Predicting topical drug clearance from the skin

Tabosa, Maria Alice Maciel; Hoppel, Magdalena; Bunge, Annette L.; Guy, Richard H.; Delgado‐Charro, M. Begoña

doi:10.1007/s13346-020-00864-8

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…The penetration of the active compound might be slow, creating challenges in reaching the desired concentration [121]. Determining the concentration of the compound within the skin layers, as well as determining the compound clearance and degradation from these layers, is challenging as well as [122].…”

Section: Challenges Of Antimicrobial Treatment and Delivery To The Skinmentioning

confidence: 99%

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

2021

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Chitosan is one of the most studied natural origin polymers for biomedical applications. This review focuses on the potential of chitosan in localized antimicrobial therapy to address the challenges of current rising antimicrobial resistance. Due to its mucoadhesiveness, chitosan offers the opportunity to prolong the formulation residence time at mucosal sites; its wound healing properties open possibilities to utilize chitosan as wound dressings with multitargeted activities and more. We provide an unbiased overview of the state-of-the-art chitosan-based delivery systems categorized by the administration site, addressing the site-related challenges and evaluating the representative formulations. Specifically, we offer an in-depth analysis of the current challenges of the chitosan-based novel delivery systems for skin and vaginal infections, including its formulations optimizations and limitations. A brief overview of chitosan’s potential in treating ocular, buccal and dental, and nasal infections is included. We close the review with remarks on toxicity issues and remaining challenges and perspectives.

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Section: Challenges Of Antimicrobial Treatment and Delivery To The Skinmentioning

confidence: 99%

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

2021

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“…Of course, the 'input' function only provides part of the information needed to estimate a drug's concentration in the sub-SC compartment and that requires knowledge of the local clearance too (and may be even more complicated for drugs subject to epidermal metabolism). However, there are models and associated algorithms for estimating 'dermal clearance' by the local microcirculation (10,11) and these can be used, together with the delivery rate of drug from SC obtained from tape-stripping experiments, to calculate a concentration in a viable skin compartment-the C* value as described by Higuchi et al many years ago (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Assessment of Drug Delivery Kinetics to Epidermal Targets In Vivo

Hoppel

Tabosa

Bunge

et al. 2021

AAPS J

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It has proven challenging to quantify ‘drug input’ from a formulation to the viable skin because the epidermal and dermal targets of topically applied drugs are difficult, if not impossible, to access in vivo. Defining the drug input function to the viable skin with a straightforward and practical experimental approach would enable a key component of dermal pharmacokinetics to be characterised. It has been hypothesised that measuring drug uptake into and clearance from the stratum corneum (SC) by tape-stripping allows estimation of a topical drug’s input function into the viable tissue. This study aimed to test this idea by determining the input of nicotine and lidocaine into the viable skin, following the application of commercialised transdermal patches to healthy human volunteers. The known input rates of these delivery systems were used to validate and assess the results from the tape-stripping protocol. The drug input rates from in vivo tape-stripping agreed well with the claimed delivery rates of the patches. The experimental approach was then used to determine the input of lidocaine from a marketed cream, a typical topical product for which the amount of drug absorbed has not been well-characterised. A significantly higher delivery of lidocaine from the cream than from the patch was found. The different input rates between drugs and formulations in vivo were confirmed qualitatively and quantitatively in vitro in conventional diffusion cells using dermatomed abdominal pig skin.

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“…# The 5 mg cm −2 value is significantly greater (p < 0.05) than that for 2 mg cm −2 from the applied product, an essential element to creating a predictive model of dermatopharmacokinetics. Such a capability would then be combined with information on drug clearance from the skin [5][6][7][8]13] to provide a tool with which to optimise a formulation and maximise the residence time of the active at its therapeutic target. Table 2 Power analysis and sample size calculations for both SC sampling uptake (Q Up ) and clearance (Q Cl ) and SB (AAEC 0-22 h) metrics.…”

Section: Discussionmentioning

confidence: 99%

“…The study was approved by the Research Ethics Approval Committee for Health at the University of Bath (REACH EP 17/18 154). Informed consent All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all subjects for being included in the study.…”

Section: Availability Of Data and Materialsmentioning

confidence: 99%

“…The latter reflects the balance between the drug's rate and extent of absorption from a given formulation to the site of action (i.e. the input function) and its clearance from the target site, for example, into the systemic circulation [5][6][7][8]. For topical corticosteroids, the input process comprises release from the applied formulation, partitioning into the stratum corneum (SC) and diffusion through the barrier to reach the viable epidermis and dermis where the target glucocorticoid receptors are located [9,10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of dermal bioavailability: predicting the input function for topical glucocorticoids using stratum corneum sampling

Pensado

McGrogan

White

et al. 2021

Drug Deliv. and Transl. Res.

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Predicting the dermal bioavailability of topically delivered drugs is challenging. In this work, minimally invasive stratum corneum (SC) sampling was used to quantify the delivery of betamethasone valerate (BMV) into the viable skin. Betnovate® cream (0.1% w/w BMV) was applied at three doses (2, 5, and 10 mg cm−2) to the ventral forearms of 12 healthy volunteers. The mass of drug in the SC was measured using a validated tape-stripping method (a) after a 4-h “uptake” period, and (b) following a 6-h “clearance” period subsequent to cream removal. Concomitantly, the skin blanching responses to the same doses were assessed with a chromameter over 22 h post-application. BMV uptake into the SC was significantly higher for the 5 mg cm−2 dose compared to those of 2 and 10 mg cm−2. In all cases, ~30% of the drug in the SC at the end of the uptake period was cleared in the subsequent 6 h. From the SC sampling data, the average drug flux into the viable epidermis and its first-order elimination rate constant from the SC were estimated as 4 ng cm−2 h−1 and 0.07 h−1, respectively. In contrast, skin blanching results were highly variable and insensitive to the dose of cream applied. The SC sampling method was able to detect a 50% difference between two applied doses with 80% power; detection of a 20% difference would require a larger sample size. SC sampling enabled quantitative metrics describing corticosteroid delivery to the viable epidermis to be determined. Graphical abstract

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Predicting topical drug clearance from the skin

Cited by 17 publications

References 34 publications

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

Assessment of Drug Delivery Kinetics to Epidermal Targets In Vivo

Assessment of dermal bioavailability: predicting the input function for topical glucocorticoids using stratum corneum sampling

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