Effects of permeation enhancers on flufenamic acid delivery in Ex vivo human skin by confocal Raman microscopy

Pyatski, Yelena; Zhang, Qihong; Mendelsohn, Richard; Flach, Carol R.

doi:10.1016/j.ijpharm.2016.04.011

Cited by 31 publications

(19 citation statements)

References 40 publications

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“…Finally, the ex vivo experiment offers additional advantages as are evident in the 2D images shown in Figure . The ability to image various spectral parameters allows examination of endogenous molecular structure changes related to barrier function (eg, lipid order and packing) and keratin secondary structure, among others . In addition, the ability to monitor the source of hydration as resolved in the “D 2 O underneath” experiment described herein, not possible for an in vivo measurement, provides unique information regarding mechanisms of hydration.…”

Section: Discussionmentioning

confidence: 99%

“…A section of human abdominal skin (~1.5 cm 2 ) was assembled in a home‐built brass cell equipped with a water‐filled hydration chamber underneath the dermis. Details of the cell have been described previously . Approximately 25 μL of D 2 O was applied in the middle of the skin surface, and the cell was sealed with parafilm to maintain hydration.…”

Section: Methodsmentioning

confidence: 99%

“…Since the early 2000s, CRM has evolved as an important, noninvasive approach providing skin hydration levels and penetration profiles of topically applied exogenous agents. [10][11][12][13][14][15][16] In addition, the spatially resolved molecular structure information inherent in the Raman spectra yield insight into penetration and hydration mechanisms. [16][17][18] For a review of confocal Raman microscopy applications related to drug delivery systems see Smith, et al 2015 19 and references therein.…”

Section: Introductionmentioning

confidence: 99%

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Novel confocal Raman microscopy method to investigate hydration mechanisms in human skin

Wang

Zhang

Mao

et al. 2019

Skin Research and Technology

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Background Skin hydration is essential for maintaining stratum corneum (SC) flexibility and facilitating maturation events. Moisturizers contain multiple ingredients to maintain and improve skin hydration although a complete understanding of hydration mechanisms is lacking. The ability to differentiate the source of the hydration (water from the environment or deeper skin regions) upon application of product will aid in designing more efficacious formulations. Materials and Methods Novel confocal Raman microscopy (CRM) experiments allow us to investigate mechanisms and levels of hydration in the SC. Using deuterium oxide (D2O) as a probe permits the differentiation of endogenous water (H2O) from exogenous D2O. Following topical application of D2O, we first compare in vivo skin depth profiles with those obtained using ex vivo skin. Additional ex vivo experiments are conducted to quantify the kinetics of D2O diffusion in the epidermis by introducing D2O under the dermis. Results Relative D2O depth profiles from in vivo and ex vivo measurements compare well considering procedural and instrumental differences. Additional in vivo experiments where D2O was applied following topical glycerin application increased the longevity of D2O in the SC. Reproducible rates of D2O diffusion as a function of depth have been established for experiments where D2O is introduced under ex vivo skin. Conclusion Unique information regarding hydration mechanisms are obtained from CRM experiments using D2O as a probe. The source and relative rates of hydration can be delineated using ex vivo skin with D2O underneath. One can envision comparing these depth‐dependent rates in the presence and absence of topically applied hydrating agents to obtain mechanistic information.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel confocal Raman microscopy method to investigate hydration mechanisms in human skin

Wang

Zhang

Mao

et al. 2019

Skin Research and Technology

Self Cite

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show abstract

“…The model we developed successfully shows that it is possible to detect significant differences between two formulations regarding the penetration depth and kinetics of a drug. Understanding the effects of penetration enhancers is important in the development of topically applied formulation, in pharmaceutics, as well as in cosmetics [ 35 ]. In particular, in comparative studies between two formulations, the developed method is a promising, time- and resources-saving alternative to the destructive conventional methods.…”

Section: Discussionmentioning

confidence: 99%

A New Method for In-Situ Skin Penetration Analysis by Confocal Raman Microscopy

Krombholz

Lunter

2020

Molecules

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In the development of dermal drug formulations and cosmetics, understanding the penetration properties of the active ingredients is crucial. Given that widespread methods, including tape stripping, lack in spatial resolution, while being time- and labour-intensive, Confocal Raman Microscopy is a promising alternative. In optimizing topically applied formulations, or the development of generic formulations, comparative in-situ measurements have a huge potential of saving time and resources. In this work, we show our approach to in-situ skin penetration analysis by confocal Raman Microscopy. To analyse feasibility of the approach, we used caffeine solutions as model vehicles and tested the effectiveness of 1,2-pentanediol as a penetration enhancer for delivery to the skin.

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“…In addition, it is good for following up the penetration/permeation of APIs [114,115]. Nowadays, Raman microscopy is a powerful technique to properly understand skin structure and percutaneous drug delivery [111,[116][117][118].…”

Section: Confocal Raman Microscopic Methodsmentioning

confidence: 99%

Methods to Evaluate Skin Penetration In Vitro

et al. 2019

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Dermal and transdermal drug therapy is increasing in importance nowadays in drug development. To completely utilize the potential of this administration route, it is necessary to optimize the drug release and skin penetration measurements. This review covers the most well-known and up-to-date methods for evaluating the cutaneous penetration of drugs in vitro as a supporting tool for pharmaceutical research scientists in the early stage of drug development. The aim of this article is to present various experimental models used in dermal/transdermal research and summarize the novel knowledge about the main in vitro methods available to study skin penetration. These techniques are: Diffusion cell, skin-PAMPA, tape stripping, two-photon microscopy, confocal laser scanning microscopy, and confocal Raman microscopic method.

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Effects of permeation enhancers on flufenamic acid delivery in Ex vivo human skin by confocal Raman microscopy

Cited by 31 publications

References 40 publications

Novel confocal Raman microscopy method to investigate hydration mechanisms in human skin

Novel confocal Raman microscopy method to investigate hydration mechanisms in human skin

A New Method for In-Situ Skin Penetration Analysis by Confocal Raman Microscopy

Methods to Evaluate Skin Penetration In Vitro

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