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Jeffrey Fudin,1– 3 Kip Vought,4 Kalpana Patel,4 Dmitri Lissin,4 Howard Maibach5 1Pain Management and PGY2 Pharmacy Pain Residency, Samuel Stratton Department of Veterans Affairs Medical Center, Albany, NY, USA; 2Remitigate Therapeutics, Delmar, NY, USA; 3Department of Pharmacy, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; 4Clinical Development, Scilex Pharmaceuticals Inc, Palo Alto, CA, USA; 5Dermatology Department, University of California San Francisco, San Francisco, CA, USACorrespondence: Dmitri Lissin, Clinical Development, Scilex Pharmaceuticals Inc, 960 San Antonio Road, Palo Alto, CA, 94303, USA, Tel +1 650.516.4310, Email dlissin@scilexpharma.comPurpose: This study evaluates and compares the clinical adhesion performance of a prescription lidocaine topical system 1.8% versus two different over-the-counter (OTC) lidocaine patches 4% and an OTC combination menthol and lidocaine patch 1%/4% in human subjects.Patients and Methods: This study was an open-label, randomized, four-treatment, four-sequence, Phase 1 adhesion performance study in healthy adult volunteers (N = 24). Lidocaine topical system 1.8% (R) and the three OTC patch products (T1, T2, and T3) were separately applied for 12 hours. Adhesion of all products was scored at 0, 3, 6, 8, and 12 hours post-application.Results: There were no issues with the conduct of the study. Overall, the majority (≥ 59.1%) of subjects treated (“patched”) with the lidocaine topical system 1.8% (R) demonstrated ≥ 90% adhesion (FDA adhesion score 0) throughout the 12-hour administration period versus 27.3% of subjects treated with OTC lidocaine patch 4% (T1), 22.7% of subjects treated with OTC lidocaine patch 4% (T2), and 18.2% of subjects treated with OTC menthol/lidocaine patch 1%/4%. Only one subject (4.5%) treated with lidocaine topical system 1.8% was observed with < 75% adhesion (FDA adhesion score < 2) versus 11 (50.0%) and 10 (45.5%) for the two OTC lidocaine patches 4% (T1 and T2), respectively, and 13 (59.1%) subjects for the OTC menthol/lidocaine patch 1%/4%. There were no complete detachments observed for lidocaine topical system 1.8%, whereas 50.0% and 31.8% complete detachments were observed for the two OTC lidocaine patches 4% (T1 and T2), and 27.3% complete detachments were observed for the OTC menthol/lidocaine patch 1%/4%. No adverse events were observed for any of the treatments.Conclusion: Lidocaine topical system 1.8% demonstrated superior adhesion relative to the three lidocaine-containing OTC products over the 12-hour treatment period.Keywords: lidocaine topical system, lidocaine patch, menthol/lidocaine patch, over-the-counter, adhesion, postherpetic neuralgia, external analgesic

Transdermal drug delivery systems (TDDS), commonly refered to as "patches", present a nonintrusive technique to provide medication without the need for invasive procedures. These products adhere to the skin and gradually release a specific dosage of medicine at a defined rate into the bloodstream. Compared with other methods of drug delivery, TDDS offer benefits such as reduced invasiveness, convenience for patients, and avoidance of the metabolic processes that occur when drugs are orally consumed. Throughout time, TDDS have been used to provide medications for various medical conditions (such as nicotine, fentanyl, nitroglycerin, and clonidine), and their potential for delivering biologics is currently being explored. This review investigates the current literature on the drug delivery efficacy of medical TDDS through the transdermal route. Additionally, the review addresses potential risks and failure modes associated with TDDS design and development as well as strategies for mitigating such risks. A thorough understanding of failure modes provides a blueprint to mitigate failure and produce high-quality efficacious therapeutics.

Poison oak-induced contact dermatitis poses a significant challenge due to its urushiol oil-induced allergic reactions. Conventional preventive measures like avoidance and post-exposure cleansing are often impractical, necessitating innovative strategies. This comprehensive review explores emerging technologies and formulations for preventing poison oak dermatitis. Literature search via PubMed and Covidence identified 13 relevant studies, with six discussing preventive measures. Barrier methods, including occlusive creams and protective clothing, showed promise in reducing dermatitis risk. Immunotherapy, although investigated, requires further development. Complete avoidance, while effective, is often impractical. The complexity of poison oak management underscores the need for ongoing research to develop more effective preventive measures. This review highlights the current landscape, identifies gaps in knowledge, and emphasizes the importance of continued research for improved prevention and management of poison oak-induced dermatitis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Machine learning (ML) offers an opportunity in contact dermatitis (CD) research, where with full clinical picture, may support diagnosis and patch test accuracy., Objective: This review aims to summarise the existing literature on how ML can be applied to CD in its entirety., Methods: Embase, Medline, IEEE Xplore, and ACM Digital Library were searched from inception to February 7, 2024, for primary literature reporting on ML models in CD., Results: 7834 articles were identified in the search, with 110 moving to full-text review, and six articles included. Two used ML to identify key biomarkers to help distinguish between allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD), three used image data to distinguish between ACD and ICD, and one used clinical and demographical data to predict the risk of positive patch tests. All studies used supervision in their ML model training with a total of 49 704 patients across all data sets. There was sparse reporting of the accuracy of these models., Conclusions: Although the available research is still limited, there is evidence to suggest that ML has potential to support diagnostic outcomes in a clinical setting. Further research on the use of ML in clinical practice is recommended., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Actinic keratosis (AK) is a common precancerous skin condition predominantly affecting older males with fair skin and significant UV exposure. The clinical significance of AK is related to its potential for malignant transformation and progression to squamous cell carcinoma (SCC). Accurate diagnosis of AK is essential for adequate treatment, evaluation of therapeutic efficacy, and mitigating the risk of developing SCC. However, clinician variability due to the subjective nature of current diagnostic tools presents significant challenges to achieving consistent and reliable AK diagnoses. Thus, there is no universally accepted standard for measuring AK.This review evaluates current methods for evaluating and diagnosing AK, focusing on clinician variability through inter- and intraobserver agreement. Eight peer-reviewed studies investigating the reliability of various approaches for AK evaluation show substantial variability in interobserver or intraobserver agreement, with most methods demonstrating only slight to moderate reliability. Some suggest that consensus discussions and simplified rating scales can modestly improve diagnostic reliability. However, remaining variability and the lack of a universally accepted standard for measuring AK underscore the need for more robust and standardized diagnostic and evaluation methods.The review emphasizes the need for improved diagnostic tools and standardized methods to enhance the accuracy and reliability of AK assessments. It also proposes applying a novel examination approach using 1,3-dihydroxyacetone (DHA) staining which may improve the visualization and identification of AK lesions. Advancements in these areas have significant potential, promising better clinical practices and patient outcomes in AK management., (© 2024. The Author(s).)

Exogenous allergens, found in cosmetic products, jewelry items, antiseptics and antibacterials, plants, and solvents, can cause clinical allergic contact Dermatitis (ACD). To help identify and discern which allergen is causing ACD, clinicians use patch tests, but they can yield false-negative results at times. Examining potential reasoning for false negatives is particularly helpful when a patient's history and physical examination strongly suggest ACD, and the patch test is negative. A strong history and physical presentation suggestive of ACD warrants additional patch testing or other methods to verify a false-negative patch test result. We conducted a literature review to compile various reasonings and solutions for false-negative patch tests in suspected ACD patients. Utilizing EMBASE, Scopus, PubMed, and Google Scholars, 49 articles were included by using search terms such as "False negative patch test" or "False-negative patch test" and "allergic contact Dermatitis," or "ACD." Common factors that led to false-negative patch test results include low allergen concentration, inadequate percutaneous penetration, technique error, immunosuppressive therapy, and ultraviolet exposure. Potential solutions include using different vehicles, concentration, increasing reading time, repeating the patch test, intradermal testing, and repeat open application testing. If a false-negative patch test is suspected, then intradermal testing can be administered to ensure the specificity of the patch test result. Considering the main contributing factors and solutions to false-negative patch tests, clinicians can accurately diagnose ACD and administer proper treatment plans.

Topical delivery systems (TDSs) enable the direct transport of analgesics into areas of localized pain and thus minimize the side effects of administration routes that rely on systemic drug distribution. For musculoskeletal pain, clinicians frequently prescribe topical products containing lidocaine or diclofenac. This study assessed whether drug delivery from a TDS into muscle tissue occurs mainly via direct diffusion or systemic transport. An investigational TDS containing 108 mg lidocaine (SP-103, 5.4% lidocaine), a commercially available TDS containing 36 mg lidocaine (ZTlido ® , 1.8% lidocaine), and a topical pain relief gel (Pennsaid ® , 2% diclofenac) were tested. Using open flow microperfusion (OFM), interstitial fluid from the dermis, subcutaneous adipose tissue (SAT), and muscle was continuously sampled to assess drug penetration in all tissue layers. Ex vivo and in vivo experiments showed a higher diffusive transport of lidocaine compared to diclofenac. The data showed a clear contribution of diffusive transport to lidocaine concentration, with SP-103 5.4% resulting in a significantly higher lidocaine concentration in muscle tissue than commercially available ZTlido ® ( p = 0.008). These results indicate that SP-103 5.4% is highly effective in delivering lidocaine into muscle tissue in areas of localized pain for the treatment of musculoskeletal pain disorders (e.g., lower back pain).

Triamcinolone acetonide is a glucocorticosteroid used in standard clinical practice for its anti-inflammatory properties. Although it can be given via different routes of administration, the intramuscular route is unique compared with other corticosteroids-its effects remain potent over a longer period of time. We summarize the existing literature on the pharmacokinetic and pharmacodynamic mechanisms of intramuscular triamcinolone acetonide (Kenalog ® ). The fascinating nature of the purported efficacy of triamcinolone acetonide may be attributed to differing binding mechanisms, low solubility in blood, a low renal clearance rate, and various metabolites and other yet defined effects on skin. The enigma of the purported efficacy of triamcinolone acetonide may lie in the fact that it has a unique nature of having a long-term effect on dermatologic disease using a seemingly low dose compared with other routes of administration and other corticosteroids. Possible reasons for this may be binding differences at the intramuscular site, low solubility due to acetonide esters, a slow rate of absorption from the injected site, and a low renal clearance rate. There is still much to be learned about its mechanism of action, which may be of clinical and therapeutic significance., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

For more than five decades, pharmaceutical manufacturers have been relying heavily on batch manufacturing that is a sequential, multistep, laborious, and time-consuming process. However, late advances in manufacturing technologies have prompted manufacturers to consider continuous manufacturing (CM) is a feasible manufacturing process that encompasses fewer steps and is less tedious and quick. Global regulatory agencies are taking a proactive role to facilitate pharmaceutical industries to adopt CM that assures product quality by employing robust manufacturing technologies encountering fewer interruptions, thereby substantially reducing product failures and recalls. However, adopting innovative CM is known to pose technical and regulatory challenges. Hot melt extrusion (HME) is one such state-of-the-art enabling technology that facilitates CM of diverse pharmaceutical dosage forms, including topical semisolids. Efforts have been made to continuously manufacture semisolids by HME integrating the principles of Quality by Design (QbD) and Quality Risk Management (QRM) and deploying Process Analytical Technologies (PAT) tools. Attempts have been made to systematically elucidate the effect of critical material attributes (CMA) and critical process parameters (CPP) on product critical quality attributes (CQA) and Quality Target Product Profiles (QTPP) deploying PAT tools. The article critically reviews the feasibility of one of the enabling technologies such as HME in CM of topical semisolids. The review highlights the benefits of the CM process and challenges ahead to implement the technology to topical semisolids. Once the CM of semisolids adopting melt extrusion integrated with PAT tools becomes a reality, the process can be extended to manufacture sterile semisolids that usually involve more critical processing steps.

Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).

We read with interest the recent publication of Dinesen et al. [...].

Skin is a detailed, organized, and intricate niche in the human body. Topical and transdermal drugs are unique, in that their absorption is quite different from other routes of administration (oral, intramuscular, intravenous, etc.,.). A robust amount of research is required to approve the use of a drug- in vivo , in vitro , and ex vivo studies collectively help manufacturers and government agencies with approval of various compounds. Use of human and animal studies poses ethical and financial concerns, making samples difficult to use. In vitro and ex vivo methods have improved over the past several decades-results show relevance when compared to in vivo methods. The history of testing is discussed, followed by a detailed account of known complexities of skin and the current state of percutaneous penetration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shahinfar and Maibach.)

The objective of the project was to investigate the plausibility of active pharmaceutical ingredients (APIs) to undergo sublimation from topical application following evaporation of solvent. Topical formulations with different APIs were subjected to a sublimation screening test. The APIs in the selected topical products were found to undergo sublimation to a different extent. The salicylic acid topical product was found to undergo a significant loss due to sublimation. The extent of sublimation of salicylic acid was significantly greater at skin temperature compared to room temperature. When the APIs were subjected to the sublimation screening test in their neat form at 32 ± 1 °C, the natural log of the rate of sublimation decreased linearly with the standard enthalpy of sublimation of compound ( R 2 = 0.89). The formulation composition was found to have a significant impact on the extent of sublimation of the representative API, salicylic acid. The sublimation of APIs from the topical product was found to affect the mass balance studies in the case of the salicylic acid ointment. Furthermore, the results of the human studies agreed with the in vitro experimental results demonstrating the plausibility of loss of API due to sublimation from the site of application.

Microneedles (MNs) are needles with a tip diameter ranging from 10 to 100 um and a length ranging up to 1 mm. The first patent for drug delivery device for percutaneous administration filed by Alza corporation dates back to 1976 (Gerstel and Place, 1976), and in between 1989 and 2021 the filed patents for MNs are >4500 [1]. These devices can potential overcome some drawbacks of traditional needles, such as the pain generated during insertion, requirement for trained personnel to manipulate syringes, and difficulty of performing injections in elderly and obese patients. MNs and MN arrays are emerging as a convenient method to deliver compounds and extract blood without causing any pain. A promising application is the use of MNs as alternative solution to topical creams (TC) and transdermal patches (TP) for transdermal drug delivery. The external layer of human skin, the epidermis, offers a major barrier to transdermal drug delivery, thanks to the stratum corneum (SC). Exposed to the external environment, SC ultimately protects the human body from UV light radiation, heat, water loss, bacteria, fungi and viruses, and it is the barrier that controls diffusion rate for almost all compounds. TC and TP applications are limited by the skin permeability to lipophilic compounds and small molecules, and by the slow delivery rate of some compounds. MNs have been around for >35 year now, and it is a general opinion that MNs increase delivery compared to passive diffusion, thanks to the feature of penetrating the SC and reaching the dermis. This review recollects the existing studies that compare MN delivery of drugs with passive diffusion of the same drugs in alive organisms, giving an overview of what are the type of MNs, the chemical delivered and the methods employed to quantify drug delivery into skin and/or in the bloodstream. The final aim is to quantify the enhancement factor of MNs with respect to passive diffusion, and establish a possible standard on how tests can be performed in order to compare different data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Allergic contact dermatitis (ACD) remains a public health issue worldwide, despite regulations intended to minimize sensitization. With up-to-date knowledge about which chemicals continue to have high allergenicity, the government/industry can refocus their efforts to be most effective. Objective: We reviewed updated data showing common allergens that elicit ACD to determine the progress in reducing sensitization to inform public health policy, government regulation, and industry standards. Methods: We compiled data from the North American Contact Dermatitis Group showing patch test results from 1984 to 2016 for 153 compounds. Using these data, we analyzed the trends over time of positive test reactions to determine whether they are increasing or decreasing. Results: Of the 47 compounds with sufficient data to analyze, 23 had a decreasing proportion of positive patch test results over the whole period. An additional 5 had a decreasing proportion over a shorter period. Finally, 4 had an increasing proportion over any period: compositae mix, methylchloroisothiazolinone/methylisothiazolinone, nickel sulfate, and thimerosal mix. Conclusions: The data strongly indicate decreasing and increasing frequency trends and challenge us to seek explanations, which are not yet clear. It is hoped that these data can be valuable in informing public health policy, government, and industry.

Polymeric microneedles were prepared with Polyvinyl Pyrrolidone (PVP) K-30 using the mold casting technique. The core microneedles were coated with Eudragit E-100 by dip and spin method. The amount of 5-fluorouracil (FU) loaded in the core microneedles was 604 ± 35.4 µg. The coating thickness was 24.12 ± 1.12 µm. The objective was to deliver the 5-FU gradually in a controlled release manner at the target site in the sub-stratum corneum layer. This approach is anticipated to improve the safety and efficacy of topical melanoma treatment. The release of the drug was prolonged for up to 3 h from the polymer-coated polymeric (PCP) microneedles. The entire amount was found to release within 15 min in uncoated MNs. Likewise, the permeation of the drug from the uncoated microneedles was rapid, whereas the PCP microneedles were able to prolong the permeation up to 420 min. The PCP microneedles were subjected to stability studies at 25°C ± 2°C/60%RH, and 40°C ± 2°C/75%RH condition for 3 months. The formulations were found intact, and the release rate was not significantly different form the fresh formulation. The drug content was found to meet the acceptability criteria as well (98.12 ± 1.8% and 97.8 ± 2.1% at 25 and 40°C respectively after 3 months). Overall, this study demonstrated the feasibility of fabrication of PCP microneedles using Eudragit E100 for intraregional controlled delivery of drugs., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Introduction: The accumulation of tissue-advanced glycation end products in skin results from complex and consecutive reactions and can be measured by skin autofluorescence (SAF) reader devices. This overview discusses studies evaluating the utilization of SAF in screening renal and cardiac disease., Materials and Methods: Literature search was performed using Google Scholar, PubMed, Springer, Ovid, and ScienceDirect., Results: SAF was an independent predictor of progression of chronic kidney disease (CKD) and was elevated in subjects on hemodialysis and peritoneal dialysis. Furthermore, SAF was significantly associated with cardiovascular events, cardiovascular mortality, and all-cause mortality in CKD patients. Other studies revealed a correlation between SAF and arterial stiffness, vascular damage, and subclinical atherosclerosis. A vegetarian diet was associated with lower SAF levels, whereas malnutrition was correlated with higher levels and increased mortality., Conclusions: SAF measurement may be useful in managing renal and cardiac disease. Future studies are needed to clarify the specific role of SAF in the management of CKD and its noninvasive office utilization to identify comorbidities in inflammatory diseases, such as psoriasis., (© 2022 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Mohs micrographic surgery (MMS) is considered the gold standard treatment for skin cancers. Though the high cure rates it offers, MMS presents some disadvantages, as it is a relatively time-consuming procedure involving several professionals (physicians and technicians). A better definition of tumor margins in the preoperative setting with any optical noninvasive diagnostic method may reduce the numbers of MMS steps and the overall duration of the procedure. The present review was conducted and reported using validated search strategies from the following databases: PUBMED and Ovid MEDLINE. Our review describes the use of procedures such as dermoscopy, optical coherence tomography, reflectance confocal microscopy and fluorescent confocal microscopy to determine tumor extension in the preoperative setting of Mohs surgery for the treatment of skin cancers. Presurgical margin assessment with noninvasive diagnostic techniques seem to provide a benefit in the patients' management, especially for tumors located in critical areas with a high risk of recurrence. The use is limited to the high costs and limited availability of new technologies., (© 2022 Wiley Periodicals LLC.)

Background: Allergic contact dermatitis (ACD) remains a public health issue worldwide, despite regulations intended to minimize sensitization. With up-to-date knowledge about which chemicals continue to have high allergenicity, the government/industry can refocus their efforts to be most effective., Objective: We reviewed updated data showing common allergens that elicit ACD to determine the progress in reducing sensitization to inform public health policy, government regulation, and industry standards., Methods: We compiled data from the North American Contact Dermatitis Group showing patch test results from 1984 to 2016 for 153 compounds. Using these data, we analyzed the trends over time of positive test reactions to determine whether they are increasing or decreasing., Results: Of the 47 compounds with sufficient data to analyze, 23 had a decreasing proportion of positive patch test results over the whole period. An additional 5 had a decreasing proportion over a shorter period. Finally, 4 had an increasing proportion over any period: compositae mix, methylchloroisothiazolinone/methylisothiazolinone, nickel sulfate, and thimerosal mix., Conclusions: The data strongly indicate decreasing and increasing frequency trends and challenge us to seek explanations, which are not yet clear. It is hoped that these data can be valuable in informing public health policy, government, and industry., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2022 American Contact Dermatitis Society. All Rights Reserved.)

The Polymer Coated Polymeric (PCP) microneedles were fabricated using PVP K30 in the core and ethyl cellulose in the coating. The PCP microneedles do not disintegrate in the tissue upon insertion and rather stays intact and allows diffusion of drugs and analytes across the membrane both inward and outward. In this project the potential use of PCP microneedles for sampling analytes from the dermal tissue was explored. The amount of analyte sampled depended on the concentration in the tissue, physicochemical properties of the analyte and duration of insertion of the array in the tissue. Further, an advanced type of PCP microneedle array was fabricated by entrapping absorbent beads in the core microneedles. The adsorbent enabled the PCP microneedles to recover significantly higher amount of analyte from the tissue., (Copyright © 2022. Published by Elsevier B.V.)

Physicochemical and formulation factors influencing penetration of drugs from topical products into the skin and mechanisms of drug permeation are well investigated and reported in the literature. However, mechanisms of drug absorption during short-term exposure have not been given sufficient importance. In this project, the extent of absorption of drug molecules into the skin from aqueous and ethanolic solutions following a 5-min application period was investigated. The experiments demonstrated measurable magnitude of absorption into the skin for all the molecules tested despite the duration of exposure being only few minutes. Among the two solvents used, absorption was greater from aqueous than ethanolic solution. The results suggest that an alternative penetration pathway, herein referred to as the convective transport pathway, is likely responsible for the rapid, significant uptake of drug molecules during initial few minutes of exposure. Additionally, absorption through the convective transport pathways is a function of the physicochemical nature of the formulation vehicle rather than the API., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Introduction: Skin care products are often utilized in conjunction with topical treatment for skin disease. However, these appears insufficient body of experimental data to advise the health care worker or patient. Examine penetration effect (hence potential for altering efficacy and toxicity) - dosing with one topical after another and how quickly such a potential phenomenon might occur., Methods: A marketed moisturizer applied on human skin with an in vitro diffusion system. At 1, 15, and 30 min post application, [ 14 C]-benzoic acid dosed the same skin site for 24 h. Amounts of chemical retained in skin and permeation flux rats were measured to determine penetration effect of the prior moisturizer application., Results: Exposure of a water-enriched moisturizer before a hydrophilic chemical immediate application favors the chemical penetration, especial in 1 and 15 min moisturizer exposure groups. The enhancement effect was expressed as an earlier lag time and a rapid absorption peak when compared to related non-moisturizer control., Conclusion: This experiment opens up a large door: what would be the result with many complex topical products and different tracers was used here, of varying hydrophilicity and lipophilicity. We do not wish to overgeneralize until such studies are confirmed in vivo .

Background: The process by which drugs leave the bloodstream to enter the skin compartments is important in determining appropriate routes of delivery and developing more efficacious medications. We conducted a general literature review on percutaneous egression mechanisms., Summary: Studies demonstrate that the stratum corneum (SC) is a compartment for systemically delivered drugs. Upon reviewing the available literature, it became apparent that there may be multiple mechanisms of percutaneous egression dependent upon drug physiochemical properties. These mechanisms include, but are not limited to, desquamation, sebum secretion, sweat transport, and passive diffusion. While drugs often utilize one major pathway, it is possible that all mechanisms may play a role to varying extents., Key Messages: Available literature suggests that hydrophilic substances tended to travel from blood to the upper layers of the skin via sweat, whereas lipophilic substances utilized sebum secretion to reach the SC. Upon reaching the skin surface, the drugs spread laterally before penetrating back into the skin as if they were topically administered. More data are warranted to identify additional percutaneous egression mechanisms, precise drug action sites, and accelerate drug development., (© 2022 The Author(s). Published by S. Karger AG, Basel.)