In preparation for this weeks practical session, we would like you to think about the use of flavourings in oral liquid medicines. Are the flavouring only used to make the medicine taste nice or is there more to it than that? Do some flavouring have a therapeutic use and do some flavourings mask the taste of certain medicines better than others? Are there any incompatibilities between certain flavours and the active product ingredient?
These are a few of the questions that could be asked about flavourings so have a think, see what information you can find and share your thoughts with the group.
Are the flavouring only used to make the medicine taste nice or is there more to it than that?
ReplyDeleteFlavouring play an important role in patient acceptability, especially in oral liquid formulations, and flavours may be necessary to achieve this goal. Frequent and/or high doses of sweetening agents should be avoided in paediatric formulations. The potential laxative effect of polyols (e.g. sorbitol, mannitol) should be considered, along with their osmotic properties and their potential effects on bioavailability.
Do some flavouring have a therapeutic use and do some flavourings mask the taste of certain medicines better than others?
Inactive ingredients i.e. artificial flavourings are components of a drug product that do not increase or affect the therapeutic action of the active ingredient, which is usually the active drug. However, extracts used as flavouring can have a therapeutic action.
Peppermint is used to treat IBS
Clove can be used for its antiseptic and analgesic effects.
Menthol is a flavouring which has a local anaesthetic effect.
Cinnamon is used to combat microorganisms, diarrhoea and other GI disorders, and dysmenorrhea.
Adjusting the taste of active substances:
- Formulating a suspension from the slightly soluble salt or less soluble component. Examples are, taking ferrous fumarate instead of ferrous sulfate.
- Decreasing the dissociation, e.g. the bitter taste of magnesium ion. The addition of dilute sulfuric acid reduces the dissociation and the number of free magnesium ions, thereby improving the taste.
Salty taste is masked by cinnamon, raspberry, orange, maple, butterscotch, glycyrrhiza (licorice) syrup.
Sweet taste is masked by fruit, berry, vanilla, acacia syrup
Bitter taste is masked by cocoa, chocolate-mint, wild cherry, walnut, glycyrrhiza (licorice), eriodictyon, raspberry syrup
Sour taste is masked by fruit, citrus, cherry syrup
Incompatibilities in oral liquids can take place between active substances and excipients i.e. sweeteners. It may regard to formation of insoluble salts or adsorption by thickening agents. Another type of incompatibility is the change of pH brought about by an active substance, causing the flavouring to becoming ineffective. Well-known is the incompatibility of negatively charged thickening agents (carmellose sodium, xanthan gum) with positively charged active substances or excipients.
EMA, August 2013. Committee for Medicinal Products for Human Use (CHMP) Paediatric Committee (PDCO) /CHMP/QWP/805880/2012 Rev. 2
Website link: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/07/WC500147002.pdf Assessed on 04/03/17
Bouwman-Boer, Y., Fenton-May, V. and Le Brun, P. (2015). Practical Pharmaceutics. 1st ed. Cham:
Springer International Publishing.
Flavourings are used in liquid medicine to improve patient’s adherence to the treatment (Gee, 2007). It could be difficult for parents to administer the medication for young children if the medicine is bitter or has a weird taste.
ReplyDeletePeppermint oil could be used to relief stomachache and the feeling of fullness in patients with irritable bowel disease (BNF, 2017).
Menthol could be used as a flavouring in cigarettes. However, more research has to be done to explain how the cooling and anesthetic effect of menthol may modify normal cigarettes consumption. Also, menthol could possibly influence the uptake of nicotine and lead to irritation/ toxicity (Wayne, 2004).
The pharmaceutical industry is also choosing flavourings according to the target patient groups. Sweet and fruity flavourings would be preferred by younger patient groups while adult may prefer tart flavours. Minty flavourings would be preferred by older patient groups and citrus flavourings are commonly added into medication that would be administered repeatedly. These flavourings have different chemical structures that give the taste variation, for example OH groups attached give a sweeter taste to organic compounds and the volatility of alcohol gives a cooling and likeable taste (UNC, 1996).
Excipients are used in manufacturing oral liquid medicine to improve stability. These additives, including flavourings, may interact with each other and the supporting data of final product stability is insufficient.
When hydralazine hydrochloride was mixed with Ora-Sweet and cherry syrup, the final product was not stable. When hydralazine was mixed with simple syrup, the hydrolysed sucrose also led to a significant drug lost (Glass, 2006). Therefore, the choice of flavourings is not only effective for masking the taste of active ingredients, but influentially crucial in product stability.
S. Gee and T. Hagemann (2007) J Pediatr Pharmacol Ther. 12(4): 216–223. Palatability of Liquid Anti-Infectives: Clinician and Student Perceptions and Practice Outcomes [Online] Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462086/
British National Formulary (2017) 1.2 Antispasmodics and other drugs altering gut motility [Online] Available at: https://www.evidence.nhs.uk/formulary/bnf/current/1-gastro-intestinal-system/12-antispasmodics-and-other-drugs-altering-gut-motility/other-antispasmodics/peppermint-oil
F. Wayne and G. Connolly (2004) Nicotine Tob Res. 6(1): 43-54. Application, function, and effects of menthol in cigarettes: a survey of tobacco industry documents. [Online] Available at: https://www.ncbi.nlm.nih.gov/pubmed/14982708
UNC Eshelman School of Pharmacy (1996) The Pharmaceutics and Compounding Laboratory: Aesthetic Considerations of Oral Liquid Dosage Forms [Online] Available at: http://pharmlabs.unc.edu/labs/aesthetic/palatability.htm
B. Glass and A. Haywood (2006) J Pharm Pharmaceut Sci 9(3):398-426. Stability considerations in liquid dosage forms extemporaneously prepared from commercially available products. [Online] Available at: https://sites.ualberta.ca/~csps/JPPS9_3/MS_973_Review/MS_973.html
The vast majority of oral solutions are unpalatable and therefore require a flavoring to mask the taste.
ReplyDeleteThe four basic taste sensations are salty, sweet, bitter and sour and the type of sensation determines the type of flavoring used.
1) Salty: butterscotch, apricot, peach, vanilla and wintergreen mint
2) Bitter: cherry, mint and anise
3) Sweet: vanilla and berry fruits
4) Sour: citrus fruits and raspberry
These Flavourings are often used in combination, in order to achieve the desired taste.
Other excipients called flavor adjuncts such as methanol and chloroform, not only add flavour to the solution, but also desensitise taste receptors. By doing this these excipients improve the taste, masking properties of conventional flavours.
Jones, D. (2008) Pharmaceutics Dosage Form and Design. Pharmaceutical Press. London (This book contained information on the preparation of oral solutions, detailing the excipients used and their use)
ReplyDeleteFlavours are commonly used in pharmaceutical oral solutions and oral suspensions to mask drug bitterness and to make the formulation more palatable. Cough syrups, laxatives, sedatives antihistamines, antibiotics, vitamins and paediatric and geriatric formulations now are available in a variety of flavours which successfully mask unpleasant tastes without affecting physical and chemical stability which therefore increases patient compliance
Different flavours are used to disguise different pharmaceutical excipients;
an orange-mint flavour is especially effective in disguising diphenhydramine in an expectorant formulation. Maple combined with butterscotch is well suited to improve the taste of adsorbents such as kaolin and pectin. Mint is preferred in antacid preparation.
Flavour acceptance is also affected by age. In general, children like fruit flavoured syrup, adults prefer a more acid taste, while many old people find mint or wine flavours more agreeable.
Although this article is very old, I think it makes some interesting points bout the detail that goes into using different flavours in pharmaceutical preparations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331350/pdf/ASL-8-38.pdf
Flavourings
ReplyDeleteFlavourings are used in medicines to improve taste and patient compliance. The basic ingredients of medicinal products do not provide and acceptable taste or smell, and therefore required the addition of flavourings. (Action on Additives, 2017)
Flavourings are inactive ingredients which are mainly used in oral preparations such as syrups, chewable tablets, suspensions, or gums to improve taste and colour of the medicine. (Drugs.com, 2017)
They can be used to mask specific taste sensations such as: salty, bitter, sweet, and sour tastes, and the flavours that are used are as follows:
Salty: butterscotch, apricot, peach, vanilla, wintergreen mint
Bitter: cherry, mint, anise
Sweet: vanilla, fruit and berry
Sour: citrus flavours, raspberry
(Jones, 2016)
References:
- Action on Additives. (2017). Flavourings. [online] Available at: http://www.actiononadditives.org/flavourings/ [Accessed 10 Mar. 2017]
- Drugs.com. (2017). Flavor (Inactive Ingredient) - Drugs.com. [online] Available at: https://www.drugs.com/inactive/flavor-218.html [Accessed 10 Mar. 2017]
- Jones, D. (2016). Pharmaceutics - Dosage Form and Design. 1st ed. London: Pharmaceutical Press, pp.14-15.
The palatability of oral liquid medicines is important, as if palatability is poor, this may lead to non-compliance. The smell and taste of a product are important in getting children to comply with their medicines. (Gee and Hagemann, 2007) Hence, oral liquid medicines are flavoured with synthetic or naturally occurring flavourings. Care is taken to ensure that the flavouring does not affect stability of the product. The colour of the product is also changed at times to match the flavoring, such as red to go with cherry flavor, care is taken to ensure that the colouring does not affect product stability. Flavourings such as sweeteners are used in products to conceal the taste of the drug in a solution. Sweeteners can also increase the viscosity of solution, hence may be sometimes used for this. (Ghosh and Jasti, 2004) Flavouring is also important in enhancing the texture of the product, to give a more pleasant feeling in the mouth. Examples of additives that are used in practice to affect the flavor of a product include
ReplyDelete• Citric Acid BP which masks bitter tastes and improves the capability of citrus flavours to mask acid tastes
• Menthol BP and Peppermint Oil BP have some anaesthetic action locally, hence numb the taste buds, which is an example of a therapeutic use of flavourings.
• Sodium Chloride BP and Sodium Citrate help to reduce bitterness of the product.
Some flavourings are able to mask the taste of certain medicines better than others such as:
• A bitter taste of medicines can be masked by anise, mint, passion fruit, wild cherry or chocolate flavourings.
• A salty taste of medicines can be counterbalances by apricot, liquorice, peach, butterscotch, or vanilla.
• A sour taste can be disguised by using citrus fruits, liquorice or raspberry flavourings.
• Sweetness can be dampened by using vanilla, fruits or berries. (Marriott, 2010)
Flavourings such as peppermint have good antiseptic, antibacterial and antiviral properties which can reduce mucus, relieve coughs and throat infections. It also has soothing and anti-spasmodic effects which enable it to relieve heartburn and acidity. (Thosar et al., 2013)
The agents used for flavouring can be natural or artificial, natural flavours tend to have many different types of molecules which can cause interference with the active pharmaceutical ingredient. (Bouwman, Fenton-May and Le Brun, 2015) The industry has recognized that cherry flavours with benzaldehyde interact with active ingredients containing an amine group, and grape flavours containing methylanthranilate interact with active ingredients containing a carbonyl group. These interactions leas to the loss of flavor and active ingredient. Hence, the industry has learned to eliminate the benzaldehyde from the cherry flavor and the methylanthranilate from the grape flavor. (Schmidl and Labuza, 2000)
Bouwman, Y., Fenton-May, V. and Le Brun, P. (2015). Practical Pharmaceutics An International Guideline for the Preparation, Care and Use of Medicinal Products. 1st ed. Springer International Publishing, p.58.
Gee, S. and Hagemann, T. (2007). Palatability of Liquid Anti-Infectives: Clinician and Student Perceptions and Practice Outcomes. J Pediatr Pharmacol Ther, [online] 12(4). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462086/pdf/i1551-6776-12-4-216.pdf [Accessed 31 Mar. 2017]
Ghosh, T. and Jasti, B. (2004). Theory and Practice of Contemporary Pharmaceutics. 1st ed. London: CRC Press, p.378.
Marriott, J. (2010). Pharmaceutical compounding and dispensing. 1st ed. London: Pharmaceutical Press, pp.89-91.
Schmidl, M. and Labuza, T. (2000). Essentials of functional foods. 1st ed. Gaithersburg: Aspen Publishers, p.93.
Thosar, N., Basak, S., Bahadure, R. and Rajurkar, M. (2013). Antimicrobial efficacy of five essential oils against oral pathogens: An in vitro study. European Journal of Dentistry, [online] 7(1). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054083/ [Accessed 31 Mar. 2017].