Oral liquid antibiotic formulations with the focus on organoleptic properties that impact paediatric acceptability
Loading...
Files
Full Text E-thesis
Date
2025
Authors
Elgammal, Ayat
Journal Title
Journal ISSN
Volume Title
Publisher
University College Cork
Published Version
Abstract
Palatability, ‘the overall appreciation of a drug in relation to its smell, taste, aftertaste, texture and appearance’, is a key element influencing paediatric medicine acceptability. Nonadherence to antibiotic treatment because of poor palatability can cause disease recurrence and may contribute to increasing rates of antimicrobial resistance. While the relationship between a medicine’s acceptability and taste has been widely explored, the relationship between a medicine’s odour and its acceptability has received less investigation.
Initially, a questionnaire study was conducted to explore General Practitioners’ (GPs’) and pharmacists’ experiences of prescribing and dispensing oral liquid antibiotics for children respectively in Ireland. Study findings highlight that palatability issues caused GPs and pharmacists to switch oral liquid antibiotics to ensure treatment adherence despite their preference to follow the guidelines and select a first-choice antibiotic. Flucloxacillin was highlighted as the least palatable oral liquid antibiotic for children with a malodour.
Subsequently, an interview study was conducted to obtain a deeper and richer understanding of the experience, attitudes, and challenges faced by GPs and pharmacists. Both professions reported that in some circumstances such as the type of infection, lack of alternatives, and allergies they had to select an unpalatable antibiotic despite knowing that it has poor palatability. Both professions reported that they had never started the palatability discussion with parents to avoid negotiation because of the lack of alternatives. The study findings highlighted the importance of proactive dialogue discussing antibiotic palatability with parents and carers during prescribing and prior to dispensing.
A human sensory study was conducted to assess the odour acceptability of a range of oral flucloxacillin formulations by healthy adult volunteers. The odour of the commercial flucloxacillin solution and capsule formulations were rated acceptable. The commercial solution odour was described as fruity, and aromatic, while the commercial capsule was described as odourless. An unformulated flucloxacillin aqueous solution, and flucloxacillin formulated as minitablets, were deemed to have an unacceptable odour. Their odour was described as pungent, musty, plastic, and rotten. However, the odour of the flucloxacillin minitablet formulation, with silica incorporated as an odour suppressant, was described as odourless and deemed to be acceptable.
Finally, Gas chromatography - mass spectrometry (GC-MS) was used to identify the Volatile Organic Compounds (VOCs) associated with flucloxacillin’s malodour. Two sampling techniques, Head Space (HS) and Solid Phase Microextraction (SPME), were investigated to detect VOCs in the headspace above flucloxacillin samples. The direct HS sampling detected two volatile compounds in flucloxacillin powder of which decane has a particular malodour that could contribute to the overall malodour of flucloxacillin. SPME analysis detected a greater number of VOCs of which octane, decane, undecane, toluene, and styrene are associated with a malodour that can contribute to the overall malodour of flucloxacillin. Interestingly, while the malodour of flucloxacillin was initially thought to be related to its sulfur content, dimethyl disulfide was the only volatile sulfur compound detected and only detected in the aqueous flucloxacillin solution headspace. Dimethyl disulfide can result from degradation of ethynthiol which is one of the flucloxacillin degradation-related VOC impurities.
In conclusion, poor palatability caused GPs and pharmacists to switch oral liquid antibiotics to ensure treatment adherence. Flucloxacillin was identified as a poorly palatable antibiotic with a malodour. Human volunteers associated the odour of unformulated aqueous flucloxacillin solution and minitablets with the descriptors musty, pungent, plastic, and rotten and unacceptable. The odour of a commercial solution was described as acceptable, fruity and aromatic whereas, commercial capsules and minitablets with silica were deemed acceptable and odourless. GC-MS using SPME analysis was used to identify the chemical origin of the malodour described in the human sensory study. A number of volatile compounds which could contribute to the overall flucloxacillin malodour were detected. However, future work is needed to quantify the volatile sulfur compounds (VSCs) associated with flucloxacillin’s overall odour and inform an odour suppression formulation strategy based on component chemistry.
Description
Keywords
Antibiotics , Oral liquid formulation , Palatability , Paediatrics , Odour , Human sensory study , Flucloxacillin , Acceptability
Citation
Elgammal, A. M. M. M. 2025. Oral liquid antibiotic formulations with the focus on organoleptic properties that impact paediatric acceptability. PhD Thesis, University College Cork.