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Hand and surface sanitizersA Practical Compounding Guide

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A. Practices Antiseptic handwashing Washing hands with soap and water, or other detergents containing an antiseptic agent.

Antiseptic handrubbing (or handrubbing) Applying an antiseptic handrub to reduce or inhibit the growth of microorganisms without the need for an exogenous source of water and requiring no rinsing or drying with towels or other devices.

B. Products Alcohol-based (hand) rub An alcohol-containing preparation (liquid, gel or foam) designed for application to the hands to inactivate microorganisms and/or temporarily suppress their growth. Such preparations may contain one or more types of alcohol, other active ingredients with excipients, and humectants.

Antiseptic agent An antimicrobial substance that inactivates microorganisms or inhibits their growth on living tissues. Examples include alcohols, chlorhexidine gluconate (CHG), chlorine derivatives, iodine, chloroxylenol (PCMX), quaternary ammonium compounds, and triclosan.

Waterless antiseptic agent An antiseptic agent (liquid, gel or foam) that does not require the use of exogenous water. After application, the individual rubs the hands together until the skin feels dry.

Definition of terms according to WHO Guidelines on hand hygiene in health care

* This guide was produced based on WHO Guidelines on Hand Hygiene in Health Care (ISBN 978 92 4 159790 6)

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A brief comparisonof the main antiseptics used

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Alcohol as the focus

The antimicrobial activity of alcohols results from their ability to denature proteins.

Alcohol solutions containing 60–80% alcohol are most effective, with higher concentrations being less potent. This paradox results from the fact that proteins are not denatured easily in the absence of water.

The alcohol content of solutions may be expressed as a percentage by weight (m/m), which is not affected by temperature or other variables, or as a percentage by volume (v/v), which may be affected by temperature, specific gravity and reac-tion concentration. For example, 70% alcohol by weight is equivalent to 76.8% by volume if prepared at 15 ºC, or 80.5% if prepared at 25 ºC. Alcohol concentrations in antiseptic handrubs are often expressed as a percentage by volume.

Most alcohol-based hand antiseptics contain either ethanol, isopropanol or n-propanol, or a combination of two of these products. Concentrations are given as either percentage of volume (= ml/100 ml, abbreviated % v/v), percentage of weight (= g/100 g, abbreviated % m/m), or percentage of weight/volume (= g/100 ml, abbreviated % m/v).

Important points• Alcohols are rapidly germicidal when applied to the

skin, but have no appreciable persistent (residual) ac-tivity – that is the reason why viscous formulations are recommended.

• Alcohols are not good cleansing agents and their use is not recommended when hands are dirty or visibly contaminated with proteinaceous materials.

• Because alcohols are volatile, containers should be designed so that evaporation is minimized and initial concentration is preserved.

Formulation tip!Frequent use of alcohol-based formulations for hand antisepsis tends to cause drying of the skin unless hu-mectants or other skin conditioning agents are added to the formulations.• For example, the drying effect of alcohol can be

reduced or eliminated by adding 1-3% glycerin, castor (ricinus) oil or otherskin conditioning agents.

• Moreover, in prospective trials, alcohol-based solu-tions or gels containing humectants caused signifi-cantly less skin irritation and dryness than the soaps or antimicrobial detergents tested.

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WHO-Recommended

Handrub Formulations

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I. Formulation I (glycerinated ethanol 80%, v/v)

A. METHOD OF PREPARATION

1. The alcohol is poured into the large bottle or tank up to the graduated mark.

2. H2O2 is added using the measuring cylinder.3. Glycerol is added using a measuring cylinder. As the glycerol

is very viscous and sticks to the walls of the measuring cylin-der, it can be rinsed with some sterile distilled or cold boiled water to be added and then emptied into the bottle/ tank.

4. The bottle/tank is then topped up to the corresponding mark of the volume (10-litre or 50-litre) to be prepared with the re-mainder of the distilled or cold, boiled water.

5. The lid or the screw cap is placed on the bottle/tank immedi-ately after mixing to prevent evaporation.

6. The solution is mixed by gently shaking the recipient where appropriate (small quantities), or by using a wooden, plastic or metallic paddle. Electric mixers should not be used.

7. After mixing, the solution is immediately divided into small-er containers (e.g. 1000, 500 or 100 mL plastic bottles). The bottles should be kept in quarantine for 72 hours. This allows time for any spores present in the alcohol or the bottles to be eliminated by H2O2.

C. PRESERVATION, PACKAGING AND STORAGE

• In a suitable container, made of amber glass or high-density opaque plastic, perfectly closed and protected from light, at room temperature.

E. STANDARD OPERATING PROCEDURE FOR QUALITY CONTROL

• Quality-control assessment can include alcohol concentration (alcoholmeter), H2O2 concentration (titrimetry: oxydo-reduction reac-tion by iodine in acidic conditions), density, viscosity, and physical appearance (color, uniformity). Moreover, the absence of microbial contamination (including spores) can be checked by filtration, according to the European Pharmacopeia specifications.

D. STABILITY

• A beyond-use date of 180 days can be used for this prepara-tion when stored in room temperature (USP <<795>>).

DOSAGE FORM: solution

FORMULA:To produce final concentrations of ethanol80% v/v,

glycerol 1.45% v/v, hydrogen peroxide (H2 O2) 0.125% v/v.

USE/TYPE:Human use. Non-Sterile

Preparation: solution.

Only pharmacopoeial quality reagents should be used (e.g. The International Pharmacopoeia) and not technical grade products

B. LABELING

The bottles should be labelled in accordance with national guidelines. Labels should include the following:• Name of institution• Date of production and batch number• Composition: ethanol or isopropanol, glycerol and hydrogen

peroxide (% v/v can also be indicated) and the following statements:• WHO-recommended handrub formulation• For external use only• Avoid contact with eyes• Keep out of reach of children• Use: apply a palmful of alcohol-based handrub and cover all

surfaces of the hands. Rub hands until dry. Flammable: keep away from flame and heat.

Ingredients Quantity

Ethanol 96% v/v 833.3 mL

H2O2 3% 41.7 mL

Glycerol 98% 14.5 mL

Distilled water, qs 1000 mL

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II. Formulation II (glycerinated isopropyl alcohol 75%, v/v)

A. METHOD OF PREPARATION

1. The alcohol is poured into the large bottle or tank up to the graduated mark.

2. H2O2 is added using the measuring cylinder.3. Glycerol is added using a measuring cylinder. As the glycerol

is very viscous and sticks to the walls of the measuring cylin-der, it can be rinsed with some sterile distilled or cold boiled water to be added and then emptied into the bottle/ tank.

4. The bottle/tank is then topped up to the corresponding mark of the volume (10-litre or 50-litre) to be prepared with the re-mainder of the distilled or cold, boiled water.

5. The lid or the screw cap is placed on the bottle/tank immedi-ately after mixing to prevent evaporation.

6. The solution is mixed by gently shaking the recipient where appropriate (small quantities), or by using a wooden, plastic or metallic paddle. Electric mixers should not be used.

7. After mixing, the solution is immediately divided into small-er containers (e.g. 1000, 500 or 100 mL plastic bottles). The bottles should be kept in quarantine for 72 hours. This allows time for any spores present in the alcohol or the bottles to be eliminated by H2O2.

C. PRESERVATION, PACKAGING AND STORAGE

• In a suitable container, made of amber glass or high-density opaque plastic, perfectly closed and protected from light, at room temperature.

E. STANDARD OPERATING PROCEDURE FOR QUALITY CONTROL

• Quality-control assessment can include alcohol titre, density, viscosity, and physical appearance (color, uniformity).

• Quality-control assessment can include alcohol concentration (alcoholmeter), H2O2 concentration (titrimetry: oxydo-reduction reac-tion by iodine in acidic conditions), density, viscosity, and physical appearance (color, uniformity). Moreover, the absence of microbial contamination (including spores) can be checked by filtration, according to the European Pharmacopeia specifications.

D. STABILITY

• A beyond-use date of 180 days can be used for this prepara-tion when stored in room temperature (USP <<795>>).

DOSAGE FORM: solution

FORMULA:To produce final concentrations of isopropyl alcohol 75%

v/v, glycerol 1.45% v/v, hydrogen peroxide 0.125% v/v

USE/TYPE:Human use. Non-Sterile

Preparation: solution.

Only pharmacopoeial quality reagents should be used(e.g. The International Pharmacopoeia) and not technical grade products.

B. LABELING

The bottles should be labelled in accordance with national guidelines. Labels should include the following:• Name of institution• Date of production and batch number• Composition: ethanol or isopropanol, glycerol and hydrogen

peroxide (% v/v can also be indicated) and the following statements:• WHO-recommended handrub formulation• For external use only• Avoid contact with eyes• Keep out of reach of children• Use: apply a palmful of alcohol-based handrub and cover all

surfaces of the hands. Rub hands until dry. Flammable: keep away from flame and heat.

Ingredients Quantity

Isopropyl alcohol (with a purity of 99.8%) 751.5 mL

H2O2 3% 41.7 mL

Glycerol 98% 14.5 mL

Distilled water, qs 1000 mL

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Other Formulations

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I. Ethanol 70% (m/m)

A. METHOD OF PREPARATION

1. In a suitable container, mix ethyl alcohol and water. Shake.2. Leave to stand until the bubbles are completely eliminated

and check the ethanolic titre of the solution

C. PRESERVATION, PACKAGING AND STORAGE

• In a suitable container, made of amber glass or high-density opaque plastic, perfectly closed and protected from light, at room temperature.

E. STANDARD OPERATING PROCEDURE FOR QUALITY CONTROL

• Quality-control assessment can include alcohol titre, density, and physical appearance (color, uniformity). Moreover, the absence of microbial contamination (including spores) can be checked by filtration, according to the European Pharmacopeia specifications.

D. STABILITY

• A beyond-use date of 180 days can be used for this prepara-tion when stored in room temperature (USP <<795>>).

DOSAGE FORM: solution

USE/TYPE:Human use. Non-Sterile

Preparation: solution.

B. LABELING

• Keep away from heat sources. • Keep out of the reach of children.• External use.• As an antiseptic, apply to the skin. As a disinfectant, apply to

surfaces or objects to be disinfected.

Ingredients Quantity

Ethanol 96% v/v 75.73g

Distilled water, q.s. 100.0 g

FORMULA:

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III. Hand sanitizer (alcohol gel) with hydroxyethylcellulose

A. METHOD OF PREPARATION

1. Dissolve hydroxyethylcellulose in water. Shake until no lumps are visible.2. Add ethanol and glycerin.3. Bring the volume with water.

C. PRESERVATION, PACKAGING AND STORAGE

• In a suitable plastic container, well closed, protected from light and temperature below 25 ºC.

E. STANDARD OPERATING PROCEDURE FOR QUALITY CONTROL

• Quality-control assessment can include alcohol titre, density, viscosity, and physical appearance (color, uniformity). Moreover, the absence of microbial contamination (including spores) can be checked by filtration, according to the European Pharmacopeia speci-fications.

D. STABILITY

• A beyond-use date of 180 days can be used for this prepara-tion when stored in room temperature (USP <<795>>).

DOSAGE FORM: gel

USE/TYPE:Human use.

Non-Sterile Preparation: gel (fluid, transparent).

B. LABELING

• Keep out of the reach of children.• External use.• As an antiseptic, apply to the skin. As a disinfectant, apply to

surfaces or objects to be disinfected.

FORMULA:

Ingredients Quantity

Ethanol 96% v/v 75.73 g

Hydroxyethylcellulose* 2.5 – 4.0 g

Glycerin 3.0 g

Distilled water, q.s. 100.0 g

*Natrosol™ 250 HHR

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A. METHOD OF PREPARATION

1. Dissolve hydroxypropylmethylcellulose in water with inten-sive agitation to prevent the formation of lumps.

2. Add ethanol and glycerin.3. Bring the volume with water.

C. PRESERVATION, PACKAGING AND STORAGE

• In a suitable plastic container, well closed, protected from light and temperature below 25 ºC.

E. STANDARD OPERATING PROCEDURE FOR QUALITY CONTROL

• Quality-control assessment can include alcohol titre, density, viscosity, and physical appearance (color, uniformity). Moreover, the absence of microbial contamination (including spores) can be checked by filtration, according to the European Pharmacopeia speci-fications.

D. STABILITY

• A beyond-use date of 180 days can be used for this prepara-tion when stored in room temperature (USP <<795>>).

DOSAGE FORM: gel

USE/TYPE:Human use.

Non-Sterile Preparation: gel (fluid, transparent).

B. LABELING

• Keep out of the reach of children.• External use.• As an antiseptic, apply to the skin. As a disinfectant, apply to

surfaces or objects to be disinfected.

FORMULA:

Ingredients Quantity

Ethanol 96% v/v 75.73 g

Hydroxypropylmethylcellulose (minimum 1500 cps) 2.0 – 4.0 g

Glycerin 1.0 - 3.0 g

Water, q.s. 100.0 g

IV. Hand sanitizer (alcohol gel) with hydroxypropylmethylcellulose

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References

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