Transdermal Drug Delivery Systems (TDDS): Recent Advances and Failure Modes.

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.

Diagnosing contact dermatitis using machine learning: A review.

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.

Can Continuous Manufacturing of Topical Semisolids by Hot Melt Extrusion Soon Be a Reality?

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.

Sublimation of Drugs from the Site of Application of Topical Products.

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 (R2 = 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.

Medical school dermatology education: a scoping review.

Dermatological diseases are widespread and have a significant impact on the quality of life of patients; however, access to appropriate care is often limited. Improved early training during medical school represents a potential upstream solution. This scoping review explores dermatology education during medical school, with a focus on identifying the factors associated with optimizing the preparation of future physicians to provide care for patients with skin disease. A literature search was conducted using online databases (Embase, MEDLINE, CINAHL and Scopus) to identify relevant studies. The Joanna Briggs Institute methodological framework for scoping reviews was used, including quantitative and qualitative data analysis following a grounded theory approach. From 1490 articles identified, 376 articles were included. Most studies were from the USA (46.3%), UK (16.2%), Germany (6.4%) and Canada (5.6%). Only 46.8% were published as original articles, with a relatively large proportion either as letters (29.2%) or abstracts (12.2%). Literature was grouped into three themes: teaching content, delivery and assessment. Core learning objectives were country dependent; however, a common thread was the importance of skin cancer teaching and recognition that diversity and cultural competence need greater fostering. Various methods of delivery and assessment were identified, including computer-aided and online, audiovisual, clinical immersion, didactic, simulation and peer-led approaches. The advantages and disadvantages of each need to be weighed when deciding which is most appropriate for a given learning outcome. The broader teaching-learning ecosystem is influenced by (i) community health needs and medical school resources, and (ii) the student and their ability to learn and perform. Efforts to optimize dermatology education may use this review to further investigate and adapt teaching according to local needs and context.

Prevalence and trend of allergen sensitization in patients with cheilitis referred for patch testing, North American Contact Dermatitis Group data, 2001-2018.

BACKGROUND: An updated understanding of allergic contact cheilitis is needed. OBJECTIVES: To characterize clinical characteristics and allergen relevance in patients with cheilitis referred for patch testing. METHODS: Retrospective analysis of 43 772 patients patch tested with the North American Contact Dermatitis Group (NACDG) screening series from 2001 to 2018. RESULTS: Overall, 2094 patients (4.8%) had lips as one of three sites of dermatitis, 1583 (3.6%) had lips as the primary site and 1167 (2.7%) had lips as the sole site of dermatitis. Prevalences of cheilitis at any, primary, and sole sites significantly increased throughout the study cycle from 2001-2002 (2.7%, 2.2% and 1.7%) to 2017-2018 (7.8%, 5.2% and 3.7%). Approximately 60% of patients with any, a primary, or a sole site of cheilitis had one or more positive allergic patch-test reactions compared to 65% of those without cheilitis. CONCLUSION: Patients with cheilitis who were referred for patch testing had high rates of positive and relevant allergens. More than one in four patients with any, primary, or sole cheilitis had a positive reaction to non-NACDG screening allergens (28.0%, 26.8%, 31.1% vs. 21.6%) compared to patients without cheilitis, emphasizing the need for expanded patch test series in cheilitis.

"Normal" TEWL-how can it be defined? A systematic review.

Trans-epidermal water loss (TEWL), the total non-eccrine sweat water evaporating from a given area of epidermis over time, is a measurement of skin barrier integrity. Skin diseases (e.g., psoriasis and atopic dermatitis) often result in transient increases in TEWL, so, knowledge of "normal" TEWL values may be used to predict disease progression in dermatological settings. Variables such as age, race and anatomic location have been suggested to affect TEWL, but current regulatory agencies have failed to control for additional variables of interest. Thus, this review summarizes variables that may cause TEWL variation. A comprehensive literature search was performed using Embase, PubMed and Web of Science to find human studies that provided data on variables affecting TEWL. 31 studies, analysing 22 affecting TEWL, were identified. Variables causing increased TEWL were mask-use (n = 1), dry eye disease (n = 1), chronic venous disease (n = 1), coronary artery disease (n = 1), age (infants vs adults) (n = 4), nourishment in infants (n = 1), stress within individuals (n = 2), Body Mass Index (n = 2), bathing versus showering (n = 2) and scratching/friction (n = 1). Variables with decreases in TEWL were genetic variability with SNPs on chromosome 9q34.3 (n = 1) and cancer-cachexia (n = 1). We summarized 12 variables that impact TEWL and are not typically controlled for in experimental settings. Therefore, defining normal TEWL may currently be problematic. Thus, regulatory agencies should provide stricter guidelines on proper measurement of TEWL to minimize human introduced TEWL variation, and we should continue to examine factors impacting individual skin integrity.

Regional variation in percutaneous absorption in in vitro human models: a systematic review.

Percutaneous absorption is of importance given its role in topical medicaments, transdermal drug systems, and dermatotoxicology. Many factors influence percutaneous penetration, including anatomical region, although little is currently known regarding this parameter. Hence, the aim of this study was to summarize existing data on regional variation in percutaneous penetration in in vitro human models. PubMed, Embase, Web of Science, and US patent literature were explored, and relevant data collected. Eight eligible articles were identified, which together, explored 15 anatomical locations. Four investigations compared percutaneous penetration between scalp and abdominal skin, and all concluded that the former was more permeable. Within those four studies, 10 penetrants of varying physical/chemical properties were tested indicating that in those particular study conditions, anatomical location exerted a greater effect on percutaneous absorption than the physicochemical properties of the penetrants. In addition, torso area was less absorptive than scrotum in both studies in which these sites were compared. In conclusion, the scrotum and scalp appear to be highly susceptible to percutaneous absorption compared to other locations such as the abdomen. This is postulated to be largely due to the high density of hair follicles in these areas, enabling greater penetration via the appendageal pathway. However, there is a paucity of conclusive data regarding the penetrability of other anatomical locations. Investigations testing and ranking the susceptibility of different anatomical regions is of vital importance given the importance of (1) transdermal drug delivery and decontamination protocols and (2) understanding the underlying mechanisms and degree of these variances might aid our pharmacologic/toxicologic judgments.

Hand and foot dermatitis in patients referred for patch testing: Analysis of North American Contact Dermatitis Group Data, 2001-2018.

BACKGROUND: Dermatitis localized to hands (HD), feet (FD), or both hands and feet (HFD) has multiple etiologies, including atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis. Unfortunately, little is known about clinical differences between patients with HD, FD, and HFD. OBJECTIVE: To characterize differences in demographics, etiology, and patch testing results among patients presenting with HD, FD, or HFD referred for patch testing. METHODS: A retrospective analysis of patients patch tested by the North American Contact Dermatitis Group between 2001 and 2018. RESULTS: Of 43,677 patients who were patch tested, 22.8% had HD, 2.9% had FD, and 3.7% had HFD. Allergic and currently relevant patch test reactions to ≥1 North American Contact Dermatitis Group screening allergen occurred in similar proportions in all 3 study groups. However, HD (18.0%) had higher proportions of occupationally relevant reactions than HFD (8.9%) or FD (4.0%). Nickel and fragrance mix I were in the top 5 currently relevant allergens for HD, FD, and HFD. Other top allergens, as well as allergen sources, differed between HD, FD, and HFD. LIMITATIONS: No data on HD or FD morphology or distribution. CONCLUSION: HD, FD, and HFD have several differences with respect to patient characteristics, etiologies, and clinically relevant allergens.

Patch testing with glucosides: The North American Contact Dermatitis Group experience, 2009-2018.

BACKGROUND: Alkyl glucosides are nonionic surfactants that are increasingly used in personal care products. OBJECTIVE: To characterize positive patch test reactions to decyl glucoside (5% petrolatum, tested 2009-2018) and lauryl glucoside (3% petrolatum, tested 2017-2018). METHODS: Retrospective analysis of patients tested by the North American Contact Dermatitis Group. RESULTS: Of 24,097 patients patch tested to decyl and/or lauryl glucoside, 470 (2.0%) had positive reactions. Compared with glucoside-negative patients, glucoside-positive patients had higher odds of occupational skin disease (13.4% vs 10.1%; P = .0207), history of hay fever (38.5% vs 31.6%; P = .0014), atopic dermatitis (39.0% vs 28.6%; P < .0001), and/or asthma (21.8% vs 16.5%; P = .0023). Most glucoside reactions (83.9%) were currently relevant. The most common source was personal care products (63.0%), especially hair products (16.5%) and skin cleansers (15.2%). Of 4933 patients tested to decyl and lauryl glucoside, 134 (2.7%) were positive to 1 or both; 43.4% (43 of 99) of decyl-positive patients were also positive to lauryl glucoside and 55.1% (43/78) of lauryl glucoside patients were also positive to decyl glucoside. LIMITATIONS: The cohort predominantly reflects a referral population, and follow-up after testing was not captured. CONCLUSION: Glucoside positivity occurred in 2.0% of the tested patients. Reactions were often clinically relevant and linked to personal care products. Cross-reactivity was >40%.

Occupational contact dermatitis: Retrospective analysis of North American Contact Dermatitis Group Data, 2001 to 2016.

BACKGROUND: Patch testing is an important diagnostic tool for suspected allergic contact dermatitis (ACD) in occupational settings. OBJECTIVE: Provide an overview of occupational skin disease (OSD) and an analysis of occupational ACD in North American patients undergoing patch testing between 2001and 2016. METHODS: Patients with OSD were analyzed for frequency of allergic reactions to a screening series of allergens, occupational relevance, location of skin disease, and exposure sources. Demographic, occupation, and industry information were recorded. RESULTS: Of 38,614 patients evaluated, 4471 (11.6%) had OSD, of whom 3150 (70.5%) had ACD. The most common occupationally related allergens included rubber accelerators, preservatives, and bisphenol A epoxy resin. Hands (75.8%), arms (30.0%), and face (15.9%) were common sites of dermatitis. The occupations most affected were service workers and machine operators. LIMITATIONS: Our cohort may not reflect the general working population. CONCLUSION: This study identified common occupational allergens, exposure sources, and occupations/industries at risk. This information may help the clinician evaluate and manage patients with occupational contact dermatitis.

Patch testing with ammonium persulfate: The North American Contact Dermatitis Group Experience, 2015-2018.

BACKGROUND: Ammonium persulfate (APS), an oxidizing agent used in hair products, manufacturing, and pool/spa water, can cause skin reactions, including allergic contact dermatitis. OBJECTIVE: To characterize positive patch test reactions to APS (2.5% petrolatum). METHODS: Retrospective analysis of patients tested to the North American Contact Dermatitis Group screening series from 2015 to 2018. RESULTS: Of 10,526 patients, 193 (1.8%) had positive patch test reactions to APS. Compared with APS-negative patients, APS-positive patients were significantly more likely to be male (43.2% vs 28.0%; P < .0001); have primary hand dermatitis (30.2% vs 22.0%; P = .0064), scattered generalized dermatitis (25.5% vs 17.9%; P = .0064), or trunk dermatitis (8.9% vs 4.9%; P = .0123); and have dermatitis that is occupationally related (22.2% vs 10.9%; P < .0001). More than half of the APS-positive reactions were currently relevant (57.0%); 19 (9.8%) were related to occupation, especially hairdressers (68.4%). Swimming pools/spas (23.3%) and hair care products (19.2%) were the most common sources of APS. LIMITATIONS: Immediate reactions and follow-up testing were not captured. CONCLUSION: The proportion of patients positive to APS was 1.8%. APS positivity was significantly associated with male sex and hand dermatitis. Swimming pool/spa chemicals were important sources of APS exposure.

Age-related differences in patch testing results among children: Analysis of North American Contact Dermatitis Group Data, 2001-2018.

BACKGROUND: An updated understanding of allergic contact dermatitis is needed, particularly in children. OBJECTIVES: To compare positive and clinically relevant reactions in children versus adults referred for patch testing. METHODS: Retrospective analysis of 1871 children and 41,699 adults from the North American Contact Dermatitis Group (NACDG) from 2001-2018. RESULTS: Both final diagnosis of allergic contact dermatitis (55.2% versus 57.3%; chi square, P = .0716) and prevalence of ≥ 1 currently relevant reaction to a NACDG screening allergen (49.2% vs 52.2%; P = .1178) were similar between children and adults. Currently in children, the most common relevant allergens were nickel sulfate (17.3%), hydroperoxides of linalool (7.8%), methylisothiazolinone (7.7%), cobalt chloride (7.0%), and fragrance mix I (4.9%). Approximately a fifth of children had a positive reaction to a non-NACDG allergen. CONCLUSION: Over half of children referred for patch testing were diagnosed with allergic contact dermatitis. The most common relevant allergens in children were nickel sulfate, cobalt chloride, and hydroperoxides of linalool. Twenty percent of children had at least 1 positive reaction to allergens/substances not on the NACDG screening series, underscoring the need for comprehensive testing.

Medical adhesive allergens: Retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2018.

BACKGROUND: Identification of allergens causing medical adhesive contact allergy is difficult. OBJECTIVE: To characterize the demographics, clinical characteristics, patch test results, and occupational data for North American Contact Dermatitis Group patients with medical adhesive contact allergy. METHODS: A retrospective study of 43,722 North American Contact Dermatitis Group patients patch tested from 2001 to 2018 with medical adhesive (tapes/bandaids/adhesive aids/suture glue) sources, positive patch test results, and final primary diagnoses of allergic contact dermatitis. RESULTS: In total, 313 (0.7%) patients met the inclusion criteria. Compared with other patients with final primary diagnoses of allergic contact dermatitis, patients with a medical adhesive allergy were less likely to be male (odds ratio, 0.58; 95% CI, 0.45-0.77) and/or aged >40 years (odds ratio, 0.76; 95% CI, 0.60-0.96). The most common North American Contact Dermatitis Group screening series allergens were colophony (80.7%), balsam of Peru (3.9%), 2-hydroxyethyl methacrylate (2.7%), and carba mix (2.7%). One-fourth of the patients (79/313, 25.2%) had positive patch test reactions to supplemental allergens/materials, and 54 (17.3%) of the 313 patients only had reactions to supplemental allergens/materials. LIMITATIONS: Results of comprehensive patch testing may be prone to referral population selection bias and may not be representative of the general dermatology population. CONCLUSION: Colophony was the most common allergen. Supplemental allergens and materials should be tested in the evaluation of a suspected medical adhesive contact allergy.

Noninvasive diagnostic techniques in the preoperative setting of Mohs micrographic surgery: A review of the literature.

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.

Flow-through versus static in vitro percutaneous penetration at 50 years: Possible relevance for bioequivalence.

OBJECTIVE: Compare the relevance of flow-through versus static diffusion cells data as relates to bioequivalence. METHODS: Search was conducted on PubMed and Google Scholar. Keywords utilized: static cells, flow-through cells, percutaneous permeation, percutaneous absorption, dermal absorption, and types of permeation. RESULTS: Fifteen articles were identified with no consistent significant differences between flow-through and static diffusion cells identified; any differences could exist for two main reasons. (1) Sampling time differences and (2) physical chemistry (lipophilic vs hydrophilic) of the penetrant examined. CONCLUSION: Even though there was no consistent significant difference observed, labs have generally adapted to the method they regularly use, which is usually stated in their respective articles. Well-designed multicentered prospective comparative experiments should clarify potential advantages and disadvantages for each. For flow-through systems, the flow rate that most approximates to comparable in vivo data for animals and humans may be preferable.

How many skin barriers haveth we: Percutaneous egression of ions?

INTRODUCTION: Skin provides critical barrier properties that enable terrestrial life. Myriad research has focused on the "water barrier" to transepidermal water loss (TEWL) despite there being a multitude of skin barrier properties. We asked what other barrier properties may have been overlooked and compiled data demonstrating the "electrolyte barrier" to be of potential clinical relevance. METHODS: A literature search was conducted through PubMed, Embase, Google Scholar, and Web of Science databases for the following keywords: "transepidermal" or "epidermal" or "cutaneous" or "skin" or "percutaneous" and "ion" or "sodium" or "chloride" or "potassium" or "electrolyte" and "flux" or "egression." Textbooks at the University of California, San Francisco were also hand reviewed. Experimental studies quantifying in vivo or ex vivo percutaneous egression of ions in response to human skin barrier perturbation were included. RESULTS: Experimental damage to skin, mostly by tape-stripping, frequently induced increased ion flux rates through the epidermis, in addition to increases in TEWL values. Interestingly, barrier perturbation did not always result in a concomitant rise in TEWL and transepidermal ion flux rates, such as in delipidization, indicating a distinction between the two barriers. CONCLUSION: Quantifying the percutaneous egression of ions in response to physical or chemical alterations may offer additional data that are not to be captured with TEWL studies exclusively. Continued efforts should be made to: (1) advance this technique as a method of assessing skin status and (2) enhance our understanding of other barriers and mechanisms.

Role of skin autofluorescence in managing renal and cardiac diseases in outpatient dermatology.

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.

Dose response effect of chemical surface concentration on percutaneous penetration in human: In vivo + in vitro.

The concentration of a formulation, defined as the mass of applied chemical per unit of skin surface area, is a key variable of skin absorption. Often only one concentration is available in the literature, hence a general evidence-based theory could allow prediction of how altering the concentration would produce a linear, increased, or decreased relative permeation. Here, we group topical chemicals into groups of how they permeate the skin when we increase or decrease their concentrations per unit area and discuss why we would like to predict their permeability in ranges of studied concentrations. PURPOSE: Our research question is: How, if at all, do changes in surface chemical concentration affect percutaneous penetration/absorption in man? Specifically, as the drug concentration is relatively increased, is the rate or extent of absorption proportionally affected? And if so, how? METHODS: We searched PubMed, Google Scholar, the United States Food and Drug Administration, Scientific Committee on Consumer Safety, and the European Food Safety Authority for approved transdermal delivery systems from January 1965 to October 2020. Search terms included combinations of the following words: topical + [absorption/penetration] + cm + [human/man]. RESULTS: Of the nineteen chemicals identified, five (testosterone, hydrocortisone, benzoic acid, fluazifop-butyl and lindane) showed decreased percent absorbed with increased dose, one (2-butoxyethanol) showed decreased flux with increased concentration, and thirteen (Basic Brown 17, benzene in gasoline, benzophenone-3, benzoyl peroxide, boric acid, caffeine, climbazole, diclofenac, ethanolamines, ibuprofen, N-octylamine, 2-phenoxyethanol, 2-pyrrolidone) showed increased flux with increasing concentrations. CONCLUSION: Dermal absorption depends on the interaction between the characteristics of the substance, the vehicle, and the skin. Without experiments investigating these characteristics, we cannot accurately predict the percent absorbed or flux of a formulation without in vitro or in vivo data. More experimental data, especially in vivo, is mandated before a highly efficient prediction model will be reached for validation.

Efficacy of water skin decontamination in vivo in humans: A systematic review.

With the constant possibility of occupational exposures, chemical warfare, and targeted attacks, increased attention has been given to determining effective and timely dermal decontamination strategies. This systematic review summarises experimental studies reporting decontamination with water-based solutions of dermal chemical contaminants with in vivo human data. Embase, MEDLINE, PubMed, Web of Science, and Google Scholar databases were comprehensively searched using search terms ("cutaneous" or "skin" or "dermal" or "percutaneous") and ("decontamination" or "decontaminant" or "skin decontamination") to include 10 studies, representing 18 chemical contaminants, 199 participants, and 351 decontamination outcomes. Three studies included data from decontamination with water (10.8%, n = 38/351 decontamination outcomes), seven with soap and water (68.4%, n = 240/351 decontamination outcomes), and two with 10% isopropanol distilled water (20.8%, n = 73/351 decontamination outcomes). Results of dermal decontamination using water showed complete decontamination (CD) outcomes in 52.6% (n = 20/38) and partial decontamination (PD) in 47.4% (n = 18/38); using soap and water showed PD outcomes in 92.9% (n = 223/240) and minimal to no effect in 7.1% (n = 17/240); and using 10% isopropanol distilled water achieved PD outcomes in 100.0% (n = 73/73). Available data show that decontamination with water, soap and water, and 10% isopropanol distilled water is incomplete. Much remains to be learned about decontamination of the large variety of chemical contaminants including a range of molecular weights, lipid and water solubilities, melting points, volatility, and hydrogen bonds, as well as clinically relevant anatomic sites. A major void exists in data confirming or denying the completeness of decontamination by measuring absorption and excretion. The development of effective decontamination solutions is of high priority.