Cutaneous effects of transdermal levonorgestrel

The irritation of transdermal devices delivering levonorgestrel and the permeation enhancer ethyl acetate with or without ethanol was evaluated in rabbits. Erythema and oedema were assessed 24, 48 and 72 hr and 7 days after application of the 24-hr delivery system. The devices were found to be mild to moderately irritating, with erythema the primary manifestation. No differences were observed between devices using pure ethyl acetate or ethyl acetate-ethanol (7:3, v/v) as enhancers. Devices using pure ethanol as an enhancer gave levels of irritation similar to those using ethyl acetate-ethanol (7:3) or pure ethyl acetate. Control devices containing only water (no drug) were also found to be mildly irritating to rabbits following a 24-hr exposure period. A histological evaluation of the application sites of two of the formulations confirmed the visual observations of mild subacute irritation. The changes produced by transdermal levonorgestrel were reversible. The problems of skin irritation of transdermal devices is discussed with particular reference to the use of ethyl acetate and ethanol as skin penetration enhancers.     

Transdermal delivery of levonorgestrel. IV: Evaluation of membranes

A series of experiments were performed to evaluate the flux of levonorgestrel (LN), ethyl acetate (EtAc), and ethanol (EtOH) through excised rat skin, through a variety of synthetic membranes and through membranes supported on rat skin. Using a donor phase of EtAc:EtOH (7:3) containing excess solid LN, the flux of LN through rat skin was approximately 1.0 microgramc/cm2.h. The normalized fluxes of LN, EtAc, and EtOH through ethylene vinyl acetate (EVAc) copolymers of varying vinyl acetate (VAc) content (12 to 25%) were 1.3 to 3.1 x 10(-8), 2.6 to 6.8 x 10(-4), and 4.8 to 9.9 x 10(-5) g.cm/cm2.h, respectively. Permeability experiments were also performed with the EVAc membranes supported on rat skin. By selecting the VAc content and thickness of the EVAc membranes, it was possible to control the delivery of enhancer (EtAc:EtOH) through rat skin (membrane-rate control) or to let the skin control the overall delivery of enhancer.     

Pharmacological evaluation of membrane-moderated transdermal system of glipizide

1. Membrane-moderated transdermal systems of glipizide were prepared using drug-containing carbopol gel (drug reservoir) and ethyl cellulose, as well as Eudragit RS-100, Eudragit RL-100 (Rohm Pharma, Darmstadt, Germany) and ethylene vinyl acetate (EVA; 2, 9 and 19% vinyl acetate content) rate-controlling membranes, and were subsequently evaluated in vitro (drug content and drug permeation studies) and in vivo (acute and long-term hypoglycaemic activity, effect on glucose tolerance, biochemical and histopathological studies, skin irritation test and pharmacokinetic studies in mice). 2. The drug content of the systems was found to be more than 99%. Variations in drug permeation patterns were observed among the formulations containing different rate-controlling membranes. 3. The system with the EVA (19% vinyl acetate) rate-controlling membrane was selected for in vivo experiments. This transdermal system produced better improvement with respect to hypoglycaemic activity, glucose tolerance and tested biochemical, histopathological and pharmacokinetic parameters all compared with oral administration and exhibited negligible skin irritation. 4. The transdermal system successfully prevented severe hypoglycaemia in the initial hours and it was also effective for chronic application.     

Controlled systemic delivery of indomethacin using membrane-moderated, cream formulation-based transdermal devices

The present study was carried out to design a viable and practically effective transdermal systems of indomethacin using cream-based drug reservoirs and suitable rate controlling membranes. As vehicles, a more lipophilic base (F(1)) and a cream formulation containing predominant aqueous phase (F(2)) were chosen to study the influence of vehicle nature and role of permeation enhancers that increases thermodynamic activity and to provide diffusible species of drug to skin. Rate controlling membranes of cellulose acetate (CA) and ethyl cellulose (EC) with polyvinyl pyrollidine and hydroxypropyl methyl cellulose were used to design transdermal devices. In vivo, effective plasma concentrations of indomethacin are maintained up to 24 hr whereas oral formulation showed only up to 8 hr. Although the plasma drug levels between both EC films differ insignificantly, PVP film showed a better pharmacokinetic profile. The pharmacodynamic performance of the transdermal devices exhibited good anti-inflammatory activity over 24 hr compared with orally administered indomethacin. In vivo studies indicate the superiority of CA films over the EC films. Further, enhancement may be achieved with other classic enhancers/enhancement strategies with such devices containing aqueous cream vehicle and the optimum membranes.     

Controlled Systemic Delivery of Indomethacin Using Membrane-Moderated,Cream Formulation–Based Transdermal Devices

The present study was carried out to design a viable and practically effective transdermal systems of indomethacin using cream-based drug reservoirs and suitable rate controlling membranes. As vehicles, a more lipophilic base (F₁) and a cream formulation containing predominant aqueous phase (F₂) were chosen to study the influence of vehicle nature and role of permeation enhancers that increases thermodynamic activity and to provide diffusible species of drug to skin. Rate controlling membranes of cellulose acetate (CA) and ethyl cellulose (EC) with polyvinyl pyrollidine and hydroxypropyl methyl cellulose were used to design transdermal devices. In vivo, effective plasma concentrations of indomethacin are maintained up to 24 hr whereas oral formulation showed only up to 8 hr. Although the plasma drug levels between both EC films differ insignificantly, PVP film showed a better pharmacokinetic profile. The pharmacodynamic performance of the transdermal devices exhibited good anti-inflammatory activity over 24 hr compared with orally administered indomethacin. In vivo studies indicate the superiority of CA films over the EC films. Further, enhancement may be achieved with other classic enhancers/enhancement strategies with such devices containing aqueous cream vehicle and the optimum membranes.     

Enhanced transdermal absorption and pharmacokinetic evaluation of pranoprofen-ethylene-vinyl acetate matrix containing penetration enhancer in rats

To increase the skin permeation of pranoprofen from the ethylene-vinyl acetate (EVA) matrix, different types of enhancers were added to an EVA matrix containing 2% pranoprofen. The pharmacokinetics and bioavailability of pranoprofen, an anti-inflammatory drug, were examined to determine the feasibility of an enhanced transdermal delivery system for pranoprofen from an EVA matrix containing caprylic acid as the enhancer in rats. The effects of the enhancers on the level of pranoprofen permeation through the skin were evaluated using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, including the fatty acids (saturated, unsaturated), the glycols, the glycerides, and the pyrrolidones, caprylic acid showed the best enhancement. A pranoprofen-EVA matrix system was formulated containing caprylic acid as an enhancer. The pranoprofen-EVA matrix system (8 mg/kg) was applied to the abdominal skin of rats. The blood samples were collected through the femoral artery for 24 h and the plasma concentrations of pranoprofen were determined by HPLC. The pharmacokinetic parameters were calculated using the MULTI computer program. The area under the curve (AUC) was significantly higher in the enhancer group (55.49 ± 13.87 ng/mL·h) than in the control group (22.48 ± 5.63 ng/mL·h), which was treated transdermally without the enhancer, showing about 246% increased bioavailability (p<0.05). As the pranoprofen-EVA matrix containing caprylic acid as an enhancer was administered to rats via the transdermal routes, the relative bioavailability increased about 2.46-fold compared to the control group, showing a relatively constant, sustained blood concentration. These results show that a pranoprofen-EVA matrix containing a permeation enhancer could be developed as a transdermal delivery system to provide a sustained plasma concentration.     

Transdermal delivery of flurbiprofen: permeation enhancement, design, pharmacokinetic, and pharmacodynamic studies in albino rats

The enhancing effects of lemon oil on the transdermal penetration of flurbiprofen through rat skin invitro and in vivo was investigated. The maximum flux achieved by Isopropyl alcohol (IPA):Propylene glycol (PG) (70:30% v/v) solvent mixture was further increased by lemon oil. The flux of flurbiprofen through ethylene vinyl acetate microporous membrane was evaluated. The membrane altered the flux of flurbiprofen significantly. The reservoir type of transdermal patch was fabricated using flurbiprofen viscous system, ethylene vinyl acetate membrane, and backing film. Histological investigations were done on rat skin samples treated with solvent systems with or without penetration enhancer for 24 hr. No skin irritation was seen. Lemon oil produced more pronounced change in stratum corneum and the epidermis as compared with the control groups. The pharmacokinetics of flurbiprofen in albino rats following application of a transdermal patch for 24 hr was evaluated. The maximum plasma concentration (C(max)) and AUC(0-alpha) of the patch formulation was 1.7 and 1.6 times, increased respectively as compared with the control patch formulation. Quantity of the drug accumulated in the excised skin to which test patch formulation was applied was more than the one to which control patch formulation was applied. Anti-inflammatory effect in the Carrageenin-induced paw edema in rat was significantly higher than the control patch formulation.     

Formulation and evaluation of limonene-based membrane-moderated transdermal therapeutic system of nimodipine

The aim of the present study was to design a membranemoderated transdermal therapeutic system (TTS) of nimodipine using 2% w/w hydroxypropyl methylcellulose (HPMC) gel as a reservoir system containing 4% w/w of limonene as a penetration enhancer. The permeability flux of nimodipine through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer (9 to 28%). The effect of pressure-sensitive adhesives such as TACKWHITE A 4MED® on the permeability of nimodipine through EVA membrane 2825 (28% w/w vinyl acetate) or membrane/rat skin composite also was studied. The permeability flux of nimodipine from the chosen EVA 2825 (with 28% vinyl acetate content) was 159.72 ± 1.96 μg/cm²/hr, and this flux further decreased to 141.85 ± 1.54 μg/cm²/hr on application of pressure-sensitive adhesive (TACKWHITE A 4MED®). However, the transdermal permeability flux of nimodipine across EVA 2825 membrane coated with TACKWHITE A 4MED®/rat skin composite was found to be 126.59 ± 2.72 μg/cm²/hr, which is 1.3-fold greater than the required flux. Thus, a new transdermal therapeutic system for nimodipine was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED® and 2% w/w HPMC gel as reservoir containing 4% w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nimodipine, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 20 hr with improved bioavailability in comparison with the immediate release tablet dosage form.     

Enhanced transdermal delivery of triprolidine from the ethylene-vinyl acetate matrix.

Triprolidine-containing matrix was fabricated with ethylene-vinyl acetate (EVA) copolymer to control the release of the drug. The permeation rate of triprolidine in the stripped skin was greatly larger than that in the whole skin. Thus it showed that the stratum corneum acts as a barrier of skin permeation. The effect of penetration enhancer and stripping of skin on the permeation of triprolidine through the excised mouse skin was studied. Penetrating enhancers showed increased flux probably due to the enhancing effect on the skin barrier, the stratum corneum. Among enhancers used such as glycols, fatty acids and non-ionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The permeability of triprolidine was markedly increased with stripping of the mouse skin to remove the stratum corneum that acts as a barrier of skin permeation. For the controlling transdermal delivery of triprolidine, the application of EVA membrane containing permeation enhancer could be useful in the development of transdermal drug delivery system.     

A combined approach of chemical enhancers and sonophoresis for the transdermal delivery of tizanidine hydrochloride

The effects of chemical enhancers and sonophoresis on the transdermal permeation of tizanidine hydrochloride (TIZ) across mouse skin were investigated. Parameters including drug solubility, apparent partition coefficient (APC), drug permeation, and degradation in skin were determined. Low frequency ultrasound was also applied in the presence and absence of chemical enhancers to assess whether drug permeation improved. APC values indicated that TIZ preferentially partitions into intercellular spaces and does not form a reservoir, with the drug also exhibiting good enzymatic stability in skin. Most of the enhancers studied significantly increased the permeation rate of TIZ through full thickness mouse skin in comparison with TIZ formulated in phosphate buffer. Maximum enhancement was observed for TIZ formulated as a suspension in 50% v/v aqueous ethanol containing 5% v/v citral. Sonophoresis significantly (p < 0.05) increased the cumulative amount of TIZ permeating through the skin at 15 and 30 min in comparison to passive diffusion. A synergistic effect was noted when sonophoresis was applied in the presence of chemical enhancers. The results suggest that the formulation of TIZ with an appropriate penetration enhancer may be useful in the development of a therapeutic system to deliver TIZ across the skin for a prolonged period, i.e. 24 hr. The application of ultrasound in association with chemical enhancers, such as the combination of 5% v/v citral in 50% v/v aqueous ethanol, could further serve as a non-oral and non-invasive drug delivery modality for the immediate therapeutic effect of muscle relaxants such as TIZ.     

Enhanced transdermal controlled delivery of glimepiride from the ethylene-vinyl acetate matrix

An ethylene-vinyl acetate (EVA) matrix containing glimepiride was prepared as a potential transdermal drug delivery system. Permeation studies of quinupramine through the EVA copolymer membrane were carried out using a two-chamber diffusion cell. The rate of drug permeation through the EVA membrane was proportional to the PEG 400 volume fraction. The release of glimepiride from the EVA matrix was examined using a modified Franz diffusion cell. A plasticizer was added to prepare the pore structure of the EVA matrix in order to increase the rate of drug release. The effects of PEG 400, drug concentration, temperature, and plasticizer on the drug release rate were investigated. Various types of enhancers were added to an EVA matrix containing 2% glimepiride in an attempt to increase the level of skin permeation of quinupramine through an EVA matrix. The effects of the enhancers on the level of glimepiride permeation through the skin were evaluated using Franz diffusion cells fitted with intact excised rat skin. The rate of drug release from the EVA matrix increased with increasing PEG 400 volume fraction, temperature, and drug loading. The estimated activation energy of drug release was 7.274 kcal/mol for 2% drug loading dose. The release of glimepiride from the EVA matrix followed a diffusion-controlled model, where the quantity released per unit area was proportional to the square root of time. The controlled release of glimepiride was achieved using the EVA polymer including the plasticizer. Among the plasticizers used, such as the alkyl citrates and phthalates groups, diethyl phthalate slightly increased the rate of glimepiride release. Among the various enhancers used, such as the non-ionic surfactants, the glycerides, the propylene glycol derivatives, fatty acids (saturated or unsaturated), and pyrrolidones, linoleic acid showed the highest permeation rate; 3.17-times higher than the control. In conclusion, an EVA matrix containing a permeation enhancer can be used for the transdermal controlled delivery of glimepiride.     

Development of a membrane-controlled transdermal therapeutic system containing isosorbide dinitrate

The formulation of a transdermal delivery system for isosorbide dinitrate (ISDN) was examined. It was found that the target release rate should be 4.01 mg/h per 20 cm² for optimal dosing. In order to reach such this zero order release rate, a membrane permeation controlled transdermal therapeutic system (TTS) formulation was developed, with ethylene vinyl acetate copolymer (EVAC) and polyethylene (PE) membranes as rate controlling membranes; a carbomer gel was used as the drug reservoir. The release of ISDN from this drug delivery device was studied in vitro using FDA recommended method. PIB adhesive on the EVAC or PE membrane caused a decreased flux of ISDN; the release kinetics fitted Higuchi matrix kinetics. TTS with EVAC membrane release ISDN at a rate much lower than the calculated target release rate, but with PE membranes, the release rate was very close to the target. Release rate studies have revealed that, as the VA content in EVAC membrane increased, the flux of ISDN increased. All these results were compared with the commercial product Frandol^® Tape S from Japan. It was found that the release rate of Frandol was close to target release rate and fitted matrix kinetics. These results suggested that TTS that contain PE membrane as rate controlling membrane, polyisobutylene (PIB) adhesive and carbomer gel as a reservoir can be applicable as a TTS for ISDN.     

Development and Biopharmaceutical Evaluation of Quinupramine-EVA Matrix Containing Penetration Enhancer for the Enhanced Transdermal Absorption in Rats

To increase the skin permeation of quinupramine through the rat skin, different types of enhancers were added to an ethylene-vinyl acetate (EVA) matrix containing 2% quinupramine. The effects of the enhancers on the level of quinupramine permeation through the skin were evaluated by using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, which included fatty acids (saturated and unsaturated), glycerides, pyrrolidones, and nonionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The pharmacokinetics and bioavailability of quinupramine from an EVA matrix were examined to determine the level of percutaneous absorption in rats. The percutaneous absorption of quinupramine from the EVA matrix with or without an enhancer was investigated. Quinupramine was administered orally or intravenously to compare the pharmacokinetic parameters with that of the transdermal route. The relative bioavailability of quinupramine in the matrix containing polyoxyethylene-2-oleyl ether as an enhancer was approximately 2.81 times higher than the group without an enhancer. Histological examination revealed that the skin pretreated with the EVA matrix containing the enhancers had a loosely layered stratum corneum. These results show that the quinupramine-EVA matrix containing a permeation enhancer could be a good transdermal delivery system for providing sustained plasma concentrations.     

Transdermal delivery of fentanyl from matrix and reservoir systems: Effect of heat and compromised skin

The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the current research focuses on the in vitro characterization of fentanyl reservoir (Duragesic®) and matrix (Mylan) systems with respect to drug release and skin permeation under conditions of elevated temperature and compromised skin. In addition, different synthetic membrane barriers were evaluated to identify the one that best simulates fentanyl skin transport, and thus may be useful as a model for these systems in future studies. The results indicate that reservoir and matrix FTS are comparable when applied to intact skin at normal skin temperature but the kinetics of drug delivery are different in the two systems. At 40°C, the permeation rate of fentanyl was twice that seen at 32°C over the first 24 h in both systems; however, the total drug permeation in 72 h is significantly higher in the reservoir FTS. When applied to partially compromised skin, matrix FTS has a greater permeation enhancement effect than reservoir FTS. The intrinsic rate limiting membrane of the reservoir system served to limit drug permeation when the skin (barrier) permeability was compromised. Different ethylene vinyl acetate membranes were shown to have fentanyl permeability values encompassing the variability in human skin. Results using the in vitro model developed using synthetic membranes suggest that they mimic the effect of compromised skin on fentanyl permeability. Especially for highly potent drugs such as fentanyl, it is important that patients follow instructions regarding application of heat and use of the product on compromised skin. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2357–2366, 2010     

In vitro and In vivo characterization of the transdermal delivery of sertraline hydrochloride Films

Background and the purpose of the study

Sertraline hydrochloride is a selective serotonin reuptake inhibitor principally used in the treatment of major depressive disorder. To maintain the therapeutic plasma drug concentration of the drug for prolonged period, the transdermal drug delivery has been chosen as an alternative route of drug delivery. The pharmacokinetic properties of sertraline hydrochloride make it suitable for transdermal delivery. The purpose of the study was to investigate the effect of polymers and penetration enhancers on the transdermal delivery of the drug in order to improve its therapeutic efficacy.

Methods

In the preparation of films, Eudragit RL 100, Eudragit RS 100, hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose were used as polymers. The films were characterized for thickness, tensile strength, drug content, moisture uptake, moisture content, water vapor transmission rate and drug release. The films exhibiting higher rates of drug release were subjected to study the effect of oleic acid and propylene glycol as penetration enhancers on skin permeation of sertraline hydrochloride. In vivo and skin irritation studies were performed for the optimized film.

Results

Films containing Eudragit RL 100, Eudragit RL 100 and HPMC showed the highest drug release of 94.34% and 96.90% respectively in a period of 42 hrs. The release data fitted into kinetic equations, yielded zero-order and fickian mechanism of drug release. There was a two-fold increase in skin permeation of sertraline hydrochloride in the presence of penetration enhancers in the film. The physical evaluation indicated the formation of smooth, flexible and translucent films. No skin irritation occurred on rabbit skin and the infrared studies showed the compatibility of the drug with the formulation excipients. The in vivo study revealed a constant plasma concentration of drug for long periods and the films containing penetration enhancers had achieved adequate plasma levels of the drug.

Conclusions

The obtained results indicated the feasibility for transdermal delivery of sertraline hydrochloride using eudragit RL 100 and HPMC.     

Enhanced transdermal delivery of atenolol from the ethylene-vinyl acetate matrix

To enhance transdermal delivery of atenolol, ethylene-vinyl acetate (EVA) matrix of drug containing penetration enhancer was fabricated. Effect of penetration enhancer on the permeation of atenolol through the excised rat skin was studied. Penetrating enhancers showed the increased flux probably due to the enhancing effect on the skin barrier, the stratum corneum. Among enhancers used such as glycols, fatty acids and non-ionic surfactants, polyoxyethylene 2-oleyl ether showed the best enhancement. For the controlling transdermal delivery of atenolol, the application of EVA matrix containing permeation enhancer could be useful in the development of transdermal drug delivery system.     

Transdermal delivery of venlafaxine hydrochloride: the effects of enhancers on permeation across pig ear skin

Venlafaxine representing a new class of antidepressants is a potent serotonin/ norepinephrine reuptake inhibitor. Transdermal delivery of venlafaxine hydrochloride (VHCl) may result in proper patient compliance by reducing the incidence of the undesirable GI problems generally associated with its plural oral dosing. The present study is an attempt to investigate the improvement of the transdermal flux of the hydrophilic VHCl by certain permeation enhancers viz. glycerin, urea, propylene glycol and mixture of propylene glycol and ethanol across pig ear skin. The cumulative drug release was the highest from the formulation F5 consisting of the mixture of propylene glycol and ethanol in sodium alginate gel with a load of 25% w/w VHCl with 96% permeation enhancement. The steady state flux observed with F5 was 0.203 mg cm(-2) hr and an area of 15.27 cm(2) would suffice to arrive at a required therapeutic concentration of VHCl in the blood.     

Enhanced transdermal delivery of loratadine from the EVA matrix

Various enhancers, such as fatty acids (saturated, unsaturated), glycerides, propylene glycols, and non-ionic surfactants, have been incorporated in the loratadine-EVA matrix to increase the rate of skin permeation of loratadine from an EVA matrix. The enhancing effects of these enhancers on the skin permeation of loratadine were evaluated using a modified Keshary-Chien cell fitted with intact excised rat skin. The penetration enhancers showed a higher flux, probably due to the enhancing effect on the skin barrier, the stratum corneum. Among the enhancers used, such as the fatty acids, glycols, propylene glycols, and non-ionic surfactants, linoleic acid showed the best enhancement. For the enhanced transdermal delivery of loratadine, application of an EVA matrix containing a permeation enhancer might be useful in the development of a transdermal drug delivery system.     

Transdermal delivery of indomethacin and levonorgestrel using clofibric acid amides as penetration enhancers

The enhancing properties of clofibric acid amides on the transdermal delivery of indomethacin and levonorgestrel were studied in vitro using full-thickness hairless mouse skin. The enhancers possessed alkyl side chains varying from 2 (1) to 16 (7) carbons. Indomethacin was applied in propylene glycol and levonorgestrel in 1-butanol, and all enhancers were applied at 0.4 M in propylene glycol 1 h prior to drug treatment. 1-Butanol was chosen as the vehicle for levonorgestrel since it was found to deliver more drug transdermally than propylene glycol. Since this was a volatile solvent, all experiments with levonorgestrel were performed under occlusion. The greatest increases in permeability coefficients and skin retention of model drugs were observed with compounds 4, 5, and 6. The permeability coefficient enhancement ratio (ER) for indomethacin and 4 was 3.1, for 5 was 10.9, and for 6 was 14.6. Skin content ER values were 4.6, 5.3, and 1.8, respectively. Levonorgestrel permeability coefficient ER values were lower, 1.6 for 4, 2.6 for 5, and 1.9 for 6. Skin content ER values for this model drug were 1.7, 4.3, and 2.3, respectively. Azone, however, was less effective than 5 and 6 for both model drugs with respect to permeability coefficients and 24-h receptor concentrations. For skin contents and indomethacin, 2-7 were more effective than Azone, and for levonorgestrel, 5, 6, and 7. Indomethacin enhancement was dependent on concentration of enhancer 6 (0.1, 0.2, 0.4, 0.6, 0.8 M), the maximum being observed for 0.4, 0.6, and 0.8 M. Permeation enhancement of both drugs was dependent on the length of the alkyl side chain of the enhancer. It is proposed that these compounds may be useful for transdermal drug delivery, although further testing needs to be performed.     

Enhanced transdermal delivery of acyclovir sodium via elastic liposomes

The elastic liposomes bearing acyclovir sodium were prepared for its enhanced transdermal delivery by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, polydispersity index, turbidity and in vitro release pattern. Permeability studies of acyclovir sodium incorporated in elastic liposomes were performed across artificial membranes and rat skin. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy, that revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 microm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing acyclovir sodium was observed and the investigations revealed an enhanced transdermal flux (6.21 +/- 1.8 microg/cm(2)/hr) and decreased lag time (0.6 hr) for acyclovir sodium. The obtained flux was nearly 2.0 and 6.3 times higher than conventional liposomal formulation bearing acyclovir sodium and plain drug solution, respectively (p < 0.01). The elastic liposomal formulation for transdermal delivery of acyclovir sodium provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared with conventional liposomes. In vivo studies showed that on transdermal application of elastic liposomes, the concentration of acyclovir sodium in plasma was found to be 105 +/- 9.4 ng/ml after 24 hr which is about 4.2 times compared with conventional liposomes. Thus it is concluded that the elastic liposomes may be promising vehicles for the transdermal delivery of acyclovir sodium.