Screening of Venlafaxine Hydrochloride for Transdermal Delivery: Passive Diffusion and Iontophoresis

The objective of the study was to investigate in vitro transdermal delivery of venlafaxine hydrochloride across the pigskin by passive diffusion and iontophoresis. For passive diffusion, experiments were carried out in Franz diffusion cell whereas for iontophoretic permeation, the diffusion cell was modified to contain both the donor and return electrode on the same side of skin. Anodal iontophoresis was carried out using a current density of 0.5 mA/cm². Donor concentrations used were 585.5 mg/ml (saturated solution) and 100 mg/ml. Experiments initially performed to determine the transport efficiency of venlafaxine ions showed promising results. Iontophoresis increased the permeation rate at both concentration levels over their passive counterparts (P < 0.01), but surprisingly higher steady-state flux was obtained from lower donor drug load (P < 0.01). The favorable pH of the unsaturated solutions is suggested to be the cause for this effect. Mild synergistic effect was observed when iontophoresis was carried out incorporating peppermint oil in the donor but the same was not found in passive diffusion. Highest steady-state flux obtained in the experiment was 3.279 μmol/cm²/h when peppermint oil (0.1%) was included in the donor. As the maintenance requirement of venlafaxine hydrochloride is approximately 9.956 μmol/h, the results suggested that the drug is a promising candidate for iontophoretic delivery.     

Lateral Drug Diffusion in Human Nails

The main objective of the current work is to demonstrate the process of passive lateral diffusion in the human nail plate and its effect on the passive transungual permeation of antifungal drug ciclopirox olamine (CPO). A water soluble dye, methyl red sodium salt (MR) was used to visualize the process of lateral diffusion using a novel suspended nail experiment. The decline in concentration of CPO correlates with that of concentration of MR from the proximal to the distal end of the nail in suspended nail study. Three toenails each were trimmed to 5 mm × 5 mm (25 mm²), 7 mm × 7 mm (49 mm²), and 9 mm × 9 mm (81 mm²) to study the extent and effect of lateral diffusion of the CPO on its in vitro transungual permeation. The permeation flux of CPO decreased as the surface area of the toenail increased. There was a positive correlation between the concentrations of CPO and MR in the area of application and in the peripheral area of the toenails of the three surface areas, confirming the findings in the suspended nail experiment. Profound lateral diffusion of CPO was demonstrated and shown to reduce the in vitro passive transungual drug permeation and prolong the lag-time in human toenails. The study data implies that during passive in vitro transungual permeation experiments, the peripheral nail around the area of drug application has to be kept to a minimum, in order to get reliable data which mimics the in vivo situation.KEY WORDS: ciclopirox olamine, lateral diffusion, passive, topical, transungual     

Optimized Ciclopirox-Based Eudragit RLPO Nail Lacquer: Effect of Endopeptidase Enzyme as Permeation Enhancer on Transungual Drug Delivery and Efficiency Against Onychomycosis

The aims of our investigation were to develop and optimize ciclopirox (CPX) nail lacquer using nonbiodegradable Eudragit RLPO (E-RLPO) as a film former and to assess its penetration efficiency across the human nail plate. Preliminary trials such as hydration enhancement factor (HEF), a retained drug in the nail plate, and SEM were studied to select the optimized permeation enhancer to be incorporated in the optimized lacquer formulation. A 3³ full factorial design was built up to study the effect of three different factors, concentration of E-RLPO (10, 20, and 30%), Tween 80 (0.25, 0.5, and 1%), and triacetin (0, 10, and 30% of polymer weight). The studied responses were the drying time, water resistance, viscosity, and drug release up to 4 h. An ex vivo permeation study for the optimized formulations was carried out. The preliminary study aided the selection of 5% papain (endopeptidase enzyme) as a penetration enhancer; it showed the highest HEF of 15.27%, the highest amount of drug retained in the nail plate (886.2 μg/g). An ex vivo permeation study guided the selection of F4B (flux value of 3.79 μg/cm²/h) as optimized formulation. The optimized lacquer formula showed threefold increases in the permeation than the marketed CPX lacquer (Batrafen®). Confocal laser scanning microscopy revealed the higher intensity of the Rhodamine B dye across the nail plate in the case of the formula containing papain than the marketed formula without papain. Conclusively, an efficient and stable nail lacquer was developed for potential transungual delivery of CPX to target the drug to the nail bed and ensure efficiency against onychomycosis.     

A Preformulation Strategy for the Selection of Penetration Enhancers for a Transungual Formulation

Onychomycosis is associated with the cutaneous fungal infection of the nail and the nail folds (skin surrounding the nail). It is therefore important to target drug delivery into the nail folds along with nail plate and the nail bed. Systematic and strategic selection of the penetration enhancers specific for the skin and the nail is discussed. Twelve penetration enhancers were screened for their ability to improve solubility, in vitro nail penetration, in vitro skin permeation, and in vitro skin penetration of the antifungal drug ciclopirox olamine. In contrast to transdermal drug delivery, the main selection criteria for skin penetration enhancer in topical drug delivery were increased drug accumulation in the epidermis and minimal permeation across the skin. Thiourea improved the solubility and nail penetration of ciclopirox olamine. It also showed enhancement in the transungual diffusion of the drug. Propylene glycol showed a 12-fold increase in solubility and 3-fold increase in epidermal accumulation of ciclopirox olamine, while minimizing the transdermal movement of the drug. Thiourea was the selected nail permeation enhancer and propylene glycol was the selected skin penetration enhancer of ciclopirox olamine. A combination of the selected enhancers was also explored for its effect on drug delivery to the nail and nail folds. The enhancer combination reduced the penetration of ciclopirox in the skin and also the permeation through the nail. The proposed preformulation strategy helps to select appropriate enhancers for optimum topical delivery and paves way towards an efficient topical formulation for passive transungual drug delivery.     

甲真菌病体外模型研究

目的 构建一个简单、经济的新的甲真菌病体外模型.方法 制备猪甲板,在其腹侧面中央黏贴一个“O”型圈,将受试菌液加入“O”型圈内,将甲板放置培养皿中培养,用大体观察及组织病理的方法动态观察不同真菌侵袭甲板的情况.结果 用猪甲板制备甲真菌病体外模型,通过该模型观察了红色毛癣菌、须癣毛癣菌以及白念珠菌穿透甲板的能力.通过组织病理学方法观察到了真菌动态穿透甲板的过程.结论 该模型适用于评估真菌对甲板的致病作用.     

Enhancement of iontophoretic transport of diphenhydramine hydrochloride thermosensitive gel by optimization of pH, polymer concentration, electrode design, and pulse rate

The purpose of the present study was to explore the passive and electrically assisted transdermal transport of diphenhydramine hydrochloride (DPH) by iontophoresis. For better bioavailability, better patient compliance, and enhanced delivery of DPH, an iontophoretic drug delivery system of a thermosensitive DPH gel was formulated using Lutrol F-127. The study was conducted using silver-silver chloride electrodes across hairless pig skin. The effects of pH, polymer concentration, electrode design, and pulse rate on the DPH permeation were investigated. The relationship between temperature, viscosity, and conductance of DPH was correlated using conductometry. Iontophoretic transport of DPH was found to increase with a decrease in the pH of the medium and an increase in the surface area of the electrode. Viscosity measurements and flux calculations indicated the suitability of the Lutrol gel for transdermal iontophoretic delivery of DPH. Anodal pulsed iontophoresis with disc electrode significantly increased the DPH skin permeation as compared with the passive controls.     

Column Flushing of Phenanthrene and Copper (II) Co-Contaminants from Sandy Soil Using Tween 80 and Citric Acid

The clean-up of soils co-contaminated with heavy metals and organic compounds is a contemporary issue of remediation efforts. Column flushing was conducted to investigate the performance of nonionic surfactant and/or organic acid solutions, 4000 mg/L Tween 80 (TW80), and/or 0.04 mol/L citric acid (CA), to enhance the simultaneous removal of phenanthrene and copper (II) from the co-contaminated sandy soil. The flushing effects were compared when TW80, CA, TW80 after CA (CA/TW80), CA after TW80 (TW80/CA), and a mixture of TW80 and CA (TW80-CA) were used as flushing agents. The maximum concentrations of phenanthrene in effluent solutions occurred at 3.3, 4.7, 5.3, and 15.3 h during TW80, TW80/CA, TW80-CA, and CA/TW80 flushing and those of copper (II) at 2.7, 3.3, 3.3, and 14.0 h during CA, CA/TW80, TW80-CA, and TW80/CA flushing, respectively. Phenanthrene was mainly desorbed through partitioning into TW80 micelles in aqueous phase while copper (II) was effectively removed through complexation with CA. The removal efficiencies were up to 81.5%, 5.9%, 99.9%, 91.6%, and 99.8% for phenanthrene, and 0.1%, 76.7%, 85.7%, 78.1%, and 84.4% for copper (II) by TW80, CA, TW80/CA, TW80-CA, and CA/TW80. However, it took a long time to use TW80/CA and CA/TW80 to clean phenanthrene and copper (II) efficiently. The overall removal efficiencies of contaminants in the soil column increased with flushing time in the Sigmoidal Model. The results indicated that a combination of TW80 and CA has potential for in situ clean-up of heavy metals and polycyclic aromatic hydrocarbons (PAHs) from co-contaminated soils.     

Design and development of ethosomal transdermal drug delivery system of valsartan with preclinical assessment in Wistar albino rats

Abstract

Valsartan (VLT) is a highly selective and orally active antihypertensive drug. However, its oral administration is associated with drawbacks like low bioavailability. The objective of this study was to design and develop a transdermal delivery system for VLT using ethosomal carriers to investigate their enhanced transdermal delivery potential. VLT ethosomes were prepared by cold method. VLT ethosomes were characterized by scanning electron microscopy. The prepared ethanolic liposomes were characterized to be spherical having low polydispersity of nano-size range with good entrapment efficiency. ETC5 ethosomal suspension with 4% of phospholipon 90H and 40% of ethanol was found to have highest entrapment efficiency, i.e. 80.230?±?0.8748%. The permeation study of ethosomes was evaluated by ex vivo diffusion study through rat abdominal skin using Franz’s diffusion cells and ETC5 ethosomal suspension was found to have highest permeation with flux of 92.819?±?1.539?µg/cm²/h, when compared to the permeation profiles of drug solutions either in water or in a water–ethanol mixture. Transdermal application of ethosomal VLT on Wistar rats showed better and prolonged antihypertensive activity in comparison to orally administered VLT suspension by virtue of transdermal permeation through Wistar rat skin. Histopathological study of skin applied with ETC5 showed intercellular permeation across skin by dissolving intercellular lipids in epidermis without causing any rigorous changes in the skin cellular structure. In conclusion, ethosomes enabled the transdermal permeation of VLT, which amply proves its superiority over oral administration for antihypertensive treatment.     

Crossflow filtration of baker's yeast with periodical stopping of permeation flow and bubbling

The periodical stopping of permeation flow was applied to increase the permeation flux in crossflow filtration of commercially available baker's yeast cell suspension. The permeation flux after 3 h filtration in the crossflow filtration increased to 8 x 10(-5) m(3) /m(2) s (290 L/m(2) h) from 2 x 10(-5) m(3)/m(2) s (72 L/m(2) h) by applying the periodical stopping of permeation. Introduction of air bubbles during the stopping period of permeation further increased the flux.(c) John Wiley & Sons, Inc.     

Passive and iontophoretic transport enhancement of insulin through porcine epidermis by depilatories: Permeability and fourier transform infrared spectroscopy studies

The effect of thioglycolate-based depilatory lotions was studied on the in vitro passive and iontophoretic permeability of insulin through porcine epidermis and biophysical changes in the stratum corneum (SC) lipids and proteins. The porcine epidermis and Franz diffusion cells modified for iontophoresis were used for the in vitro transport studies. Cathodal iontophoresis was performed at 0.2 mA/cm² current density. Resistance of the control- and depilatory-lotion-treated epidermis was determined according to Ohmslaw. Biophysical changes were studied on porcine SC before (control) and after treatment with the depilatory lotions using Fourier transform infrared (FT-IR) spectroscopy. Asymmetric (∼2915 cm⁻¹) and symmetric (∼2848 cm⁻¹) Carbon-Hydrogen (C-H) stretching absorbances were studied to estimate the extent of lipid extraction. Fourier self-deconvolution and second derivative procedures were applied to amide I band (1700–1600 cm⁻¹) in order to estimate quantitatively the changes in the secondary structure of the SC protein. The passive permeability of insulin was significantly (P<.05) increased through depilatory-lotion-treated (ie, Better Off, Marzena, and Sally Hansen) epidermis in comparison to control. Iontophoresis significantly enhanced (P<.05) the permeability of insulin through depilatory-pretreated epidermis in comparison with the control epidermis. Further, we were able to achieve the desired flux of insulin (5.25 U/cm²/d) through Better Off-treated epidermis using 0.2 mA/cm² current density and 100 U/mL donor concentration of insulin. The SC treated with depilatory lotions showed a decrease in peak areas of C-H stretching absorbances in comparison with untreated SC. Depilatory lotion treatment also decreased (P<.05) the epidermal resistance in comparison with the control epidermis. The decrease in the α-helix conformation and the increase in the random and turn structures were observed in the SC proteins due to depilatory lotion treatment. The changes in the secondary structure of proteins and lipid extraction from the SC are suggested as the cause of the decrease in the epidermal resistance and the increase in the passive and iontophoretic permeability of insulin through depilatory-pretreated epidermis in comparison with the control epidermis.     

The automated, accurate and reproducible determination of steady-state permeation parameters from percutaneous permeation data

Procedures for the in vitro determination of percutaneous permeation with Franz diffusion cells are widely accepted. However, the calculation of relevant endpoints, such as the steady-state flux (J) and the permeation coefficient (P(app)), still depends on visual data inspection or an approximation of the steady-state flux as the maximum observed absorption rate. As both these approaches must be considered inappropriate, an automated and reproducible algorithm to analyse permeation data is presented. The method detects both lag-times and non-linear data resulting from substance accumulation in the acceptor compartment of static diffusion cells. It was evaluated by using simulated data, and data from experiments with caffeine and testosterone on bovine udder skin and human reconstituted epidermis (SkinEthic), which represent model barriers with high and low barrier strengths, respectively. It was shown that the algorithm is a suitable method for the identification of steady-state ranges in permeation data. If used on data generated with appropriate experimental approaches, it is a reproducible and time-saving alternative to the visual analysis of diffusion data.     

Application of Microneedle Arrays for Enhancement of Transdermal Permeation of Insulin: <Emphasis Type="Italic">In Vitro</Emphasis> Experiments,Scaling Analyses and Numerical Simulations

The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses were done using dimensionless parameters like concentration of drug (C _t/C _s), thickness (h/L) and surface area of the skin (S _a/L ²). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN-treated skin and experimental parameters like passive diffusion coefficient. A 1.6-fold increase in transdermal flux and 1.9-fold decrease in lag time values were observed with 1.5 mm MN when compared with passive studies. Good correlation (R ²?>?0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f ₂?≥?50). Insulin permeation significantly increased with increase in donor concentration and MN length (p?<?0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans.     

Differential permeation of propranolol enantiomers across human skin in vitro from formulations containing an enantioselective excipient.

This work tested the hypothesis that a stereospecific topical formulation could be used to engineer differential permeation rates for each enantiomer of an applied racemate across human skin in vitro. Racemic and enantiomerically pure R or S propranolol HCI were formulated with cellulose tris(3,5-dimethyl phenyl carbamate) (CDMPC) and applied to excised human skin using side-by-side Franz-type diffusion cells. When the pure enantiomers were used, there was a marked difference between the penetration rates of R and S propranolol (flux ratio: 2.06; P = 0.04). When racemic propranolol was used, the difference was reduced, although still statistically significant (flux ratio: 1.2; P = 0.08), particularly in view of the differential activities of the two enantiomers. Control experiments, in which no CDMPC was present, produced equal permeation rates. The results can be rationalised in terms of differential adsorption onto CDMPC within the vehicle, whereby S-propranolol is preferentially bound relative to R-propranolol. This causes an imbalance in the apparent donor phase concentrations that (in accordance with Fickian diffusion laws and thermodynamic activity) gives rise to differences in permeation rates. The diminished differential observed when the racemate was used, rather than individual enantiomers, is less easily rationalised. In this work, it was the permeation of the eutomer (S-propranolol) that was retarded, although the general principle of stereoselectively retarded skin permeation has been established.     

Preparation and <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation of a New Fentanyl Patch Based on Functional and Non-functional Pressure Sensitive Adhesives

In this study, some single-layer and double-layer transdermal drug delivery systems (TDDSs) with different functional and non-functional acrylic pressure-sensitive adhesives (PSAs) were prepared. For this purpose, fentanyl as a drug was used. The effects of PSAs type, single-layer and double-layer TDDSs on skin permeation and in vitro drug release from devices were evaluated using a hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices such as peel strength and tack values were obtained as well. It was found that TDDS with –COOH functional PSA showed the lowest steady-state flux. Double-layer TDDS displayed a constant flux up to 72 h. In double- and single-layer devices after 1 and 3 h, respectively, drug release followed Higuchi’s kinetic model. Formulations with the highest percentage of –COOH functional PSA have displayed the lowest flux. The double-layer TDDSs with non-functional PSA demonstrated the suitable skin permeation rate close to Duragesic® TDDS and suitable adhesion properties.     

Effect of magnetic field on the ultrafiltration of bovine serum albumin

This work evaluates the effects of a static magnetic field on the permeation of bovine serum albumin (BSA) in a tangential ultrafiltration membrane module. Experimental tests were carried out at different pHs using a poly(sulfone) membrane with molecular weight cut off of 60 kDa under the influence of a 0.4 T neodymium-iron-boron magnetic field. Results showed an increase in the permeate flux of water after the cleaning procedures of the new and reused membranes in the presence of the magnetic field. The elusive mechanism of magnetic memory is also shown to take place for the water fluxes fully recovered after the cleaning procedures when the magnetic field was applied to the system before the permeation. When the magnetic field was applied during permeation, the water fluxes presented lower percent of recuperation after the cleaning procedures, thus suggesting that the BSA solution may have somewhat been influenced by magnetic memory.     

Comparative Pharmaceutical Evaluation of Candesartan and Candesartan Cilexetil: Physicochemical Properties, <Emphasis Type="Italic">In Vitro</Emphasis> Dissolution and <Emphasis Type="Italic">Ex Vivo In Vivo</Emphasis> Studies

The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochemical evaluation was conducted through solubility, dissolution, and stability studies; additionally, ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alkaline pH. Moreover, dissolution testing using the pharmacopeial method showed better release profile of C even in the absence of surfactant in the testing medium. Both drugs demonstrated a slight degradation in acidic pH after short-term stability. Instead, shifting to alkaline pH of 6.5 and 7.4 showed superiority of C solution stability compared to CC solution. The ex vivo permeation results demonstrated that the parent compound C has a significant (P < 0.05) enhanced permeation compared to its prodrug from CC, that agreed with in vivo results in which C suspension reached significantly (P < 0.05) higher C _max of 1.39 ± 0.59 μg/mL at T _max of 0.66 ± 0.11 h, while CC suspension reached C _max of 0.47 ± 0.22 μg/mL at T _max of 2.00 ± 0.27 h, a lag period of 40 min is needed prior to detection of any absorbed CC in plasma. Those findings are not in agreement with the previously reported rationale on the prodrug formation owing to the poor permeability of the parent compound, suggesting the possibility of marketing the parent drug candesartan for clinical use similarly to azilsartan and its prodrug.     

Fracture Toughness Properties of Three Different Biomaterials Measured by Nanoindentation

The fracture toughness of hard biomaterials, such as nacre, bovine hoof wall and beetle cuticle, is associated with fibrous or lamellar structures that deflect or stop growing cracks. Their hardness and reduced modulus were measured by using a nanoindenter in this paper. Micro/nanoscale cracks were generated by nanoindentation using a Berkovich tip. Nanoindentation of nacre and bovine hoof wall resulted in pile-up around the indent. It was found that the fracture toughness （Kc） of bovine hoof wall is the maximum, the second is nacre, and the elytra cuticle of dung beetle is the least one.     

<Emphasis Type="Italic">In vitro</Emphasis> anti-inflammatory efficacies of liposomal suspensions of acetylsalicylic acid

Egg phosphatidylcholine (EPC) liposome containing acetylsalicylic acid (ASA) (EPC/ASA liposome) was prepared by a film hydration and sonication method, and the effect of liposome on the in vitro anti-inflammatory efficacy and the in vitro skin permeation of ASA was investigated. The mean diameter of EPC liposome and EPC/ASA liposome was about 271 and 175 nm, respectively. Both of liposomes were multi-lamellar vesicles on transmission electron microscopy photos. The in vitro viability of cell (Raw264.7) treated with EPC/ASA liposome suspension was significantly lower than the viability of cell treated with ASA solution. The amount of nitrite and prostaglandin E2 produced by cell treated with EPC/ASA liposome suspension was significantly lower than the amount produced by cells treated with ASA solution, indicating EPC liposome boosted the anti-inflammatory efficacy of ASA. The amount of ASA permeated through hairless mouse skin was inappreciable for 24 h when ASA solution was applied, whereas the permeation amount markedly increased to about 185 μg/cm² for 24 h when EPC/ASA liposome suspension was applied. EPC liposome also enhanced the permeation into stratum corneum and epidermis/dermis.     

HPLC method for determination of in vitro delivery through and into porcine skin of adefovir (PMEA)

A simple HPLC/UV method for the determination of the transdermal permeation and dermal penetration of a broad-spectrum antiviral drug adefovir (PMEA) was developed. The separation was achieved on a C18 column with the mobile phase composed of 10 mM KH2PO4 and 2 mM Bu4NHSO4 at pH 6.0 and 7% acetonitrile. The method was validated with respect to selectivity, linearity (0.1-50 microg/ml), precision, accuracy, and stability. Transdermal permeation of 2% PMEA was studied in vitro using the Franz diffusion cell and porcine skin. The flux values were 1.8, 3.0, and 0.6 microg/cm2/h from aqueous donor samples at pH 3.4 and 7.4, and isopropyl myristate, respectively. The respective skin concentrations at 48 h were 294, 263, and 971 microg/g from these vehicles. These results will serve as a lead for further studies on transdermal and topical delivery of antivirals from the group of acyclic nucleoside phosphonates.     

Pharmacokinetic Evaluation of Improved Oral Bioavailability of Valsartan: Proliposomes <Emphasis Type="Italic">Versus</Emphasis> Self-Nanoemulsifying Drug Delivery System

The objective of this study was to develop proliposomes and self-nanoemulsifying drug delivery system (SNEDDS) for a poorly bioavailable drug, valsartan, and to compare their in vivo pharmacokinetics. Proliposomes were prepared by thin-film hydration method using different lipids such as soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoyl phosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. SNEDDS formulations were prepared using varying concentrations of capmul MCM, labrafil M 2125, and Tween 80. Both proliposomes and SNEDDS were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics. In vitro drug release was carried out in purified water and 0.1 N HCl using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal permeation techniques. Among the formulations, the proliposomes with drug/DMPG/cholesterol in the ratio of 1:1:0.5 and SNEDDS with capmul MCM (16.0% w/w), labrafil M 2125 (64.0% w/w), and Tween 80 (18.0% w/w) showed the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes and SNEDDS as compared to pure valsartan. Valsartan permeability across PAMPA and everted rat intestinal permeation models was significantly higher with proliposomes and SNEDDS. Following single oral administration of proliposomes and SNEDDS, a relative bioavailability of 202.36 and 196.87%, respectively, was achieved compared to pure valsartan suspension. The study results indicated that both proliposomes and SNEDDS formulations are comparable in improving the oral bioavailability of valsartan.