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Soothing Properties of Glycerol in Cough Syrups for Acute Cough Due to Common Cold

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Ronald Eccles at Cardiff University
Ronald Eccles
Pascal Mallefet
Pascal Mallefet
Pascal Mallefet
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Abstract

The treatment and management of acute cough due to common cold costs billions of dollars of healthcare expenditure and there is a growing opinion that a simple linctus containing glycerol with flavourings such as honey and lemon is a safe and effective treatment for acute cough in children and adults. Glycerol is a component of most cough syrups, and although it is often thought of only as a solvent or thickening agent in cough syrups, it may be a major component for the efficacy of cough syrups due to its special properties of lubrication, demulcency, sweetness, and acting as a humectant. The major benefit of cough syrups in soothing cough is likely due to the properties of the syrup rather than the active ingredients and this review discusses the special properties of glycerol in relation to the treatment of acute cough.
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pharmacy
Review
Soothing Properties of Glycerol in Cough Syrups for
Acute Cough Due to Common Cold
Ronald Eccles 1, * and Pascal Mallefet 2
1Common Cold Centre, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
2Novartis Consumer Health SA, a GSK consumer Healthcare Company, 1260 Nyon, Switzerland;
pascal.x.mallefet@gsk.com
*Correspondence: eccles@cardiff.ac.uk; Tel.: +44-29-2087-4102
Academic Editor: Ieva Stupans
Received: 1 December 2016; Accepted: 17 January 2017; Published: 20 January 2017
Abstract:
The treatment and management of acute cough due to common cold costs billions of dollars
of healthcare expenditure and there is a growing opinion that a simple linctus containing glycerol
with flavourings such as honey and lemon is a safe and effective treatment for acute cough in children
and adults. Glycerol is a component of most cough syrups, and although it is often thought of only as
a solvent or thickening agent in cough syrups, it may be a major component for the efficacy of cough
syrups due to its special properties of lubrication, demulcency, sweetness, and acting as a humectant.
The major benefit of cough syrups in soothing cough is likely due to the properties of the syrup rather
than the active ingredients and this review discusses the special properties of glycerol in relation to
the treatment of acute cough.
Keywords: acute cough; cough syrups; glycerol
1. Introduction
Glycerol, referred to as glycerine or glycerin in the United States, is one of the most versatile and
commonly used chemicals in the pharmaceutical, cosmetic and chemical fields and it is quoted as
having over 1500 known end uses [
1
,
2
]. Glycerol is found naturally in all living cells in the form of
triglycerides and it occurs naturally in wines, beers, breads and most products of fermentation [
3
].
Quoting C.E. Gentry, Procter & Gamble Co. (Cincinnati, OH, USA) glycerol product manager in 1984,
“Glycerol may be the most versatile chemical known to man. It is used to make glue to stick things
together, and in dynamite to blow things apart. It is used in cough suppressants and suppositories.
Glycerol is used in hair sprays and house paint. It is an ingredient in expensive liqueurs and cheap pet
foods” [
4
]. Glycerol is a component in most cough syrups. It is often thought of only as a solvent or
thickening agent; however, it also contributes to the efficacy of the cough treatment due to its special
properties of lubrication, demulcency, sweetness, and acting as a humectant.
This short review will focus on the role of glycerol as an important component for the efficacy of
cough syrups.
2. Special Properties of Glycerol
Glycerol (1,2,3-propanetriol) as shown in Figure 1is a colourless, odourless, viscous liquid with
a warm sweet taste.
Pharmacy 2017,5, 4; doi:10.3390/pharmacy5010004 www.mdpi.com/journal/pharmacy
Pharmacy 2017,5, 4 2 of 5
Pharmacy 2017, 5, 4 2 of 5
Figure 1. Chemical structure of glycerol.
Glycerol is obtained from natural sources such as animal fats and also as a side product of the
soap and petrochemical industries. In its pure anhydrous state, glycerol has a specific gravity of 1.261
gmL-1, a melting point of 18.2 Centigrade, and a boiling point of 290 Centigrade [2,3]. Glycerol
contains three hydrophilic alcoholic hydroxyl groups which make it very soluble in water and also
account for its hygroscopic properties and behaviour as a humectant. Humectants are substances that
retain moisture and in turn give softness, and this hygroscopic property of glycerol makes products
containing glycerol, such as lotions and syrups, soft, flexible, and creamy [3]. Glycerol is added to
many products because of its ability to attract and hold water and this is the part of its humectant
property that is so useful in cosmetics, especially skin products, which are marketed for their
moisturizing action [1]. The humectant property of glycerol may at first seem at odds with its
moisturizing action, but it is the property of glycerol to hold water close to the skin that provides the
moisturizing effect and not the withdrawal of water from skin tissue [1].
Glycerol contributes a plasticizing effect, as glycerol and water act together to promote softness
and flexibility, and a hydrating effect is achieved as the glycerol solution prevents drying out. This
plasticizing or humectant effect is beneficial for products such as cosmetics, creams, lotions, tooth
pastes, candy, cough drops and cough syrups [3]. Because of its hydroxyl groups, glycerol has
solubility characteristics similar to those of water and simple aliphatic alcohols and this makes it a
very useful solvent for cough medicines. Glycerol is viscous and has a high viscosity and this makes
it useful as a thickening or bodying agent which gives viscosity to cough syrups. At normal
temperatures, glycerol is a stable viscous liquid right up to concentrations of 100% without any
crystallization. Glycerol is also a lubricant as it decreases the friction between moving surfaces, and
for this reason, glycerol is used as a lubricant in artificial tears and also as an industrial lubricant in
air compressors [2].
Glycerol has demulcent properties with the term demulcent meaning soothing (derived from
the Latin demulcere, “caress”). A demulcent is a substance that forms a soothing film over a mucous
membrane to relieve minor pain and inflammation of the membrane [5]. The demulcent property of
glycerol is particularly useful when it is a component of artificial tears [6] and it contributes to the
efficacy of cough syrups [7,8].
Glycerol is virtually non-toxic in the digestive system and non-irritating to the skin and sensitive
membranes, except in very high concentrations when a dehydrating effect is apparent [3].
3. Acute Cough
Acute cough is commonly caused by viral infections of the upper respiratory tract (URTI) [9].
Cough is normally a protective reflex to prevent the entry of food and fluid into the respiratory tract,
but viral infections then cause inflammation of the upper airways and a sensation of irritation with
an urge to cough which results in coughing that is a nuisance rather than a benefit to the subject [9,10].
The sensation of irritation that causes the urge to cough is due to a hypersensitivity of the sensory
H
C
C
C
H
H
H
H
OH
OH
OH
Figure 1. Chemical structure of glycerol.
Glycerol is obtained from natural sources such as animal fats and also as a side product of
the soap and petrochemical industries. In its pure anhydrous state, glycerol has a specific gravity
of 1.261 g
·
mL
−1
, a melting point of 18.2 Centigrade, and a boiling point of 290 Centigrade [
2
,
3
].
Glycerol contains three hydrophilic alcoholic hydroxyl groups which make it very soluble in water and
also account for its hygroscopic properties and behaviour as a humectant. Humectants are substances
that retain moisture and in turn give softness, and this hygroscopic property of glycerol makes products
containing glycerol, such as lotions and syrups, soft, flexible, and creamy [
3
]. Glycerol is added to many
products because of its ability to attract and hold water and this is the part of its humectant property
that is so useful in cosmetics, especially skin products, which are marketed for their moisturizing
action [
1
]. The humectant property of glycerol may at first seem at odds with its moisturizing action,
but it is the property of glycerol to hold water close to the skin that provides the moisturizing effect
and not the withdrawal of water from skin tissue [1].
Glycerol contributes a plasticizing effect, as glycerol and water act together to promote softness
and flexibility, and a hydrating effect is achieved as the glycerol solution prevents drying out.
This plasticizing or humectant effect is beneficial for products such as cosmetics, creams, lotions,
tooth pastes, candy, cough drops and cough syrups [
3
]. Because of its hydroxyl groups, glycerol has
solubility characteristics similar to those of water and simple aliphatic alcohols and this makes it a very
useful solvent for cough medicines. Glycerol is viscous and has a high viscosity and this makes it useful
as a thickening or bodying agent which gives viscosity to cough syrups. At normal temperatures,
glycerol is a stable viscous liquid right up to concentrations of 100% without any crystallization.
Glycerol is also a lubricant as it decreases the friction between moving surfaces, and for this reason,
glycerol is used as a lubricant in artificial tears and also as an industrial lubricant in air compressors [
2
].
Glycerol has demulcent properties with the term demulcent meaning soothing (derived from
the Latin demulcere, “caress”). A demulcent is a substance that forms a soothing film over a mucous
membrane to relieve minor pain and inflammation of the membrane [
5
]. The demulcent property of
glycerol is particularly useful when it is a component of artificial tears [
6
] and it contributes to the
efficacy of cough syrups [7,8].
Glycerol is virtually non-toxic in the digestive system and non-irritating to the skin and sensitive
membranes, except in very high concentrations when a dehydrating effect is apparent [3].
3. Acute Cough
Acute cough is commonly caused by viral infections of the upper respiratory tract (URTI) [
9
].
Cough is normally a protective reflex to prevent the entry of food and fluid into the respiratory tract,
but viral infections then cause inflammation of the upper airways and a sensation of irritation with
an urge to cough which results in coughing that is a nuisance rather than a benefit to the subject [
9
,
10
].
The sensation of irritation that causes the urge to cough is due to a hypersensitivity of the sensory
Pharmacy 2017,5, 4 3 of 5
nerves in the upper airway found mainly in the larynx. Cough can also be initiated by pharyngeal
stimulation [
11
] and this indicates that sensory nerves in the pharynx may also be involved in the
generation of cough associated with URTI, as pharyngitis is a common symptom associated with
URTI [12].
4. Mechanism of Action of Glycerol in Soothing Cough
The major effect of cough syrups in soothing cough is due to the properties of the syrup rather
than the active ingredients such as dextromethorphan. Up to 85% of the benefit of cough syrups may
be due to the physical and chemical effects of the syrup which contribute to its demulcent action [7].
Glycerol is a component of many cough syrups, especially in honey and lemon syrups where the
concentration of glycerol is usually around 0.75 g per 5 mL and where glycerol may be declared as the
sole active ingredient of the cough syrup.
The efficacy of glycerol must be related to its physical and chemical properties, as glycerol does
not have any known pharmacological actions.
4.1. Demulcent
Glycerol is often referred to as having demulcent properties [
8
,
13
] and it is commonly used as
an emollient in skin products to soften and soothe skin [
3
]. Glycerol may work as a demulcent in the
pharynx by coating and lubricating the pharyngeal surface. The moisturizing properties of glycerol
may also help to soothe inflamed mucosal surfaces in the pharynx.
4.2. Lubrication
Glycerol has lubricant properties [
8
] and is used as a lubricant in machinery such as air
conditioners and compressors [
2
] and in lubricating cosmetic gels and creams [
14
]. The lubricant
properties of glycerol are beneficial in lubricating the pharyngeal area, as the surfaces of the pharynx
and tongue slide over each other during swallowing and speech and this mechanical stimulation will
irritate sensory nerves that trigger cough. Glycerol will coat the pharynx and act as a lubricant and
reduce the friction between moving surfaces of the pharynx and tongue and therefore sooth cough.
Glycerol may also influence the structure of the protein surface of the pharynx by decreasing the
volume of proteins, and this may contribute to smoothing the surface and a lubricant effect [15].
4.3. Sweetness
Glycerol has a sweet, warm taste and is about 0.6 to 0.8 times as sweet as sucrose [
13
,
16
].
The sweetness of cough syrups has been proposed to be a major factor in their efficacy [
17
]. The sweet
taste in cough syrups has been proposed to modulate cough at the level of the nucleus tractus solitarius,
possibly by influencing the production of endogenous opioids [
17
]. This mechanism for an antitussive
action of the sweet taste has been supported experimentally by demonstrating that rinsing the mouth
with a sweet-tasting solution inhibits capsaicin-induced cough, whereas rinsing with a bitter-tasting
solution had no effect on the cough threshold [18,19].
5. Discussion
The treatment and management of cough costs billions of dollars of healthcare expenditure and
a huge burden in terms of days lost from school and loss of work hours [
20
]. For example, in the
UK, acute cough resulted in an estimated cost of £875 million due to loss of productivity and a cost
of £104 million to the healthcare system along with the purchase of non-prescription medicines [
21
].
Estimating the global prevalence of cough is difficult considering its benign and self-limiting nature.
An estimated 48 million cases of acute cough occur every year in the United Kingdom [21].
In general, over-the-counter (OTC) cough suppressants for acute cough show inconsistent,
variable and conflicting results in terms of clinical improvement and have limited efficacy for
Pharmacy 2017,5, 4 4 of 5
symptomatic relief [
22
–
24
]. Various concerns about their safety include unintentional consumption,
medication overdose and an additive effect due to the intake of cough and cold medications with the
same active ingredients, for example two multi ingredient medicines which both contain paracetamol.
Improper use of OTC cough and cold medication has also resulted in fatalities in children [
25
–
27
].
Considering these points, health authorities such as MHRA, Health Canada and other professional
health bodies do not recommend their use in children below the age of six and the FDA does not
recommend the use of these products in children below four years of age [
22
,
25
–
29
]. Instead, several
health authorities such as MHRA promote the use of a simple cough syrup or linctus containing
glycerol, lemon, and honey, which are soothing, safe and generally cheap [27].
There is, at present, no published research on the efficacy of glycerol as a cough treatment and
there is a need for randomised placebo-controlled clinical trials to determine the contribution of this
common ingredient in cough medicines to the overall benefit of cough medicines.
6. Conclusions
Acute cough is a common condition and there is a growing opinion that a simple linctus containing
glycerol with flavourings such as honey and lemon is a safe and effective treatment for cough in
children and adults.
Conflicts of Interest: The authors declare no conflict of interest.
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©
2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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This commentary responds to a case about diethylene glycol-contaminated glycerin in cough syrup. Glycerin is a commonly used excipient in medicines to improve texture and taste. Excipients are typically pharmacologically inactive ingredients contained in prescription and over-the-counter drugs that play a critical role in the delivery, effectiveness, and stability of active drug substances. The commentary first canvasses how contaminants enter the excipient supply chains. One way is by misleading labeling or intentional adulteration by manufacturers or suppliers. Another way is by human or systemic error. This commentary then discusses quality control testing and suggests the ethical and clinical importance of increased transparency in excipient supply chains.
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... It is believed that the wetting and emollient properties of glycerol significantly contribute to the symptomatic effectiveness of cough syrups. Moreover, since the pharynx and the tongue surfaces slip against each other during swallowing and phonation, and this mechanical stimulation can irritate the sensory nerves and induce coughing, the lubricating property of glycerol is useful for oiling the pharyngeal area providing an antitussive symptomatic action [32]. ...
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Ovotransferrin, an alternative and potential protein for diverse food and nutritional applications
Article
Ovotransferrin(OVT)is a protein found in many types of egg white and has a wide range of functional properties. It has 50% homology with human/bovine lactoferrin, and is expected to be one of the most important alternative proteins for use in food and nutritional applications. This paper mainly reviews the structural characteristics and chemical properties of OVT, as well as its extraction and purification methods. It also systematically describes the various biological activities of OVT and its applications in food and medical industries. The challenges and limitations in the research of OVT were suggested. This review recommends some possible methods such as nanoparticle carriers and microencapsulation to improve the bioavailability and stability of OVT. In addition, this review highlights several strategies to overcome the limitations of OVT in terms of preparation and purification. This review systematically summarizes the recent advances in OVT and will provide guidance for the its development for food and nutritional applications.
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Sindrome da ipersensibilità dei recettori della tosse (SIRT): “la tosse che fa tosse”
Article
  • Sep 2023
Dry cough usually accompanies the first few days of each “cold” (Upper Respiratory Tract Infection: URTI), but in some children, it always recurs with a particular intensity that “prevents sleep” and puts the whole family to the test. This cough is recognized to have an etiopathogenetic factor of an exaggerated sensitivity of cough sensory receptors. In the year 2000, the “Medico e Bambino” journal coined the acronym SIRT (Sindrome da Ipersensibilità dei recettori della Tosse - Cough Receptors Hypersensitivity Syndrome) to label this phenotype of cough. Today, this diagnosis is made more frequently especially by Italian family paediatricians who have learned to understand and recognize it. However, in the paediatric literature, SIRT still lacks recognition and an adequate description of its peculiar clinical characteristics. It is conceivable that SIRT corresponds to the persistent cough during the most acute phase of URTIs. The mechanisms by which viral infections induce the dysregulation of the cough reflex are now well understood, but why it remains unchanged over time in only certain individuals is still unknown. In adulthood, cough due to cough receptor hypersensitivity (Cough Receptor Hypersensitivity, CRH) has received much more attention, becoming an “umbrella” diagnosis for all “chronic” coughs of undefined cause. CRH recognizes the same mechanisms and causes at all ages, but there is a significant clinical difference that, in children, due to the high frequency of URTIs, it is characterized by recurrent episodes of acute cough, while in adults, CRH primarily manifests as a “chronic” cough induced by micro environmental stimuli (thermal, mechanical, chemical).
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Effect of Taste Sensation on Cough Reflex Sensitivity
Article
Full-text available
  • Oct 2013
  • LUNG
Cough is among the most common symptoms with which people present for medical attention, but evidence-based treatments remain limited. One issue compromising interpretation of clinical trials of cough preparations is that control formulations often are nearly as effective as those that contain active ingredients. This observation has caused some researchers to propose that one or more nominally inactive ingredients may have some physiological effects. For example, most liquid cough preparations are highly sweetened, and it has been suggested that sweet taste might modulate cough sensitivity. The fact that honey has been used for thousands of years as a cough remedy is consistent with this idea. However, empirical evidence for modulation of cough sensitivity by taste was lacking. Evidence is still sparse, but relevant experiments have now been published: rinsing the mouth with a sweet sucrose solution increased cough thresholds in a single-inhalation capsaicin challenge. Furthermore, rinsing the mouth with a bitter solution did not affect thresholds, an important demonstration of specificity. The underlying mechanisms of cough suppression by sweet taste are still unclear. However, extant data suggest that modulation of cough sensitivity by taste is a promising area for further investigation. Such work may lead to greater understanding of apparent placebo effects in clinical trials and provide empirical support for therapies based on stimulation of taste nerves.
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Effect of Honey on Nocturnal Cough and Sleep Quality: A Double-blind, Randomized, Placebo-Controlled Study
Article
Full-text available
  • Aug 2012
  • Pediatrics
To compare the effects of a single nocturnal dose of 3 honey products (eucalyptus honey, citrus honey, or labiatae honey) to placebo (silan date extract) on nocturnal cough and difficulty sleeping associated with childhood upper respiratory tract infections (URIs). A survey was administered to parents on 2 consecutive days, first on the day of presentation, when no medication had been given the previous evening, and the following day, when the study preparation was given before bedtime, based on a double-blind randomization plan. Participants included 300 children aged 1 to 5 years with URIs, nocturnal cough, and illness duration of ≤ 7 days from 6 general pediatric community clinics. Eligible children received a single dose of 10 g of eucalyptus honey, citrus honey, labiatae honey, or placebo administered 30 minutes before bedtime. Main outcome measures were cough frequency, cough severity, bothersome nature of cough, and child and parent sleep quality. In all 3 honey products and the placebo group, there was a significant improvement from the night before treatment to the night of treatment. However, the improvement was greater in the honey groups for all the Parents rated the honey products higher than the silan date extract for symptomatic relief of their children's nocturnal cough and sleep difficulty due to URI. Honey may be a preferable treatment for cough and sleep difficulty associated with childhood URI.
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Acute cough: Epidemiology, mechanisms, and treatment
Chapter
  • Jan 2005
stimating the duration of cough is the first step in diagnosis. Obviously all types of cough have an onset and hopefully an end, therefore by definition all types of cough must go through an initial acute stage at the time of onset. Irwin and Madison (1) categorize cough on the basis of duration; acute cough lasting less than 3 weeks, subacute 3-8 weeks, and chronic lasting more than 8 weeks. Most cases of acute cough will not be seen by specialists as the self-limiting nature of the condition means that the cough is likely to have resolved before the patient can obtain an appointment to see the specialist. Morice (2) defines cough into only two diagnostic groups; acute cough that is usually due to viral respiratory tract infection and chronic cough that may be arbitrarily defined as lasting longer than 8 weeks. It is the latter definition by Morice (2) that will be used in the present discussion and acute coughwill be defined as caused by acute upper respiratory tract viral infection. Irwin et al. (3) list other common causes of acute cough such as acute bacterial sinusitis, pertussis, exacerbation of chronic obstructive pulmonary disorder (COPD), allergic rhinitis, and exposure to environmental irritants; and lists less common causes of acute cough as asthma, congestive heart failure, pneumonia, aspiration syndromes, and pulmonary embolism. The present discussion will be limited to acute cough associated with viral infection of the upper respiratory tract.
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Acute and chronic cough
Book
  • Jan 2005
A comprehensive review of the scientific and clinical aspects of acute and chronic cough, this reference focuses on recent developments in our understanding of the molecular biology of putative cough receptors, the neural mechanisms involved in the afferent and efferent limbs, the central processing of the cough reflex, and peptides and other substances that may mediate or modulate the cough reflex. With chapters written by acknowledged authorities in the field, this handbook covers current and potential therapeutic agents, various methodologies to measure cough reflex sensitivity, and clinical approaches for the assessment of chronic cough in adults and children.
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The Future of Glycerol: New Usages for a Versatile Raw Material
Book
  • Jan 2008
By-products of global biodiesel manufacturing are a global fact and the immense amount of glycerol by-product stacking unsold until mid 2005 gave a visual image of the huge loss of energy and material resources. This was due to the lack of suitable conversion processes for this, the oldest organic molecule known to man, despite various experiments by some biodiesel producers. The large surplus of glycerol by-product which entered the chemical market has caused closure of existing glycerol plants and the discovery of processes that use glycerol as a raw material for the production of value-added chemicals and even of energy. This was followed by 3-4 years of intense research activity worldwide, where human chemical ingenuity opened up a number of practical avenues to convert glycerol into value added products of mass consumption.
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Chronic Cough in Children
Article
  • Aug 2013
The management of chronic cough, a common complaint in children, is challenging for most health care professionals. Millions of dollars are spent every year on unnecessary testing and treatment. A rational approach based on a detailed interview and a thorough physical examination guides further intervention and management. Inexpensive and simple homemade syrups based on dark honey have proved to be an effective measure when dealing with cough in children.
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