Pretreatment with Skin Permeability Enhancers: Importance of Duration and Composition on the Delivery of Diclofenac Sodium

The use of chemical penetration enhancers (CPEs) is one of the most common approaches to improve the dermal and transdermal delivery of drugs. However, often, incorporation of CPEs in the formulation poses compatibility and stability challenges. Moreover, incorporation of enhancers in the formulation leads to prolonged exposure to skin increasing the concern of causing skin reactions. This study was undertaken to assess whether pretreatment with CPEs is a rational approach to enhance the permeation of diclofenac sodium. In vitro experiments were performed across porcine epidermis pretreated with propylene glycol or oleic acid or their combinations for 0.5, 2, and 4 h, respectively. Pretreatment with combination of oleic acid in propylene glycol was found to enhance the permeation of diclofenac sodium significantly only at 10% and 20% (v/v) level, and only when the pretreatment duration was 0.5 h. Longer durations of pretreatment and higher concentration of oleic acid in propylene glycol did not enhance the permeation of diclofenac sodium. In vivo dermatokinetic studies were carried out on Sprague–Dawley rats. A twofold increase in AUC and C_max was observed in case of rats pretreated with enhancers over the group that was pretreated with buffer. In conclusion, this study showed that composition of the enhancers and duration of pretreatment are crucial in determining the efficacy of CPEs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.     

新型经皮传递胰岛素透明质酸微针制剂的制备及性能考察

目的证明透明质酸微针制剂在药物经皮传递系统方面的应用前景。方法通过皮肤及微针的显微照片考察微针刺入皮肤的性能和在大鼠体内的溶解性能;用皮肤刺激性实验评价透明质酸微针的安全性;以人的离体皮肤为透皮释药模型,通过体外经皮通透实验考察微针对模型药物胰岛素经皮吸收的促进作用。结果微针能够均匀刺穿角质层,在皮肤表面产生与微针一致的阵列形状,在皮肤断面可观察到直至真皮层的通道;在大鼠体内使用1 h后,针体能够完全溶解,皮肤刺激性指数为1.7,属于轻度刺激性;体外经皮实验中,微针中的胰岛素能够以活性形式释放,与同剂量的溶液相比,微针对胰岛素的体外经皮吸收具有显著的促进作用,稳态通透速率达75.33×10-6U.cm-2.h-1。结论以透明质酸为基质制备的微针具有良好的皮肤刺入性、溶解性和轻度的刺激性,对于生物大分子类药物的经皮吸收有明显的促进作用,具有良好的开发前景。     

Transdermal Delivery of Sumatriptan Succinate Using Iontophoresis and Dissolving Microneedles

This study focuses on the in vitro transdermal transport of sumatriptan succinate using combined iontophoresis and dissolving polymeric microneedle arrays. Permeation experiments were performed to evaluate the effects of formulation parameters on drug release from polyvinylpyrrolidone systems under mild electrical current (≤500 μA/cm²). The preparations consisted of hydrophilic, positively charged molecules encapsulated in a water-soluble and biocompatible polymeric material. Current densities of 100, 300, and 500 μA/cm² were applied during a 6-h period using silver/silver chloride electrodes. The circular array consisted of 600 needles and occupied a 0.785 cm² area. Tests, carried out with Franz diffusion cells and skin of Göttingen minipigs, showed that small decreases in the polymer concentration led to negligible lag times and marked increases in the cumulative amount of drug permeated in 6 h (Q_6h) and in the flux (J_ss). At 500 μA/cm², Q_6h and J_ss nearly doubled for a microneedle loaded with 5% (w/w) sumatriptan and 20% (w/w) PVP (lag time = 0 min; Q_6h = 2888 μg/cm²; J_ss = 490 μg/cm²/h) relative to a system loaded with 5% (w/w) drug and 30% (w/w) PVP (lag time = 36 min; Q_6h = 1437 μg/cm²; J_ss = 266 μg/cm²/h).     

Preparation,characterization and pharmacological evaluation of tolterodine hydrogels for the treatment of overactive bladder

In this study, transdermal gel formulations for tolterodine were developed to investigate the effects of gel matrix and chemical enhancers on drug skin permeation from tolterodine hydrogels. In vitro permeation studies of tolterodine through excised mouse skin were carried out using Franz-type diffusion cells. In the optimum gel formulation, Carbopol 940 was selected as the gel matrix. Compared to gels without enhancer, tolterodine hydrogels with N-methyl pyrrolidone (NMP) showed significant enhancing effect on transdermal permeation of tolterodine (p < 0.05). The results of in vitro percutaneous delivery experiment showed that the relationship of the steady accumulative percutaneous amount (Q, μg cm⁻²) of tolterodine hydrogels and time was Q_4–12h = 770.19t^1/2 − 966.99. Tolterodine permeated at the steady-state speed of 770.19 μg cm⁻² h⁻¹ and its release coincided with Higuchi Equation. The pharmacokinetic properties of the optimized tolterodine formulation were studied in rabbits. The absolute bioavailability of tolterodine was 11.47%. Since the absence of hepatic first-pass metabolism, only a single active compound-tolterodine was detected in the plasma. A skin irritation study was also carried out on rabbits, and the results showed tolterodine hydrogels had no skin irritation. In the pharmacodynamic study, the significant effects of tolterodine hydrogels on the inhibition of pilocarpine-induced rat urinary bladder contraction were last to 12 h, indicating that tolterodine hydrogels could produce prolonged pharmacological responses. In conclusion, tolterodine hydrogels were formulated successfully using Carbopol 940 and NMP and these results helped in finding the optimum formulation for percutaneous drug release. It is quite evident that tolterodine hydrogels may offer a possibility to avoid the first-pass effect, resulting in a single active compound of tolterodine in plasma, which may profit on the patient under the dose control and the reduction of potential adverse effect from two active compounds in the body.     

Transdermal Iontophoretic Delivery of Propofol: A General Anaesthetic in the Form of its Phosphate Salt

The main objective of this study was to investigate the feasibility of delivery of propofol phosphate (PP), a prodrug of propofol, via transdermal route using iontophoresis in combination with chemical permeation enhancers (CPEs). PP, a prodrug, was synthesized and its structure was characterized. In vitro passive and iontophoretic drug transport studies were carried out using Franz diffusion cell across freshly excised hairless rat skin at different concentrations of PP in combination with CPE. Among all the CPEs screened, 0.1% sodium dodecyl sulfate (SDS) increased the passive transdermal flux to 13.43 ± 0.73 μg/(cm² h) from 8.52 ± 0.82 μg/(cm² h) (control). Cathodal iontophoresis in combination with 0.1% SDS synergistically enhanced the flux [249.24 ± 6.12μg/(cm² h)] of PP. The Pharmacokinetic studies were performed in rat model to assess the feasibility of transdermal delivery of PP. The amount of propofol present in plasma samples in control group (passive) was below the detectable levels at all the time points during the study. The plasma concentration—time profile of iontophoresis group of rats was fit to a noncompartmental model and the pharmacokinetic parameters were calculated. These studies suggest the plausibility of achieving therapeutically relevant levels of propofol when delivered via transdermal route by combining iontophoresis with CPE.     

Terbutaline Transdermal Delivery: Preformulation Studies and Limitations of In-vitro Predictive Parameters

A transdermal dosage form of terbutaline may be useful to prevent nocturnal wheezing by providing prolonged duration of action. It will also improve patient compliance and bioavailability. Controlled input of the drug would be an additional advantage as this will reduce the intersubject variablity. Preformulation studies were conducted to determine the feasibility of a transdermal dosage form of terbutaline. The drug solubility in propylene glycol was 6.3 mg mL^?1. The apparent partition coefficient (n-octanol/deionized-water, pH 6.5) of terbutaline was 0.03. A pH-partition coefficient (octanol/buffer) profile indicated that the partition coefficient values were 0.02, 0.05 and 04 in buffers of pH 3, 7.4 and 9, respectively. The required drug flux through the human skin to attain therapeutic concentrations in the blood was calculated to be 3.3 μg cm^?2 h^?1 for a 10-cm² transdermal delivery system. Rabbit, guinea-pig and human skin was tested as the penetration barrier using modified Franz diffusion cells. Terbutaline flux values through the rabbit and guinea-pig skin were 8.3 and 7.7 μg cm^?2 h^?1, respectively. The flux through human full-thickness skin and human epidermis were 0.6 and 3.6 μg cm^?2 h^?1. Azone (3% w/v), a skin penetration enhancer, significantly increased the drug flux through all the membranes tested. Based on these studies, transdermal delivery of terbutaline appears to be promising.     

Effect of fatty acids on the transdermal delivery of donepezil: in vitro and in vivo evaluation

The effect of fatty acids on the skin permeation of donepezil base (DPB) and its hydrochloride salt (DPH) were studied in vitro using hairless mouse and human cadaver skin. DPB and DPH were solubilized in propylene glycol (PG) containing 1% (w/v) fatty acid, after which the in vitro permeation through hairless mouse skin and human cadaver skin were evaluated using Keshary-Chien diffusion cells. The optimized formulation obtained from the in vitro study was then tested in rats for an in vivo pharmacokinetic study. The relative in vitro skin permeation rate of donepezil (DP) through the hairless mouse skin showed a parabolic relationship with increased carbon length of the fatty acid enhancers. Among the fatty acids tested, oleic acid for DPB and palmitoleic acid for DPH showed the highest enhancing effect, respectively. Both the permeation rates of DPB and DPH evaluated in human cadaver skin were in good correlation with those in hairless mouse skin, regardless of the presence of fatty acids. This suggests that the mouse skin model serves as a useful in vitro system that satisfactorily represents the characteristics of the human skin. Moreover, based on the in vitro results, the optimal formulation that could maintain the human plasma concentration of 50 ng/mL was determined to be 10mg DP with 1% (w/v) enhancer. When the DP transdermal formulations were applied to the abdominal skin of rats (2.14 cm(2)), the C(ss) was maintained for 48 h, among which the highest value of 52.21 ± 2.09 ng/mL was achieved with the DPB formulation using oleic acid. These results showed that fatty acids could enhance the transdermal delivery of DP and suggested the feasibility of developing a novel transdermal delivery system for clinical use.     

Transdermal delivery of low molecular weight heparin loaded in flexible liposomes with bioavailability enhancement: comparison with ethosomes

Low molecular weight heparin (LMWH)-loaded flexible liposomes (flexosomes) were formulated for transdermal delivery, and their physicochemical and pharmacokinetic parameters were compared with LMWH-loaded ethosomes. Flexosomes had similar particle size compared with ethosomes, but their deformability was higher than that of ethosomes (76.7% vs. 46.8%). In vitro, flexosomes demonstrated 2.6-fold higher permeability coefficient than ethosomes. In comparison to LMWH aqueous solution, skin deposition of flexosome increased 3.2-fold, while that of ethosome increased only 2.0-fold. In vivo, after the topical application of flexosome to hairless mouse, [anti-Xa]_max was 1.11?IU/mL, while ethosomes showed only 0.32?IU/mL. Moreover, AUC_0–24?h of flexosomes was 2.5-fold higher than ethosomes. In conclusion, the enhanced skin permeation and bioavailability of LMWH can be achieved with flexosomes in comparison with ethosomes. The LMWH transdermal delivery via flexosomes has the potential to replace the parenteral dosage forms for the treatment of venous thromboembolism, pulmonary embolism and cardiovascular events.     

Topical delivery of cyclosporin A: an in vitro study using monoolein as a penetration enhancer.

Topical delivery of cyclosporin A (CysA) is of great interest for the treatment of autoimmune skin disorders, but it is frequently ineffective due to poor drug penetration in the skin. The present study was aimed at investigating whether the presence of monoolein (a lipidic penetration enhancer) in a preparation of propylene glycol can improve CysA delivery to the skin. CysA was incorporated in a propylene glycol preparation containing 5-70% (w/w) of monoolein. The topical (to the skin) and transdermal (across the skin) delivery of CysA were evaluated in vitro using porcine ear skin mounted in a Franz diffusion cell. CysA was quantified by UV-HPLC. At 5%, monoolein increased only the transdermal delivery of CysA. At 10%, it increased both topical and transdermal delivery. When the concentration of monoolein was further increased (20-70% w/w), an interesting phenomenon was observed: the topical delivery of CysA was still elevated but its transdermal delivery was substantially reduced. It was concluded that monoolein (in propylene glycol formulations) can promote the topical delivery of CysA, with reduced transdermal delivery.     

渗透促进剂对胰岛素体外经皮离子导入渗透性的影响

本文考察了某些渗透促进剂如月桂氮Zhuo酮（AZ）、油酸（OA）、泊洛沙姆（POL）和丙二醇（PG）等对胰岛素体外经皮离子导入渗透性的影响。结果表明AZ对离子导入具有协同作用，PG能够增强这种作用，三者并用对胰岛素的经皮渗透具有特别显著的促渗效果。5％AZ／PG与离子导入并用后，较单独离子导入处理组的促渗因子为2.75。OA不能增强离子导入的作用，离子导入与某些渗透促进剂并用为胰岛素等大分子多肽类药物的透皮给药提供了新的思路和可能。     

Utility of Nanosized Microemulsion for Transdermal Delivery of Tolterodine Tartrate: Ex-Vivo Permeation and In-Vivo Pharmacokinetic Studies

Purpose

The aim of this work was to investigate the feasibility of using nanosized microemulsion for transdermal delivery of tolterodine tartrate.

Methods

The effect of three microemulsions formed by Labrasol: Plurol (3:1), isopropyl myristate and water on the permeation of tolterodine through miniature pig skin was studied in vitro using Franz diffusion cell. For comparison purpose, the effect of different vehicles on the permeation was also studied. Drug pharmacokinetics was studied after transdermal application to human volunteers compared to the commercial oral dosage form using a newly developed LC-MS/MS assay.

Results

The vehicle PEG 400:Phosphate buffer pH 7.4 in the ratio of 1:1 significantly enhanced tolterodine permeation across pig skin. The microemulsion system (ME3) containing the highest amount of water (50%) significantly enhanced permeation with Q₂₄ of 0.746 mg.cm^?2. In contrast to oral delivery, a sustained activity was observed over a period of 72 h after transdermal application of this microemulsion to human volunteers with significant lower C_max (1.06 ng/ml), delayed T_max (3.17 h) and higher MRT value (147.82 h) (p?<?0.05).

Conclusion

This sustained activity was due to the controlled release of drug into the systemic circulation with expected increase in the patient compliance and prevention of nocturnal enuresis.     

In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic

Objectives The feasibility of transdermal delivery of tramadol, a centrally acting analgesic, by anodal iontophoresis using Ag/AgCl electrodes was investigated in vitro and in vivo. Methods To examine the effect of species variation and current strength on skin permeability of tramadol, in‐vitro skin permeation studies were performed using porcine ear skin, guinea‐pig abdominal skin and hairless mouse abdominal skin as the membrane. In an in‐vivo pharmacokinetic study, an iontophoretic patch system was applied to the abdominal skin of conscious guinea pigs with a constant current supply (250 µA/cm²) for 6 h. An intravenous injection group to determine the pharmacokinetic parameters for estimation of the transdermal absorption rate in guinea pigs was also included. Key findings The in‐vitro steady‐state skin permeation flux of tramadol current‐dependently increased without significant differences among the three different skin types. In the in‐vivo pharmacokinetic study, plasma concentrations of tramadol steadily increased and reached steady state (336 ng/ml) 3 h after initiation of current supply, and the in‐vivo steady‐state transdermal absorption rate was 499 µg/cm² per h as calculated by a constrained numeric deconvolution method. Conclusions The present study reveals that anodal iontophoresis provides current‐controlled transdermal delivery of tramadol without significant interspecies differences, and enables the delivery of therapeutic amounts of tramadol.     

Transdermal skin delivery: predictions for humans from in vivo, ex vivo and animal models

The assessment of percutaneous permeation of molecules is one of the main steps in the initial design and later in the evaluation of dermal or transdermal drug delivery systems. The literature reports numerous ex vivo, in vitro and in vivo models used to determine drug skin permeation profiles and kinetic parameters, some studies focusing on the correlation of the data obtained using these models with the dermal/transdermal absorption in humans. This paper reviews work from in vitro permeation studies to clinical performance, presenting various experimental models used in dermal/transdermal research, including the use of excised human or animal skin, cultured skin equivalents and animals. Studies focusing on transdermal absorption of a series of drug molecules and various delivery systems as well as mathematical models for skin absorption are reviewed.     

难溶性多西紫杉醇的溶解微针制备及体外评价

目的:制备一种用于透皮给药的负载多西紫杉醇(DTX)的溶解微针,并进行体外评价。方法:考察不同材料及配方制备DTX溶解微针(DTX-MN),通过外观和力学性能指标对微针进行表征,测定微针针头载药量。使用猪皮肤考察微针溶解性能。剥离小鼠腹部皮肤,进行体外透皮吸收研究,初步考察DTX-MN给药后的皮肤药代动力学。结果:成功制备了针头完整、力学性能良好的DTX-MN,最佳工艺得到的微针针头载药量为(14.81±4.20)μg (n=5),微针能完整插入皮肤穿透角质层屏障,且在10 min内完全溶解。体外透皮实验显示,DTX-MN的初始透皮速率和累积透皮通量都高于药物溶液组,相比溶液组,DTX-MN在24 h后累积渗透量提高了3.27倍,其释放机制符合Fickian扩散。结论:制备的DTX-MN有良好的穿刺皮肤的性能,能够显著促进DTX的透皮递送,该类微针有望促进DTX的浅表皮肤递送,具有潜在的临床应用价值。     

Design and dermatokinetic appraisal of lornoxicam-loaded ultrafine self-nanoemulsion hydrogel for the management of inflammation: In vitro and in vivo studies

The present study aimed to evaluate the impact of ultrafine nanoemulsions on the transdermal delivery of lornoxicam (LOR) for management of the inflammation. The transdermal administration of LORNE could increase the efficacy of LOR with a reduction in side effects. Merging the beneficial properties of ultrafine nanoemulsions and their components (penetration enhancers) can lead to good solubilization, a small droplet size, and more effective LOR carriers. Therefore, this study aims to develop and evaluate the potential use of ultrafine nanoemulsions of LOR (LORNE) to elucidate their skin targeting for the treatment of inflammation. Based on solubility and pseudo ternary phase diagram tests, ultrafine LORNE composed of Labrafil M 2125 CS, Cremophor RH40, and Transcutol HP to deliver LOR was developed and characterized for its physicochemical properties, emulsification, and in vitro release. The selected LORNE was incorporated into carbopol gel (LORNE-Gel) and examined for ex vivo skin permeation, retention, dermatokinetics, anti-inflammatory efficacy, and skin irritation. The selected LORNE12-Gel could improve skin permeation, retention, and dermatokinetic results significantly (p < 0.05) with enhanced C_{Skin max} and AUC_0-48h compared to LOR-Gel. Moreover, LORNE12-Gel showed a remarkable anti-inflammatory effect compared to LOR-Gel after topical application. No signs of skin irritation were observed following treatment, indicating the safety of LORNE12-Gel. Thus, this study demonstrated that LOR-loaded LORNE12-Gel could be promising as an efficient transdermal nanocarrier for an anti-inflammatory alternative.     

Enhancement of transdermal delivery of progesterone using medium-chain mono and diglycerides as skin penetration enhancers

We evaluated whether medium-chain mono and diglycerides (MCG) can be utilized to optimize the transdermal delivery of progesterone (PGT). MCG was studied at 10–70% (w/w) in propylene glycol (a polar solvent) or Myvacet oil (nonpolar solvent); PGT was used at 1% (w/w). The topical (to the skin) and transdermal (across the skin) delivery of PGT were evaluated in vitro using porcine ear skin. When incorporated in propylene glycol, MCG at 10% enhanced the topical and transdermal delivery of PGT by 2.5- and 7-fold, respectively. At 20–50%, topical delivery was further enhanced while transdermal delivery gradually returned towards baseline. At 70%, MCG enhanced neither the delivery to viable skin nor the transdermal delivery of PGT. Similar concentration-dependent effects were observed when MCG was incorporated in Myvacet oil, but their magnitudes were 2- to 3-fold smaller. The relative safety of MCG was assessed in cultured fibroblasts and compared to propylene glycol (regarded as safe) and sodium lauryl sulfate (moderate-to-severe irritant). Both MCG and propylene glycol were substantially less cytotoxic than sodium lauryl sulfate. We conclude that formulations containing 10% MCG in propylene glycol may be a simple and safe method to improve the transdermal delivery of progesterone and promote its use in hormone replacement therapy.     

Glycine reduces novelty- and methamphetamine-induced locomotor activity in neonatal ventral hippocampal damaged rats.

The use of neonatal ventral hippocampal nVH lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. To examine the effect of glycine (GLY) in this animal model, we compared the effects of GLY (0.8 and 1.6 g/kg, IP) on locomotor activity induced by a novel environment (NOVEL) and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. Compared with sham rats, GLY significantly reduced NOVEL- and MAP-induced locomotor activity in lesioned rats (p <.001 and p <.05, respectively). It is suggested that GLY attenuated nVH-induced hyperactivity, and that this effect was evident both in the presence and absence of MAP. The nVH lesions may result in a form of hyperactivity that differs from normal locomotion in the degree to which it is highly sensitive to regulation by GLY.     

Effect of permeation enhancers on transdermal delivery of fluoxetine: In vitro and in vivo evaluation

The aim of this study was to investigate the feasibility of transdermal fluoxetine (FX) delivery. The effects of chemical forms (base or salt) and permeation enhancers on in vitro skin permeation of FX were assessed using hairless mouse, rat and human cadaver skin. The optimized formulations from the in vitro studies were then evaluated in an in vivo pharmacokinetic study in rats. The in vitro skin permeation studies suggested that the FX base (FXB) and isopropyl myristate (IPM)–limonene mixture could be suitable for transdermal delivery of FX. The permeation parameters of FX through human cadaver skin were well correlated with that through hairless mouse and rat skin, suggesting that these animal models can be used for predicting the permeability of FX through human skin. After transdermal administration of FX with IPM or the IPM–limonene mixture to rats, the mean steady-state plasma concentration (C_ss) was 66.20 or 77.55 ng/mL, respectively, which was maintained over 36 h and had a good correlation with the predicted C_ss from the in vitro data. These in vitro and in vivo data demonstrated that permeation enhancers could be a potential strategy for transdermal delivery of FX.     

Design and in vivo evaluation of an indapamide transdermal patch

The aim of the present study was to develop and evaluate a novel drug-in-adhesive transdermal patch system for indapamide. Initial in vitro experiments were conducted to optimize formulation parameters prior to transdermal delivery in rats. The effects of the type of adhesive and the content of permeation enhancers on indapamide transport across excised rat skin were evaluated. The results indicated that DURO-TAK^® adhesive 87-2852 is a suitable and compatible polymer for the development of transdermal drug delivery systems for indapamide. The final formulation contained 4% N-dodecylazepan-2-one, 6% l-menthol and 3% isopropyl myristate. For in vivo studies patch systems were administered transdermally to rats while orally administered indapamide in suspension was used as a control. The PK parameters, such as the maximum blood concentration (C_max), time to reach the peak blood concentration (T_max), mean residence time (MRT), area under the curve (AUC_0–t) and terminal elimination half-life (T_1/2) were significantly (p < 0.05) different following transdermal administration compared with oral administration. In contrast to oral delivery, a sustained activity was observed over a period of 48 h after transdermal administration. This sustained activity was due to the controlled release of drug into the systemic circulation following transdermal administration.     

Novel sugar esters proniosomes for transdermal delivery of vinpocetine: Preclinical and clinical studies

Vinpocetine (Vin) existing oral formulations suffer poor bioavailability (∼7%) since Vin undergoes a marked first-pass effect (∼75%) and its absorption is dissolution rate-limited. In this study, a novel sustained release proniosomal system was designed using sugar esters (SEs) as non-ionic surfactants in which proniosomes were converted to niosomes upon skin water hydration following topical application under occlusive conditions. Different in vitro aspects (encapsulation efficiency, vesicle size and shape, effect of occlusion, in vitro release, skin permeation and stability) were studied leading to an optimized formula that was assessed clinically for transdermal pharmacokinetics and skin irritation.All formulae exhibited high entrapment efficiencies, regardless of the surfactant HLB. Vesicle size analysis showed that all vesicles were in the range from 0.63 μm to 2.52 μm which favored efficient transdermal delivery. The extent of drug permeation through the skin from the optimized formula - containing laurate SE with shorter fatty acid chain length and high HLB - was quite high (91%) after 48 h under occlusive conditions. The extent of absorption of Vin from proniosomes was larger when compared to the oral tablet with a relative bioavailability (F_rel) of 206%. Histopathological evaluation revealed only moderate skin irritation when using SEs compared to skin inflammation when using Tween 80. Sugar esters proniosomes may be a promising carrier for vinpocetine, especially due to their simple scaling up and their ability to control drug release.