Alcohol-based Formulations Research Articles

Chlorhexidine is not an essential component in alcohol-based surgical hand preparation: a comparative study of two handrubs based on a modified EN 12791 test protocol

BackgroundSurgical hand preparation is an essential part of modern surgery. Both alcohol-based and antiseptic detergent-based hand preparation are recommended practices, with a trend towards use of alcohol based handrubs. However, discussion has arisen whether chlorhexidine is a required ingredient in highly efficacious alcohol-based formulations, in view of providing sustained antimicrobial efficacy.MethodsOne alcohol-only formulation (product A), containing ethanol and n-propanol, and one formulation containing a chlorhexidine-ethanol combination (product B) were directly compared with each other using a modified test protocol based on European standard EN 12791 (2016) with 25 volunteers. The alcohol-only formulation (product A) was applied for only 90 s, the chlorhexidine-alcohol formulation (product B) for 180 s. Microbial log reduction factors were determined and statistically compared immediately after application and at 6 h under surgical gloves.ResultsThe alcohol-only formulation (product A) achieved mean log reduction factors of 1.96 ± 1.06 immediately after application and 1.67 ± 0.71 after 6 h. The chlorhexidine-alcohol combination (product B) achieved mean log reduction factors of 1.42 ± 0.79 and 1.24 ± 0.90 immediately and after 6 h, respectively. The values for product A were significantly greater than those for product B at both measured time points (p ≤ 0.025 immediately after application and p ≤ 0.01 after 6 h).ConclusionsAn optimized alcohol-only formulation tested according to a modified EN 12791 protocol in 25 healthy volunteers outperformed a chlorhexidine-alcohol formulation both immediately after application and at 6 h under surgical gloves, despite a much shorter application time. Thus, optimized alcohol-only formulations do not require chlorhexidine to achieve potent immediate and sustained efficacy. In conclusion, chlorhexidine is not an essential component for alcohol-based surgical hand preparation.

Efinaconazole Topical Solution, 10%: Formulation Development Program of a New Topical Treatment of Toenail Onychomycosis

Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate.

Alcohol preparation compared to traditional surgical hand antisepsis: acceptance by surgical team at a private hospital in Brazil

Traditional surgical hand scrubbing (TSHS) has been replaced by alcohol-based formulation (ABF) in many countries due to antimicrobial efficacy, easy application, lower skin damage, time saver and no recontamination risk by rinsing hands with water [1]. In Brazil, chlorhexidine (CHG) and povidone-iodine (PVPI) are used for TSHS.

Hygienic safety of alcohol-based hand disinfectants and skin antiseptics.

Purpose: The aim of this study was to evaluate the overall risk of hand disinfectants and skin antiseptics to become contaminated with bacterial spores throughout the production process and the subsequent in-use period, hence posing a public health risk. Methods: Microbiological assessment of primary packaging material was carried out and long-term survival of bacterial spores in alcohol was assessed using sporulated B. subtilis ATCC 6633 as a standard. In-use contamination of alcohol-based formulations was tested by repeated use over 12 months under practical conditions and microbiological and physico-chemical data were determined.Results: Among 625 containers analyzed, 542 did not yield any microbial growth. Median colony count for aerobic spore-forming bacteria was 0.2 cfu/10 ml container content. No anaerobic spore-forming bacteria were detected. Additionally, long-term survival of bacterial spores in aliphatic C2–C3 alcohols revealed 1-propanol to reduce the number of spores most effectively, with 2-propanol and ethanol having a somewhat less pronounced impact. In-use tests did not detect any microbial contamination or change in the physicochemical properties of the tested products over 12 months. Conclusions: Our data reveals that state-of-the-art production processes of alcohol-based hand rubs and antiseptics can be regarded safe. Primary packaging material and use were not found to pose a significant contamination risk as far as bacterial spores are concerned. Based on the data from this study, a microbial limit of <1 cfu/10 ml can be suggested as a quality-control threshold for finished goods to ensure high quality and safe products.

Glycerol significantly decreases the three hour efficacy of alcohol-based surgical hand rubs

Glycerol in alcohol-based hand rubs has positive effects on skin condition and user acceptability, but, to the authors' knowledge, its effect on the bactericidal effect of alcohol-based pre-operative hand rubs has not been reported. To investigate the impact of glycerol on the reduction of resident hand flora by ethanol 80% (w/w), isopropanol 75% (w/w) and n-propanol 60% (V/V). In three series of in-vivo laboratory tests on volunteers hands, the efficacy of each of three alcohol-based formulations was tested concurrently with and without added glycerol 1.45% (V/V) according to European Norm EN 12791 for testing pre-operative hand rubs. Formulations were allotted at random to 24 volunteers to rub on to their hands for 3min. Viable counts from fingertip samples were compared with the respective pretreatment counts immediately after treatment and 3h later. The 3-h bactericidal effects of the three pure alcoholic formulations were significantly greater than those of formulations containing glycerol (P<0.01). With ethanol, this was also true for the immediate effect. Glycerol 1.45% (V/V) inhibits the bactericidal efficacy of alcohol-based surgical hand rubs, especially sustained efficacy.

Insects Which Occur in Food Factories and Its Control Methods

At food factories or pharmaceutical factories, serious damages may be given to their company brand image by only one contamination. Insects could be one of the foreign substances with a high possibility of contamination to products in the process of manufacture. Insects frequently found in food factories are roughly divided into two types. One is insects which invade factories by flying or crawling, and the other is that can occur inside factories repeatedly. I introduce insects which can occur for generations in the manufacturing area of food factories and its effective control methods. Insects which occur in manufacturing area feed on mold, dust, food waste, scum, sludge, stored food such as grain as food sources. Moreover, insects which prey on such insects may occur and settle in factories. To rid the arias of the food sources is one of the best solutions to solve these insect problems. In addition, alcohol-based formulations, hypochlorous acid water, and other chemical agents should be used together depending on the situation.

Hand hygiene compliance in the critical care setting: A comparative study of 2 different alcohol handrub formulations

Hand hygiene (HH) compliance can be affected by the accessibility of products (alcohol-based products or chlorhexidine) and by the formulations of these products. There are few published studies comparing different alcohol-based hand disinfection formulations. This study was conducted in a 41-bed medical-surgical intensive care unit at a private tertiary care hospital. Over a 16-week period, we assessed HH compliance by direct observation of practice using iPods and measurement of the amount of product used [alcohol and chlorhexidine] in two 4-room pods in which an alcohol gel product was used compared with two other 4-room pods in which an alcohol-based foam formulation was used. A total of 3,895 opportunities for HH were observed, and the overall rate of HH compliance was 36.9%. No statistically significant differences were found in overall HH compliance or alcohol-based HH compliance between the alcohol foam unit and the alcohol gel unit. However, there was a statistically significant difference in chlorhexidine HH compliance between the alcohol foam unit and the alcohol gel unit (7.0% [130 of 1,853] vs 3.8% [77 of 2,042]; P < .01). Alcohol handrub use was greater than chlorhexidine use, but HH compliance was low in both units independent of the alcohol formulation available. The similarity of use of both alcohol formulations suggests that health care workers tend to use whatever product is readily available.

Physicochemical Characterization of Nanotemplate Engineered Solid Lipid Nanoparticles

As the physicochemical characteristics of solid lipid nanoparticles (SLNs) play a critical role in their success, it is important to understand how the materials and process used in their preparation affect these properties. In this study, two stearyl alcohol-based formulations were prepared using nanotemplate engineering technology and characterized. Both formulations were of a small particle size (<100 nm), ellipsoidal shape, and low polydispersity. (1)H NMR spectroscopy confirmed that the SLNs have the expected solid core structure and PEGylated surface. Analysis of the bulk materials indicated that a number of complex interactions are present among the SLN components, including a eutectic between stearyl alcohol and Brij 78. The decreased crystallinity resulting from these interactions may allow for enhanced drug loading. Physiological stability was identified and confirmed as a potential problem due to the low melting point of the eutectic. However, it is expected that with appropriate formulation modifications nanotemplate engineered SLNs will possess the properties necessary for a successful drug delivery system.

Assessment of the dermal and ocular irritation potential of alcohol hand sanitizers containing aloe vera with in vitro and in vivo methods

Alcohol-based hand sanitizers have been proven effective in reducing the spread of microbial infections. However, frequent use of alcohol-based formulations of hand sanitizers can cause adverse skin effects, such as allergic and irritant contact dermatitis. Thus, we evaluated the irritant potency of alcoholbased hand sanitizers containing aloe vera and clove extract with four irritation studies and compared in vivo and in vitro results. The Draize rabbit eye and skin irritancy tests were conducted to evaluate the in vivo ocular and dermal irritation potential. For in vitro evaluation of skin irritation, tissue damage was assessed with the MTT assay and by examining the release of interleukin-1α (IL-1α) using engineered epidermal equivalents (KeraSkin™). A 3T3-neutral red uptake (NRU) assay was performed as a potential alternative to the Draize eye irritation test. Sanitizers containing aloe vera and clove extract were non-irritating to skin, and the results were comparable with both the in vivo and in vitro MTT viability assay. However, an increase in IL-1α release was observed. The results of the in vivo eye irritation toxicity studies in rabbits demonstrated reversible conjunctival redness and edema, whereas the test article was non-irritating in the in vitro 3T3-NRU study. These data indicate that the eye is more sensitive to alcohol-based hand sanitizerinduced damage than the skin. Furthermore, in vitro tests are useful for screening purposes, but not for the elimination of in vivo testing.

Virucidal activity of 2 alcohol-based formulations proposed as hand rubs by the World Health Organization

The virucidal activity of 2 hand rubs proposed by the World Health Organization was studied in a quantitative suspension test for chemical disinfectants and antiseptics in human medicine (EN 14476). These formulations are recommended if no hand rubs with declared microbiological activity are available in health care settings. Formulation I, based on ethanol, inactivated bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV), adenovirus, and murine norovirus as a surrogate for human norovirus. Formulation II, based on isopropyl alcohol, was active only against adenovirus and enveloped viruses, such as BVDV and HCV. Both formulations failed to inactivate poliovirus by 4 log(10) steps within 300 seconds.

Repellency of Hydrogenated Catmint Oil Formulations to Black Flies and Mosquitoes in the Field

The essential oil of catmint, Nepeta cataria L., was hydrogenated to yield an oil enriched in dihydronepetalactone (DHN) diastereomers, termed. This material was used for the preparation of liquid alcohol-based and lotion formulations. The efficacy of these formulations as repellents was tested after application to human test subjects at two locations in the United States: Maine and Florida. In Maine, data on repellency of the hydrogenated catmint oil formulations toward black flies (Simulium decorum Walker) and mosquitoes (primarily Aedes intrudens Dyar) were obtained. In these tests, protection from black flies was conferred for 6 h or more with all formulations, and both liquid and lotion formulations at 15 wt% active ingredient gave complete protection for 7.5 h. All formulations conferred protection from mosquitoes for >4 h, with the best (15 wt% lotion) giving >8 h of complete protection. In Florida, data on repellency toward a mixed population of mosquitoes indicated that all formulations conferred protection for >4 h, with the 15 wt% lotion giving >6 h complete protection from bites.

Hand Hygiene: It's All About When and How

From the Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, and World Health Organization First Global Patient Safety Challenge, Word Health Organization Headquarters, Geneva, Switzerland. Received July 25, 2008; accepted July 31, 2008; electronically published August 28, 2008. Infect Control Hosp Epidemiol 2008; 29:957-959 2008 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2008/2910-0010$15.00.DOI: 10.1086/592218 Hand hygiene is the primary measure for infection prevention. When appropriately performed, it reduces the crosstransmission of microbial pathogens and the burden of infectious diseases, both in the community and in the healthcare setting. The major challenge for hand hygiene is compliance, which is usually much less than 50% in most hospitals. Barriers to compliance have been identified at individual, group, and institutional levels. In healthcare settings where epidemiological studies assessed and quantified the role played by such barriers, promotion strategies have been developed and applied successfully—resulting in improved compliance and decreased rates of cross-transmission and infection. To succeed, however, strategies must be multimodal and include at least 5 components: staff education, monitoring of practices and performance feedback, reminders in the workplace, adoption of an institutional safety climate, and, last but not least, a system change—the preferential recourse to the use of alcohol-based hand rub as the new standard for patient care. Hand hygiene with alcohol-based formulations is preferred to hand washing with soap and water in most instances, because it is fast-acting, more efficacious, causes less damage to the skin, and has the major advantage of being immediately accessible at the point of patient care, thus bypassing the time constraint—one of the most critical barriers to hand hygiene in a healthcare setting. Although the majority of studies on hand-hygiene compliance have focused on the time and frequency of action (ie, when to clean hands), only a few have addressed the topic of how to clean hands. In this issue of the journal, Laustsen et al. report on their study that monitored how hand rubbing with alcohol gel was performed at the bedside and corroborated correctness of practice with antimicrobial efficacy. The findings are staggering. Only 55% of staff performed the action correctly, despite being closely monitored by an observer who took imprints of their fingertips before and after hand rubbing with alcohol gel during clinical care procedures. Incorrect practice was associated with a 35% decrease in efficacy, regardless of whether imprints for culture were obtained before the clinical procedure (when hand hygiene was performed to protect the patient) or after (when hand hygiene was performed to protect the healthcare worker or the next patient that he or she would be in contact with). This study adds to previous findings regarding both hand rubbing with alcohol gel and hand washing with soap in suggesting that not only the timing and frequency of hand hygiene must improve, but also its basic qualitative performance. Tools and innovative strategies exist; they just have to be taught and applied. It is obvious that the clinical significance of the findings of Laustsen et al. remains unknown as yet. However, let us stand back and reconcile it with current evidence-based knowledge. Infection control professionals would ideally ask healthcare workers to be 100% compliant with hand-hygiene

Chlorhexidine-Based Antiseptic Solution vs Alcohol-Based Povidone-Iodine for Central Venous Catheter Care

Although chlorhexidine-based solutions and alcohol-based povidone-iodine have been shown to be more efficient than aqueous povidone-iodine for skin disinfection at catheter insertion sites, their abilities to reduce catheter-related infection have never been compared. Consecutively scheduled central venous catheters inserted into jugular or subclavian veins were randomly assigned to be disinfected with 5% povidone-iodine in 70% ethanol or with a combination of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzylic alcohol. Solutions were used for skin disinfection before catheter insertion (2 consecutive 30-second applications separated by a period sufficiently long to allow for dryness) and then as single applications during subsequent dressing changes (every 72 hours, or earlier if soiled or wet). Of 538 catheters randomized, 481 (89.4%) produced evaluable culture results. Compared with povidone-iodine, the chlorhexidine-based solution was associated with a 50% decrease in the incidence of catheter colonization (11.6% vs 22.2% [P = .002]; incidence density, 9.7 vs 18.3 per 1000 catheter-days) and with a trend toward lower rates of catheter-related bloodstream infection (1.7% vs 4.2% [P = .09]; incidence density, 1.4 vs 3.4 per 1000 catheter-days). Independent risk factors for catheter colonization were catheter insertion into the jugular vein (adjusted relative risk, 2.01; 95% confidence interval, 1.24-3.24) and use of povidone-iodine (adjusted relative risk, 1.87; 95% confidence interval, 1.18-2.96). Chlorhexidine-based solutions should be considered as a replacement for povidone-iodine (including alcohol-based) formulations in efforts to prevent catheter-related infection.

Patient preferences for facial sunscreens: A split-face, randomized, blinded trial

Sunscreen use is a widely accepted method of primary prevention against skin cancer, sunburn, and photoaging. However, many people do not routinely apply sunscreen because they find application objectionable. To determine which types of sunscreen subjects are willing to use on more than one occasion. A split-face, randomized, blinded trial of commercially available sunscreens was performed among 139 community members in Rochester, Minnesota. Subjects were significantly more likely to indicate that they would use alcohol-based spray sunscreen again than two of the seven sunscreens assessed (P < .05). This sunscreen was endorsed as being less greasy, less likely to leave a film, and less likely to leave them feeling hot and sweaty than at least two of the other sunscreens. Only a representative selection of commonly available sunscreens was tested. An alcohol-based spray formulation of sunscreen was rated more favorable. Recommendations to use alcohol-based spray sunscreens may increase patient compliance.

Virucidal activity of a new hand disinfectant with reduced ethanol content: comparison with other alcohol-based formulations

SummaryA new formula with reduced ethanol content (55%) in combination with 10% propan-1-ol, 5.9% propan-1.2-diol, 5.7% butan-1.3-diol and 0.7% phosphoric acid exhibited a broad spectrum of virucidal activity. In quantitative suspension tests, with and without protein load, this formulation reduced the infectivity titre of seven enveloped (influenza A and B, herpes simplex 1 and 2, bovine corona, respiratory syncytial, vaccinia, hepatitis B, bovine viral diarrhoea) and four non-enveloped (hepatitis A, polio, rota, feline calici) viruses >103-fold within 30 s. In comparative testing, only 95% ethanol showed similar levels of activity.In fingerpad tests, the formulation produced a log10 reduction factor of the titre of poliovirus type 1 (Sabin) of 3.04 in 30 s compared with 1.32 by 60% propan-2-ol. Testing against feline calicivirus produced a log10 reduction factor of 2.38 by the test formulation; in contrast, the log10 reduction factors with 70% ethanol and 70% propan-1-ol were 0.68 and 0.70, respectively.

Hygienische und dermatologische Aspekte der Händedesinfektion und der prophylaktischen Hautantiseptik

Hygienic hand disinfection must be carried out after all patient-care activities associated with contamination risks, as well as when moving from contaminated to clean body sites, after contact with environmental surfaces in the immediate vicinity of patients, after glove removal and before aseptic procedures. Preparatory handwashing (for about 10 seconds) to mechanically remove soil and bacterial spores should be performed at least 10 minutes before surgical hand disinfection. This allows time for the normalization of increased skin hydration, a prerequisite for effective hand disinfection. Depending on the manufacturer's instructions, application times of 1.5, 3 or 5 minutes can be observed. The regular use of skin care and skin protection products can help to prevent toxic skin irritation. For skin antisepsis the recommended exposure times are > or =15 seconds before subcutaneous injections, > or =1 minute before puncture of joints and body cavities as well as preoperatively, and > or =10 minutes on skin areas rich in sebaceous glands. For all 3 indications, alcohol-based formulations are the agents of choice.

Zinc pyrithione in alcohol-based products for skin antisepsis: Persistence of antimicrobial effects

Alcohol-based products for skin antisepsis have a long history of safety and efficacy in the United States and abroad. However, alcohol alone lacks the required antimicrobial persistence to provide for the sustained periods of skin antisepsis desired in the clinical environment. Therefore, alcohol-based products must have a preservative agent such as iodine/iodophor compounds, chlorhexidine gluconate, or zinc pyrithione, to extend its antimicrobial effects. Iodine, iodophors, and chlorhexidine gluconate are well-characterized antimicrobials and preservatives. The thrust of our effort was to examine the characteristics of the lesser-known zinc pyrithione and to evaluate its utility as a preservative in the formulation of alcohol-based products for skin antisepsis. This work includes a literature review of current zinc pyrithione applications in drugs and cosmetics, a safety and toxicity evaluation, consideration of the proposed mechanisms of antimicrobial action, in vitro and in vivo efficacy data, and a discussion of the mechanisms that confer the desired antimicrobial persistence. In addition, alcohol-based, zinc pyrithione-preserved, commercially available products of skin antisepsis are compared with other commercially available antimicrobials used for skin antisepsis and with additional alcohol-based products with different preservatives. The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.

Antimicrobial Persistence and Residual Effect in Healthcare Personnel Handwashes

BACKGROUND: Alcohol-based hand sanitizers can reduce nosocomial infections by >30.0%. The Food and Drug Administration (FDA) via the Tentative Final Monograph assesses efficacy immediately post wash. Antimicrobial persistence and residual effect are not evaluated. Recently a novel water-optional, alcohol-based formulation preserved with zinc pyrithione has been developed that provides antimicrobial persistence and residual activity, while surpassing the FDA criteria as a healthcare personnel handwash in both the waterless and water-aided modes. METHODS: This formulation was compared to common handwashes containing various antimicrobials (0.5% triclosan, 61.0% ethanol, 2.0% chlorhexidine gluconate [CHG], and 4.0% CHG) in waterless and/or water-aided modes to assess immediacy of kill, persistence, and residual effects in a 5-day study employing >60 subjects. Following collection of baseline data, the participants were instructed to wash with each product four times within 1 hour per label instructions and then glove. Representative samples were taken by the glove juice method at selected post-wash intervals that included immediate, 4-hour (except 4.0% CHG), and 8-hour. Post-wash samples were compared to baseline and log10 reductions were calculated. RESULTS: When tested waterless, the water-optional product consistently produced log10 reductions of nearly 3.5 or greater at every point over the entire study period, demonstrating vastly superior efficacy over the CHG and other alcohol-based products. In the water-aided configuration, similar results were obtained, as log10 reductions of 2.5 were observed, thus demonstrating vastly superior efficacy over triclosan. CONCLUSIONS: The new formulation exceeds FDA criteria for classification as a healthcare personnel handwash and demonstrates exceptional persistence and residual effects.

In vitro dermal disposition of abamectin (avermectin B 1) in livestock

Many avermectins are approved for topical application in domestic animals. However, extralabel use may result in significant dermal absorption and consequently the potential for adverse effects or violative residues. The primary aim of this study was to assess dermal disposition of abamectin in vitro in bovine, caprine, ovine, and porcine skin dosed in 100% isopropanol, commercial alcohol-based (Ivomec), or oil-based (Eprinex) formulations. Skin sections were perfused in a flow-through diffusion cell system for 8 h, and the disposition of radiolabel abamectin was determined from perfusate and skin samples. Abamectin absorption ranged from 0.09% to 0.20% dose and there were no significant differences between formulations in each species. Isopropanol significantly increased skin deposition in all species when compared to the oil formulation. Absorption was significantly greater in bovine skin than in porcine skin for the isopropanol-containing formulations, but there were no significant species differences for the oil formulation. While significant levels (11.69–50.23% dose) remained on the skin surface, the highest levels deposited in viable skin were observed in caprine skin (28.09% dose) and the lowest levels were in porcine skin (1.50% dose) which could lead to systemic absorption. In summary, these 8-h experiments demonstrated that the alcohol-based formulations compared to oil-based formulations enhanced abamectin absorption and skin deposition in several animal species, and this effect is more likely to be observed in ruminant species than in porcine species.

Hand hygiene: improved standards and practice for hospital care.

To review the most recently published literature on hand hygiene practices in healthcare settings. Adherence with recommendations for hand hygiene remains low, but key factors of noncompliance have been identified and corrective actions proposed. Current guidelines recommend the use of alcohol-based handrub formulations as the new standard of care, thus requiring a system change in most hospitals. In addition, healthcare worker education and motivation are obviously important to modify hand hygiene behavior and must be part of multimodal strategies to enhance compliance in hospitals. Compliance improvement is associated with reduced infection rates and resistance spread. Handrub application according to recommended practices is an alternative to conventional surgical handscrubbing with antiseptic soap and water for surgical hand preparation. System change must be addressed in most hospitals where alcohol-based handrubbing has not become a standard of care. Strategies to improve hand hygiene compliance must be multimodal and include staff education and motivation, the use of performance indicators, and hospital management support. Successful campaigns will result in reduced infection rates, antimicrobial resistance spread, and enhance patient safety.