flux and caused no skin irritation.

Conclusion

Type of surfactant and cosurfactant affect both the phase behavior and transdermal drug delivery of microemulsion; and results of this study showed that they are promising vehicles for improved transdermal delivery and sustained action of flurbiprofen.     

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.