Correlation of in vivo topical efficacies with in vitro predictions using acyclovir formulations in the treatment of cutaneous HSV-1 infections in hairless mice: an evaluation of the predictive value of the C∗ concept

Patel, Phenil J.; Ghanem, Abdel‐Halim; Higuchi, William I.; Srinivasan, Venkat; Kern, Earl R.

doi:10.1016/0166-3542(96)80225-7

Cited by 13 publications

(15 citation statements)

References 7 publications

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“…Flux determination was carried out after applying a fresh dose of the formulation as described earlier. 5 The samples were analyzed by reversed-phase HPLC without further preparation. The mobile phase consisted of 0.5% acetic acid.…”

Section: Methodsmentioning

confidence: 99%

“…The procedure was a slight modification of that described earlier. 4,5 Briefly, the skin over the spleen region of anesthetized animals was slightly abraded with a roto-tool (MotoTool, model 395; Dremel, WI) on the first day of the experiment. The roto-tool allowed a better control over the length and depth of the skin abrasion compared with the needle used in earlier method.…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3][4][5] The parameter C* was proposed to be a true measure of the in vivo efficacy of a topical formualtion. We have used acyclovir (ACV) as a model drug in the treatment of cutaneous herpes simplex virus type 1 (HSV-1) infections in hairless mice to develop and substantiate this concept.…”

Section: Introductionmentioning

confidence: 99%

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Relationship of Skin Target Site Free Drug Concentration (C) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C Concept Using Acyclovir as a Model Drug

Mehta

Afouna

Ghanem

et al. 1997

Journal of Pharmaceutical Sciences

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For the past few years, our laboratory has been involved in the development of a novel approach for predicting topical in vivo efficacy based on the estimation of skin target site free drug concentration (C*) from in vitro flux data. We have used acyclovir (ACV) as a model drug in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice. The goal of this study was to rigorously evaluate the applicability of this approach over the entire range of topical efficacy (i.e., from 0 to 100%). We employed a variety of ACV formulations differing in solvent compositions, enhancers, and excipients (and therefore in their efficacies) to achieve this goal. The C* values were estimated from the in vitro flux data obtained in an in vivo-in vitro experimental design that closely approximated the in vivo treatment protocol. For the in vivo antiviral efficacy studies, a finite dose of ACV formulation was applied twice a day, beginning the day after virus inoculation, for 4 days. The lesions were scored on the fifth day, and the efficacies were calculated as described earlier. Our results indicate that, for a variety of formulations over a wide range of efficacies, the predictions based on C* are in good agreement with the observed in vivo efficacies. These findings strongly demonstrate the predictive value of C* over the entire range of topical efficacy, thereby further strengthening its potential for future studies. The findings also indicate that although the excipients in a formulation may alter the rate and extent of available drug at the target site, in these cases, they do not seem to have any effect on the in vivo potency of the drug.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Relationship of Skin Target Site Free Drug Concentration (C) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C Concept Using Acyclovir as a Model Drug

Mehta

Afouna

Ghanem

et al. 1997

Journal of Pharmaceutical Sciences

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“…Different from transdermal delivery, the viable epidermis is the target site in most topical drug delivery, and the drug concentration in this tissue layer is related not only to the flux but the dermis barrier. As can be seen in figure 4, the concentration in the viable epidermal layer C * (defined as the free drug concentration in the basal cell layer of the epidermis) is affected by the dermis [35]:…”

Section: Influence Of the Dermis Layer On Target Skin Concentration C*mentioning

confidence: 99%

“…Thus, drug concentration at the target site is difficult to measure in topical drug delivery. The concept of using C * to evaluate topical drug delivery was previously examined with antiviral drugs such as acyclovir, deoxyuridine, and cidofovir in test formulations in a hairless mouse model for the treatment of cutaneous herpes simplex virus type-1 infections [35,36,37]. In these studies, the in vivo antiviral efficacies were measured and compared with C * measured in an in vivo/in vitro experimental design that approximated the in vivo antiviral treatment protocol.…”

Section: Influence Of the Dermis Layer On Target Skin Concentration C*mentioning

confidence: 99%

Passive and Iontophoretic Transport through the Skin Polar Pathway

Peck

2013

Skin Pharmacol Physiol

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The purpose of the present article is to briefly recount the contributions of Prof. William I. Higuchi to the area of skin transport. These contributions include developing fundamental knowledge of the barrier properties of the stratum corneum, mechanisms of skin transport, concentration gradient across skin in topical drug applications that target the viable epidermal layer, and permeation enhancement by chemical and electrical means. The complex and changeable nature of the skin barrier makes it difficult to assess and characterize the critical parameters that influence skin permeation. The systematic and mechanistic approaches taken by Dr. Higuchi in studying these parameters provided fundamental knowledge in this area and had a measured and lasting influence upon this field of study. This article specifically reviews the validation and characterization of the polar permeation pathway, the mechanistic model of skin transport, the influence of the dermis on the target skin concentration concept, and iontophoretic transport across the polar pathway of skin including the effects of electroosmosis and electropermeabilization.

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Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery

Mohammed

Moghimi

Yousef

et al. 2017

Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin

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Correlation of in vivo topical efficacies with in vitro predictions using acyclovir formulations in the treatment of cutaneous HSV-1 infections in hairless mice: an evaluation of the predictive value of the C∗ concept

Cited by 13 publications

References 7 publications

Relationship of Skin Target Site Free Drug Concentration (C) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C Concept Using Acyclovir as a Model Drug

Relationship of Skin Target Site Free Drug Concentration (C) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C Concept Using Acyclovir as a Model Drug

Passive and Iontophoretic Transport through the Skin Polar Pathway

Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery

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Correlation of in vivo topical efficacies with in vitro predictions using acyclovir formulations in the treatment of cutaneous HSV-1 infections in hairless mice: an evaluation of the predictive value of the C∗ concept

Cited by 13 publications

References 7 publications

Relationship of Skin Target Site Free Drug Concentration (C*) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C* Concept Using Acyclovir as a Model Drug

Relationship of Skin Target Site Free Drug Concentration (C*) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C* Concept Using Acyclovir as a Model Drug

Passive and Iontophoretic Transport through the Skin Polar Pathway

Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery

Contact Info

Product

Resources

About

Relationship of Skin Target Site Free Drug Concentration (C) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C Concept Using Acyclovir as a Model Drug

Relationship of Skin Target Site Free Drug Concentration (C) to the In Vivo Efficacy: An Extensive Evaluation of the Predictive Value of the C Concept Using Acyclovir as a Model Drug