Development and characterisation of palatable paediatric formulations using novel technologies

  • Samia Farhaj

Student thesis: Doctoral Thesis


For many years, the development of age-appropriate formulations for the paediatric population is considered challenging due to additional dosing requirements and diversity in their developmental phase. To counteract this problem, conventional adult formulations are prescribed as off-label or manipulated according to the individualised dosing requirement. In terms of drug delivery, oral route remained the most convenient way of drug administration even in paediatric patients. But after oral administration differences in the physiology of paediatrics compared to adults have been seen to influence directly on the pharmacokinetic profiles of the drug. Therefore, it is essential to identify such differences to provide better information during paediatric-specific formulation development, whilst ensuring effective and safe concentration of therapeutically active substances. For this reason, a comprehensive literature review was conducted that sheds light on gastrointestinal tract features and discusses the physiological and anatomical differences among paediatric and adults. Secondly, a systematic review was conducted to understand the recent progress and development of orally disintegrating tablets (ODTs) for the paediatric population covering the findings of the last nine years. Thirdly, a literature review on the applications of nanofibres in drug delivery was conducted to understand their potential advantages while comprehending different nanofibre production methods. Lastly, a cent-hydro system was introduced which is synchronised with temperature and pressure to fabricate nanofibre mats at large scale and to provide a novel platform in oral drug delivery application for paediatric patients.

The literature review discussed the importance of physiological differences that need to be identified initially to provide better information during formulation development for children. Furthermore, children usually exhibit distinctive preferences in terms of acceptability of oral formulations, therefore, it is essentially important to develop such types of oral formulations which are palatable, require minimal dosing interval and are easy to administer covering all subsets of the paediatric population.

The systemic review was conducted by following PRISMA guidelines to evaluate the recent progress in ODTs development, particularly targeting the paediatric population. A total of 45 studies were included and they were discussed based on fabrication methods, types of disintegrants used and disintegration tests employed. The findings from current systematic review will be helpful for the researchers in future to develop ODTs by incorporating other drugs.

Another literature review was conducted to potentially highlight the importance of nanofibres in developing drug delivery systems exhibiting tuneable drug release kinetics. The review sheds a light on the traditional and emerging techniques which are successfully employed for nanofibres fabrication. But apart from numerous investigations, the fabrication of nanofibres is still limited to the laboratory scale due to technological limitations and formulation challenges.

A novel low-cost nanofibre manufacturing system (cent-hydro) was developed to fabricate nanofibres at a large scale. The system was initially calibrated experimentally through the finger study. The increase in working temperature and rotational speed increased the finger length and finger velocity. The increase in motor speed at constant working pressure and temperature decreased the diameter of the nanofibres. Also, with an increase in the content of PEO in the solution the size and production yield of nanofibres was increased but beyond the percentage of 20%, the effect become insignificant statistically. The increase in working temperature at constant working pressure and rotational speed decreased the diameter of nanofibres but the difference between the diameters produced at 50 °C and 60 °C was not statistically significant. The nanofibres produced from this novel technique had higher production yield compared to previous systems. In conclusion from these findings, this system has a high potential for industrial applications.

PCM-loaded wafers were developed to improve the dissolution profile and to overcome the challenges of conventional formulations available for paediatric patients. The nanofibres were successfully developed from cent-hydro system under constant temperature, working pressure and rotational speed. The PCM-loaded nanofibres after compression into wafers possessed nano-web structure. From in vitro dissolution studies the optimised formulations depicted faster drug release in comparison to other formulations in both dissolution mediums (salivary fluid and 0.1M HCL). From these findings, nanofibres could be used as a potential matrix in future for the development of wafers with poorly soluble drugs.
Date of Award16 Aug 2023
Original languageEnglish
SupervisorMuhammad Usman Ghori (Main Supervisor) & Barbara Conway (Co-Supervisor)

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