Essential oils from sweet basil (Ocimum basilicum) as novel enhancers to accelerate transdermal drug delivery

The purpose of this study was to evaluate the essential oils from sweet basil (Ocimum basilicum, OB) as skin permeation enhancers to promote the percutaneous absorption of drugs. The in vitro and in vivo irritancy of the essential oils was also examined. Terpenes with various carbon numbers (mono-, sesqui-, di-, and tri-) were identified in both the lower-polarity fraction (OB-1) and higher-polarity fraction (OB-2). In vitro skin permeation and deposition of indomethacin were significantly enhanced after treatment with OB essential oils. The enhancing effect of OB-1 was greater than that of OB-2 in the in vitro permeation and in vivo cutaneous microdialysis analyses as well as in the plasma concentration of indomethacin. On the other hand, the in vivo study showed that OB-2 had a greater ability to retain the drug within the skin than did OB-1. Enhancement of the skin permeation of drugs by OB essential oils might be mainly due to improvement in the partitioning of the drugs to the stratum corneum. Both in vitro cell cultures (keratinocytes and skin fibroblasts) and in vivo transepidermal water loss showed no or only negligible irritation to skin by OB essential oils.     

In vitro and in vivo evaluations of the efficacy and safety of skin permeation enhancers using flurbiprofen as a model drug

The efficacy and safety of commonly used enhancers were systemically evaluated by in vitro and in vivo methods in this study. Flurbiprofen was used as the model drug to examine the enhancing capacity of these enhancers. Both in vitro permeation by Franz cells and in vivo kinetics of skin disposition were performed to determine the flurbiprofen permeation by enhancers. Unsaturated fatty acids showed the greatest enhancement of flurbiprofen permeation. The enhancing effect of D-limonene was slightly lower than that of the fatty acids. Azone and L-alpha-lecithin even reduced the skin deposition by flurbiprofen application. In vitro prostaglandin E(2) (PGE(2)) release by cell culture, in vivo transepidermal water loss (TEWL) and colorimetry, and skin morphological changes were determined to examine the irritation of the skin by enhancers. The results showed that skin disruption and inflammation did not necessary correspond to the enhancing efficiency of the enhancers. Moreover, some discrepancies were observed in these irritant profiles when using various methods. The fatty acids generally showed the most irritating properties, followed by Azone, D-limonene, and L-alpha-lecithin. A complete portrait of the efficacy and safety of commonly used enhancers was therefore established in this study.     

Essential oils in niosomes for enhanced transdermal delivery of felodipine

The fluidity of vesicular membrane affects vesicular transdermal drug delivery. Essential oils can be located in vesicular membrane imparting flexibility and influencing transdermal delivery. Accordingly, the objective was to investigate the effect of incorporation of essential oils in niosomes on felodipine transdermal delivery. Rigid niosomes comprising Span 60 with cholesterol (2:1, w/w) were used with clove, eucalyptus or lemon oils being incorporated in the vesicles at increasing concentrations. The vesicle size and shape was monitored using scanning electron microscopy. Thermal analysis was used to monitor the thermal behavior. Drug entrapment efficiency, release and skin permeation were monitored. Niosomes were spherical with size ranging from 279 to 345?nm. The drug entrapment ranged from 97.9 to 98.8%. Thermal analysis confirmed the existence of oils within vesicular membrane and highlighted the membrane fluidizing effect. Drug release depended on the oil with clove oil or eucalyptus oil showing a trend of increased drug release compared with plain niosomes. In contrast, lemon oil reduced drug release rate. Skin permeation study reflected the superiority of oil containing niosomes. The results correlated with the fluidizing and penetration enhancing effects of oils. The study introduced essential oils as potential niosomes fluidizing agents for enhanced transdermal drug delivery.     

川芎挥发油对氟比洛芬渗透离体大鼠皮肤的促进作用

目的：研究川芎挥发油的体外促透作用及机制。方法：超临界萃取川芎挥发油，气相色谱-质谱法分析成分，以大鼠皮肤为渗透屏障，氟比洛济为模型药物，Franz扩散池法考察透皮特性，HPLC法测定大鼠皮肤中药物含量。结果：苯酞（91．15％）和萜烯（5．19％）组成的川芎挥发油具有显著的促透作用，但其强度低于同浓度的油酸;3％的挥发油具有最强的促透作用，随着挥发油浓度的增加，促透作用反而下降；透皮流量和皮肤滞留药量之间具有相关性。结论：川芎挥发油能显著增强氟比洛芬的透皮吸收，其作用机制可能是通过破坏角质层的结构，增加皮肤中的药物分配。其促透的物质基础可能是苯酞化合物。     

Preparation of hydrogels of griseofulvin for dermal application

In an attempt to prepare topical formulations of griseofulvin that can deliver the drug locally in effective concentration, various hydrogel formulations were prepared using carbomer (940 NF) as base; essential oils, propylene glycol (PG), N-methyl-2-pyrrolidone (NMP) as penetration enhancers. The in vitro skin permeation studies through Laca mouse skin were performed using vertical type cells. PG in the hydrogel formulation was found to influence drug release rate by increasing its solubility and partitioning. Further combinations of PG with varying amounts of NMP in the hydrogel formulations exhibited a significantly greater increase in the flux on comparison with the control and formulation containing PG alone. The diffusion samples obtained by in vitro permeation studies through mouse skin when subjected to microbioassay using Microsporum gypseum as tester microorganism exhibited antifungal activity. This indicates that the drug permeated through the mouse skin possess sufficient antifungal activity in vitro against the tested microorganism. The prepared hydrogels did not show any skin sensitization and histological studies were carried out to check the safety of permeation enhancers used. Further these formulations were found to be stable at three different temperatures 4, 25 and 40 degrees C with respect to percent drug content, release characteristics, pH, transparency, feel and viscosity.     

Transdermal delivery of tea catechins and theophylline enhanced by terpenes: a mechanistic study

Using in vitro and in vivo techniques, terpenes were evaluated as enhancers to improve the skin permeation of therapeutically active agents derived from tea, including tea catechins and theophylline. The in vitro permeation was determined by Franz cells. The skin deposition and subcutaneous amounts of drugs sampled by microdialysis were evaluated in vivo. Terpenes varied in their activities of enhancing drug permeation. The oxygen-containing terpenes were effective enhancers of drug permeation, whereas the hydrocarbon terpenes were much less efficient. Oxygen-containing terpenes with a bicyclic structure had reduced enhancing activity. Terpenes enhanced tea catechin permeation to a much greater degree than they did theophylline. The isomers of (+)-catechin and (-)-epicatechin showed different permeation behaviors when incorporated with terpenes. In the in vivo status, terpenes promoted the skin uptake but not the subsequent subcutaneous concentration of (-)-epigallocatechin gallate (EGCG). Both increased skin/vehicle partitioning and lipid bilayer disruption of the stratum corneum (SC) contributed the enhancing mechanisms of terpenes for topically applied tea catechins and theophylline based on the experimental results from the partition coefficient and transepidermal water loss (TEWL). alpha-Terpineol was found to be the best enhancer for catechins and theophylline. The high enhancement by alpha-terpineol was due to macroscopic perturbation of the SC and the biological reaction in viable skin as evaluated by TEWL and colorimetry.     

Water-activated, pH-controlled patch in transdermal administration of timolol. I. Preclinical tests.

Previously, transdermal patches with internal pH-controlled release were described. The aim of this study was to test the suitability of the patch design in transdermal delivery and, further, to select such transdermal patch formulations to a clinical study with timolol. In vitro release of timolol from the patches was determined as well as timolol permeation across the human cadaver skin. The effect of the skin on drug release were evaluated in vitro. In vitro data and pharmacokinetic parameters from the literature were used to construct a pharmacokinetic model for the prediction of in vivo performance of the devices. With water-activated, pH-controlled silicone reservoir devices, both the rate of drug release and the duration of constant release were controlled. The rate of timolol release was decreased when the devices were placed on human cadaver skin, and thus, the skin partly controls the rate and extent of timolol delivery to the systemic circulation in vivo. On the basis of in vitro data and kinetic simulations, devices of 10-cm(2) volume releasing timolol in vitro at the rates of 119 and 10 microgh(-1)cm(-2) were selected for human tests.     

Fatty acids in Botryococcus braunii accelerate topical delivery of flurbiprofen into and across skin

To improve the drug absorption into and across the skin, fatty acids extracted from Botryococcus braunii were evaluated using in vitro and in vivo techniques with Wistar rats as the animal model. Palmitic acid (C16:0), oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) were the major components in the B. braunii extract. Topical delivery of flurbiprofen was significantly enhanced after pretreatment with 3% B. braunii extract for 30min in an in vitro Franz cell and in vivo pharmacokinetic studies. Pure unsaturated fatty acids were more-effective enhancers than the B. braunii extract. However, a greater irritant potential was also observed with those fatty acids than with the B. braunii extract according to the skin tolerance study as determined by transepidermal water loss (TEWL). Both human keratinocytes and skin fibroblasts showed a 1.5-2-fold increase in prostaglandin E(2) (PGE(2)) release as compared to the control. The findings in this study indicate that the fatty acids in B. braunii may be useful enhancers for flurbiprofen delivery via the skin.     

Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm2/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.     

In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels

The purpose of this study was designed to investigate the in vitro and in vivo skin absorption of capsaicin and nonivamide from hydrogels. Various commercialized creams of capsaicin were also compared with hydrogels. Both skin stripping technique and Mexameter were applied to evaluate the level of capsaicin and nonivamide retained in stratum corneum (SC) and skin erythema in vivo. The partition of drug between skin and the hydrogel matrix was considered to play an important role in the permeation process. The in vitro permeation of capsaicin from hydrogels depends on the physicochemical nature and the concentration of the polymer used. The incorporation of nonionic Pluronic F-127 polymer into hydrogels resulted in a retarded release of capsaicin. On the other hand, the in vitro capsaicin permeation showed higher levels in cationic chitosan and anionic carboxymethyl cellulose (CMC) hydrogels than cream bases. The permeation of nonivamide was retarded at the late stage of in vitro application. The inter-subject variation was more significant in the in vivo study than in vitro skin permeation experiments. The cream induced in vivo skin erythema depending on the drug concentration, however, the dose-dependence was not observed in hydrogels. Nonivamide-treated skin showed stronger erythema than capsaicin-treated skin. The present study indicates that there is a moderate correlation between in vitro skin permeation and in vivo erythema responses of topically applied capsaicin and nonivamide. The correlation between drug amount in SC and skin erythema test in vivo was also observed.     

Transdermal atenolol releasing system: an approach towards its development

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC0-28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC0-28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.     

Stratum corneum permeation and percutaneous drug delivery of hydrophilic molecules enhanced by cryopneumatic and photopneumatic technologies

Novel cryopneumatic technology (CPx) and photopneumatic technology (PPx) have been developed to enhance the permeation of the stratum corneum (SC) and percutaneous drug delivery (PDD). CPx produces micro-cracks at the skin surface by successively freezing and stretching the skin with vacuum suction. PPx combines stretching of the skin by vacuum suction with intense pulsed light. The enhancing effects of CPx and PPx were studied on ex vivo porcine skin and in vivo human skin models. Fluorescent hydrophilic macromolecules (FITC and FITC-Dextran) were used as drug surrogates. Fluorescent images of in vivo experiments show that the enhancing effect of CPx is due to drug permeation through the micro-cracks produced by freezing stretching cycles, while PPx could promote drug permeation through sweat glands. Both ex vivo and in vivo results strongly suggest that CPx and PPx can effectively enhance the permeation of the SC and PDD for the delivery of hydrophilic macromolecules.     

In vivo and in vitro evaluation of essential oils from Ligusticum chuanxiong Hort on the transdermal delivery of flurbiprofen in rabbits

The present study was designed to evaluate skin permeation enhancement effect of essential oils from Ligusticum chuanxiong HORT (chuanxiong oil) in rabbits and to compare the in vivo absorption and in vitro permeation using flurbiprofen as a model drug. In vivo results demonstrated that chuanxiong oil showed a rapid and marked permeation enhancement effect. The group with 10% oil exhibited the highest value of area under the curve (AUC) of 418+/-124 mug/ml.h, which was 2.43 times the high of control. The AUC value of 3% oil group (245+/-81.6 mug/ml.h) was similar to that of 5% oleic acid group (235+/-74.5 mug/ml.h). Whereas in vitro results indicated the enhancement of chuanxiong oil was relatively weak. The group with 3% oil appeared to the highest flurbiprofen flux (84.9+/-19.3 mug/cm(2)/h), to some extent lower than 5% oleic acid group (107+/-5.85 mug/cm(2)/h). At 10% and 15% concentrations, chuanxiong oil even decreased the flux of flurbiprofen compared with the control. Both in vitro results with pretreated skin and flurbiprofen content accumulated in skin indicated the potential mechanism for the in vitro enhancement of chuanxiong oil was the weakened barrier function by improving in the partitioning of flurbiprofen to the stratum corneum. The discrepancy was noted between the in vivo and in vitro results, indicating only about the weakened barrier function was not enough to explain the sharply increment of in vivo absorption of flurbiprofen by chuanxiong oil. The GS-MS results indicated phthalides identified from chuanxiong oil might mainly contribute to enhance in vivo absorption of flurbiprofen because of its large quantities (91.15%).     

Drug release kinetics from polymeric films containing propranolol hydrochloride for transdermal use

Polymeric films containing propranolol hydrochloride (PPN) were formulated and evaluated with a view to select a suitable formulation for the development of transdermal drug delivery systems. Films containing different ratios of ethyl cellulose (EC), poly(vinylpyrrolidone) (PVP), and PPN were prepared by mercury substrate method. In vitro drug release and skin permeation studies were conducted using paddle over disk and modified Franz diffusion cell, respectively. The drug release profiles from the polymeric film indicated that the drug content in the film decreased at an apparent first-order rate, whereas the quantity of drug release was proportional to the square root of time. The release rate of PPN increased linearly with increasing drug concentration and PVP fraction in the film, but was found to be independent of film thickness. The increase in release rate may be due to leaching of hydrophilic fraction of the film former, which resulted in the formation of pores. It was also observed that the release of drug from the films followed the diffusion-controlled model at low drug concentration. A burst effect was observed initially, however, at high drug loading level, which may be due to rapid dissolution of the surface drug followed by the diffusion of the drug through the polymer network in the film. The in vitro skin permeation profiles displayed increased flux values with increase of initial drug concentration in the film, and also with the PVP content. From this study, it is concluded that the films composed of EC/PVP/PPN, 9:1:3, 8:2:2, and 8:2:3, should be selected for the development of transdermal drug delivery systems using a suitable adhesive layer and backing membrane for potential therapeutic applications.     

Development and in-vitro evaluation of transdermal matrix films of metoprolol tartrate

The transdermal matrix films of metoprolol tartrate (MT) were prepared by casting on mercury substrate employing different ratios of polymers, ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP), using dibutyl phthalate (DBT) as a plasticizer. Four formulations were prepared. Formulations MF-1, MF-2, MF-3 and MF-4 were composed of EC and PVP in the following ratios: 4.5:0.5, 4:1, 3:2 and 2:3 respectively. The formulations were subjected to various physical characterization studies namely, thickness, weight variation, drug content, moisture uptake, in vitro drug release and in vitro skin permeation. The in vitro permeation studies were carried out across excised porcine ear skin using Franz diffusion cell. Cumulative amounts of the drug released in 24 hours from the four formulations were 69.58%, 96.13%, 98.85% and 99.60%, respectively. Corresponding values for the cumulated amounts of drug permeated across the porcine skin for the above matrix films were 124.38, 153.22, 156.46 and 163.25 mug/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model (r(2)=0.9147-0.9823), and the mechanism of release was diffusion mediated. Based on the physical evaluation, in vitro drug release & permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films MF-3, composed of EC: PVP (3:2), may be suitable for the development of a transdermal drug delivery system of MT.     

Study of tolnaftate release from fatty acids containing ointment and penetration into human skin ex vivo

Five fatty acids (oleic, linoleic, myristic, lauric and capric) were incorporated in 10% (w/w) into ointment formulation and their influence on lipophilic model drug tolnaftate release in vitro and enhancing effect on tolnaftate penetration into epidermis and dermis of human skin ex vivo were investigated. The prepared ointments were tested for homogeneity, pH and theological properties. In vitro release studies and ex vivo skin penetration experiments were carried out using Hanson and Bronaugh-type flow-through diffusion cells, respectively. Tolnaftate cumulative amount liberated from semisolids was assayed using UV-Vis spectrophotometer. After in vitro skin penetration studies, appropriately extracted human skin layers were analyzed for tolnaftate content using a validated HPLC method. Statistical analysis revealed that release rate of tolnaftate from control ointment and ointments with fatty acids was not significantly different and only 7.34-8.98% of drug was liberated into an acceptor medium after 6 h. Tolnaftate amount penetrating into 1 cm2 of epidermis from ointments containing oleic, linoleic, myristic and lauric acids was significantly greater (p < 0.05) than from the control ointment. Penetration enhancing ratios for these fatty acids for tolnaftate penetration into epidermis ranged from 1.48 to 1.75. In conclusion, fatty acids did not increase the liberation of tolnaftate from ointment formulation, but demonstrated their enhancing effect on tolnaftate penetration into human epidermis in vitro. Results from in vitro release experiments do not suit for prediction of the situation in the skin in vitro, if chemical penetration enhancers are incorporated into the ointment formulation.     

Differential regulation of bradykinin receptor density, intracellular Ca2+, and prostanoid release in skin and foreskin fibroblasts. Effects of cell density and interleukin-1alpha.

1. Bradykinin (BK) receptors, cytosolic Ca2+, and prostanoids were studied in human skin and foreskin fibroblasts. 2. Bmax values of BK receptors were higher in foreskin than in skin fibroblasts, increasing with cell densities in both cell types. IL-1alpha-dependent receptor induction was blocked by cycloheximide. 3. BK-stimulated cytosolic Ca2+ elevation was higher in confluent than in non-confluent cultures and larger in foreskin than in skin fibroblasts. Responses were not enhanced after IL-1-alpha-induced up-regulation of BK receptors. 4. Intrinsic prostanoid production was higher in foreskin than in skin fibroblasts at comparable cell densities. In foreskin, but not in skin fibroblasts, BK stimulation increased the release of PGE2 10 fold and that of 6-oxo-PGF1alpha 6-7 fold. 5. Preincubation with IL-1alpha had a marked effect on prostanoid release in foreskin fibroblasts only. Subsequent BK stimulation increased the release of PGE2 and 6-oxo-PGF1alpha 7-10 fold in skin fibroblasts while this increase was only 30% in foreskin fibroblasts. Release of TXA2 reached values up to one third of the other prostanoids. The IL-1alpha induced rise in BK-stimulated PGE2 synthesis was fully abolished by specific inhibition of cyclo-oxygenase 2. 6. IL-1alpha sensitized BK-stimulated prostanoid synthesis and modulated prostanoid patterns differently in fibroblasts from skin and foreskin. The IL-1alpha effects on prostanoid release were not related to BK receptor numbers nor to the BK-stimulated Ca2+ signal but appear to be due to induction of prostanoid synthesizing enzymes. Foreskin fibroblasts seem to be unique and significantly different from fibroblasts of other skin locations in respect to their response to inflammation-associated kinins and cytokines.     

Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages.

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.     

固体脂质纳米粒作为水杨酸经皮给药载体的研究

目的 考察固体脂质纳米粒作为经皮给药载体对水杨酸经皮吸收的促渗透作用.方法 采用薄膜超声法制备水杨酸固体脂质纳米粒,以改良的Franz扩散池考察其体外透皮特性;并与水杨酸软膏剂比较,考察其促渗作用.结果 制备的水杨酸固体脂质纳米粒均匀圆整,包封率为46.4%,体外透皮特性优于普通软膏剂,24 h后皮肤药物累积透过量为654.3 μg/cm2,皮肤中药物残留量为22.99 μg,均分别显署高于软膏剂组(128.0 μg/cm2和0.84 μg,P<0.05).结论 固体脂质纳米粒作为水杨酸经皮给药载体,可有效促进药物透皮吸收和增加药物在皮肤中储留量,而且可延缓药物的释放,从而有效提高药物疗效及患者依从性.     

Development of matrix-membrane transdermal drug delivery system for atenolol

A polymer matrix system for transdermal delivery of Atenolol was developed for its prolonged and controlled release systemic availability. To achieve the desired and controlled release rate, different combinations of Eudragit RL with polyvinyl pyrrolidone and polyethylene glycol 4000 were used in the preparations of polymeric matrix system. These preparations were evaluated for in vitro release and permeation of the drug across pig skin. The desired systems exhibited linear relationship between drug release (Q) versus ne^0.8(hr^0.8). The product exhibiting required skin permeation 64 mcg/h/cm² to achieve an effective plasma concentration was selected for the in vivo performance evaluation. The drug plasma profile was compared with the plasma profile obtained following the administration of a conventional oral dose of Atenolol. The study revealed that the designed polymeric matrix transdermal drug delivery system of Atenolol could be successful with improved performance.