Hand Sanitizers: a Review on Formulation Aspects, Adverse Effects, and Regulations
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International Journal of Environmental Research and Public Health Review Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations 1, 1, 2 2 Jane Lee Jia Jing y, Thong Pei Yi y, Rajendran J. C. Bose , Jason R. McCarthy , Nagendran Tharmalingam 3 and Thiagarajan Madheswaran 4,* 1 School of Pharmacy, International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia; [email protected] (J.L.J.J.); [email protected] (T.P.Y.) 2 Masonic Medical Research Institute, 2150 Bleecker St, Utica, NY 13501, USA; [email protected] (R.J.C.B.); [email protected] (J.R.M.) 3 Infectious Diseases Division, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA; [email protected] 4 Department of Pharmaceutical Technology, International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia * Correspondence: [email protected]; Tel.: +60-3-2731-7075 These authors contributed equally to this work. y Received: 26 March 2020; Accepted: 8 May 2020; Published: 11 May 2020 Abstract: Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%–95% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus. Keywords: hand sanitizer; hand disinfectants; infection control 1. Introduction The emergence of the COVID-19 (Coronavirus Disease-2019) pandemic has risen to be a significant global public health concern and led to extensive use of hand disinfectants given its contagious nature. There was a total of 3.8 million reported cases affecting over 200 countries worldwide as of 7 May 2020 [1,2]. COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can persist and remain infectious on surfaces for up to 9 days [3,4]. The recent study reveals that transmission of SARS-CoV-2 is possible in the form of aerosol and fomite, and the virus can remain viable and infectious in aerosols for hours and on surfaces up to days, depending on the inoculum shed [5]. Hence, it is crucial to interrupt the transmission chain of the virus through contact isolation and strict infection control tools [6]. Following face masks, appropriate hand hygiene is of utmost importance as hands may be contaminated from direct contact with patients’ Int. J. Environ. Res. Public Health 2020, 17, 3326; doi:10.3390/ijerph17093326 www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2020, 17, 3326 2 of 17 Int. J. Environ. Res. Public Health 2020, 17, x FOR PEER REVIEW 2 of 19 contaminated from direct contact with patients’ respiratory droplets from coughs and sneezes or respiratory droplets from coughs and sneezes or indirect contact via surfaces, which may then facilitate indirect contact via surfaces, which may then facilitate the transmission and spreading of the disease the transmission and spreading of the disease [7–9]. The 2003 severe acute respiratory syndrome [7–9]. The 2003 severe acute respiratory syndrome (SARS) outbreak was caused by a novel human (SARS)coronavirus outbreak (CoV) was (SARS-CoV) caused by athat novel could human survive coronavirus on surfaces (CoV) for 24 (SARS-CoV) to 72 h [10]. that The could studies survive on onSARS-CoV surfaces for outbreak 24 to 72 settings h [10]. Theshowed studies that on providing SARS-CoV efficient outbreak handwashing settings showed facilities that reduced providing effitransmissioncient handwashing [11]. facilities reduced transmission [11]. GivenGiven the the dangers dangers imposed imposed by by this this disease, disease, the the Centre Centre for Diseasefor Disease Control Control and and Prevention Prevention (CDC), the(CDC), United the States United has States promoted has promoted and encouraged and encouraged hand hygiene hand hygiene through thro handwashingugh handwashing or use or of use hand sanitizerof hand [sanitizer12]. Hand [12]. disinfectants Hand disinfectants are commercially are commercially available available in variousin various types types and and forms forms suchsuch as anti-microbialas anti-microbial soaps, soaps, water-based water-based or alcohol-based or alcohol-ba handsed hand sanitizers, sanitizers, most most often often used inused hospital in hospital settings. Disettings.fferent types Different of delivery types of systems delivery are systems also formulated—for are also formulated—for instance, instance, rubs, foams, rubs, or foams, wipes or (Figure wipes 1). The(Figure World 1). Health The OrganisationWorld Health (WHO) Organisation recommends (WHO) alcohol-based recommends hand alcohol-based sanitizer (ABHS) hand insanitizer line with the(ABHS) proven in advantagesline with the ofproven their advantages rapid action of andtheir a rapid broad action spectrum and a broad of microbicidal spectrum of activity microbicidal offering protectionactivity offering against protection bacteria and against viruses. bacteria However, and viruses. the effectiveness However, againstthe effectiveness non-enveloped against viruses non- is stillenveloped debatable viruses and questionable is still debatable [7,13 and–18 questionable]. [7,13–18]. Figure 1. Various types of hand sanitizer dosage forms. Figure 1. Various types of hand sanitizer dosage forms. To date, most effective hand sanitizer products are alcohol-based formulations containing 62%–95% To date, most effective hand sanitizer products are alcohol-based formulations containing 62%– of alcohol as it is capable of denaturing the proteins of microbes and inactivating viruses [19,20]. 95% of alcohol as it is capable of denaturing the proteins of microbes and inactivating viruses [19,20]. ThereThere are are a fewa few challenges challenges and and concernsconcerns with regard to to this this formulation formulation in in terms terms of offire fire hazards hazards and and skinskin toxicity toxicity due due toto highhigh alcoholalcohol content content [21]. [21]. This This systemic systemic review review aims aims to investigate to investigate the range the range of ofavailable available hand hand sanitizers sanitizers and and their their effectiveness effectiveness against against the the human human coronavirus coronavirus as aswell well as asthe the formulationformulation aspects, aspects, adverseadverse eeffects,ffects, and recomme recommendationsndations to to improve improve the the formulation formulation of ofcurrent current handhand sanitizers. sanitizers. 2.2. Methods Methods ThisThis study study was was conducted conducted accordingaccording to the PRIS PRISMAMA recommendations recommendations [22]. [22 We]. We systematically systematically reviewedreviewed the the available available literature literature in in PubMed PubMed and and Google Google Scholar, Scholar, up up to to 2020. 2020. The The search search terms terms we we used areused hand are sanitizers hand sanitizers AND alcohol AND ANDalcohol treatment AND treatment AND handwashing AND handwash ANDing virucide AND virucide AND bactericide AND ANDbactericide (cure OR AND failure (cure OR OR mortality). failure OR mortality). A manual A search manual was search also performed.was also performed. We set noWe year set no limit, andyear English limit, and is the English only languageis the only welanguage limit. Thewe limit. study The selection study selection based on based effective on effective treatment treatment resulted inresulted a potential in a eradicationpotential eradication of pathogens. of pathogens. The data The extracted data extracted from from each each study study comprised comprised the the main characteristicsmain characteristics of the study,of the suchstudy, as such the firstas the author’s first author’s name, name, year, studyyear, study design, design, and country.and country. Out of manyOut reports,of many wereports, selected we selected articles basedarticles on based the hand on the disinfectant hand disinfectant agents andagents their and potential their potential outcome suitableoutcome for suitable the present for the viral present pandemic. viral pandemic. Data were Da extractedta were byextracted two authors by two based authors on thebased screening on the of the titles and abstracts obtained from the PubMed and Google Scholar database. The other authors have checked the materials to fulfil the criteria for the work. Int. J. Environ. Res. Public Health