The influence of vehicles on skin penetration

Barrett, C. W.; Hadgraft, Jonathan; Sárkány, I.

doi:10.1111/j.2042-7158.1964.tb07545.x

Cited by 36 publications

(16 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The effect of PEG on skin penetration has been postulated to be due to a drug-vehicle interaction that results in a lower thermodynamic activity of the drug (4,8,9). Other researchers have suggested that the retardant effect of PEG is due to its inability to hydrate the stratum corneum or to a relative osmotic effect which tends to dehydrate the stratum corneum (2).…”

Section: Resultsmentioning

confidence: 99%

Failure of topical acyclovir in ointment to penetrate human skin

Freeman¹,

Sheth²,

Spruance³

1986

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Topical acyclovir (ACV) in polyethylene glycol (PEG) ointment has been disappointing in the treatment of recurrent herpes simplex virus infections in immunocompetent patients. To investigate the possible role of poor drug delivery from this formulation, we studied the penetration of ACV through excised human skin from three vehicles; PEG ointment, modified aqueous cream, and dimethyl sulfoxide. A second antiviral agent, idoxuridine, was studied in the same formulations, and drug delivery through excised guinea pig skin was also assessed for comparison. The delivery of ACV from PEG ointment was very slow for both human and guinea pig skin (drug flux, 0.055 and 0.047 tLg/cm2 per h, respectively). Formulation of ACV in modified aqueous cream and in dimethyl sulfoxide resulted in an 8-and 60-fold increase, respectively, in the flux of ACV through human skin. Idoxuridine behaved similarly to ACV in the three vehicles. The poor clinical results seen with topical use of ACV ointment may be due in part to retarded drug delivery from this formulation.Topically administered acyclovir (ACV) in polyethylene glycol (PEG; Zovirax Ointment; Burroughs Wellcome Co., Research Triangle Park, N.C.) has proved disappointing in the therapy of recurrent herpes simplex virus (HSV) infections in immunocompetent patients, including trials in which therapy was patient initiated (3,10,12,15,17). Investigators have speculated from this experience that the failure of topical ACV therapy is due in part to the inability of ACV to penetrate the stratum corneum barrier layer of the skin (10,11,15,20).In this study we examined this question by measuring the penetration of ACV and idoxuridine (IDU) through excised human and guinea pig skin from three different vehicles: PEG, a modified aqueous cream (MAC), and dimethyl sulfoxide (DMSO). The results show that PEG is an inferior vehicle for the percutaneous delivery of nucleoside antiviral agents and that drug delivery is markedly enhanced by formulation in other vehicles. Skin specimens were mounted with the epidermal side up in single-chamber, jacketed diffusion cells. The temperature of the receiver chamber was controlled by circulating 37°C water through the external jacket, and the epidermal surface was left exposed to ambient conditions. Single doses of drugs were applied to the epidermal surface as either 100 pul of solution or 200 mg of ointment or cream; these quantities were sufficient to completely cover the exposed epidermal surface. MATERIALS AND METHODSDrug concentration in the receiver chamber was determined by withdrawing samples over time and measuring labeled drug by scintillation counting. Drug flux (J; in micrograms per square centimeter per hour) was calculated from the slope of a plot of drug concentration versus time, the area of the treated skin, and the volume of the receiver chamber (16).

show abstract

Section: Resultsmentioning

confidence: 99%

Failure of topical acyclovir in ointment to penetrate human skin

Freeman¹,

Sheth²,

Spruance³

1986

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The lesser release from ointment can be explained on the basis of the drug-vehicle interaction that results in a lower thermodynamic activity of the drug (13,14). Other researchers Comparison of mean cumulative amount of ACV released per unit area of mice skin through a formulation ME, control I, and control II, b formulations ME, E-1, E-2, and E-3, c formulations ME, P-1, P-2, and P-3, d formulations ME, T-1, T-2, and T-3 have suggested that the retardant effect of PEG is due to its inability to hydrate the stratum corneum or to a relative osmotic effect, which tends to dehydrate the stratum corneum (15). Microemulsions and creams show better drug release because of the penetration-enhancing properties of their components.…”

Section: Resultsmentioning

confidence: 99%

Development of Novel Microemulsion-Based Topical Formulations of Acyclovir for the Treatment of Cutaneous Herpetic Infections

2009

View full text Add to dashboard Cite

Abstract. The present investigation aims at developing microemulsion-based formulations for topical delivery of acyclovir. Various microemulsions were developed using isopropyl myristate/Captex 355/ Labrafac as an oil phase, Tween 20 as surfactant, Span 20 as cosurfactant, and water/dimethylsulfoxide (1:3) as an aqueous phase. Transcutol, eucalyptus oil, and peppermint oil were used as permeation enhancers. In vitro permeation studies through laca mice skin were performed using Franz diffusion cells. The optimum formulation containing 2.5% Transcutol as the penetration enhancer showed 1.7-fold enhancement in flux and permeation coefficient as compared to marketed cream and ointment formulation. In vivo antiviral studies were performed in female Balb/c mice against induced herpes simplex virus I infection. A single application of microemulsion formulation containing 2.5% Transcutol given 24 h post-injection resulted in complete suppression of development of herpetic skin lesions.

show abstract

“…Poor penetration of PEGs into the skin as well as their solubilizing capacities may contribute to decrease in the value of skin/base partition coefficient of substances dissolved in PEG ointments and thus decrease in skin penetration. PEGs hygroscopic properties may contribute to the stratum corneum dehydration and thus decrease in active substances penetration [32] . Moreover, PEGs are incompatible with many active substances [21] .…”

Section: Hydrophilic Basesmentioning

confidence: 99%

Dermal and Transdermal Delivery of Active Substances from Semisolid Bases

Jankowski¹,

Dyja²,

Sarecka-Hujar³

2017

pharmaceutical-sciences

View full text Add to dashboard Cite

Jankowski, et al.: Dermal and Transdermal Delivery from SemisolidsThe selection of a semisolid base type (hydrophobic, hydrophilic or emulsion) has an essential influence on the skin and transdermal delivery of active substances. The cutaneous and percutaneous absorption may be influenced by interactions occurring between base components and skin on the one hand and interactions between base components and the active ingredient on the other hand. The present article discusses the utility of different types of semisolid bases as carriers of active substances and summarizes results of studies comparing delivery of active substances from different semisolid bases.

show abstract

The influence of vehicles on skin penetration

Cited by 36 publications

References 7 publications

Failure of topical acyclovir in ointment to penetrate human skin

Failure of topical acyclovir in ointment to penetrate human skin

Development of Novel Microemulsion-Based Topical Formulations of Acyclovir for the Treatment of Cutaneous Herpetic Infections

Dermal and Transdermal Delivery of Active Substances from Semisolid Bases

Contact Info

Product

Resources

About