Desai, Neel; (2023) Conventional and novel techniques to measure (oro)dispersible dosage form acceptability: Expanding the formulator's toolbox. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Age-appropriate oral dosage forms must satisfy safety, efficacy, quality, manufacturability and acceptability requirements. Poorly acceptable medicines are associated with poor compliance and can negatively impact therapeutic outcomes. Acceptable paediatric oral dosage forms that consider specific acceptability requirements of children is an unmet clinical need. Formulators rely on human panel studies in early drug product development to examine oral dosage form acceptability attributes. In vivo assessment of multiple acceptability attributes including dispersible and orodispersible [(oro)dispersible] mouthfeel, palatability and swallowability is costly and current in vitro approaches, not robust. Novel in vitro techniques and modified conventional tests may improve understanding of oral physiological processes. In vivo sensory study data could verify early in vitro dosage form acceptability assessments. This combined dataset may inform formulators towards acceptable drug product design. The overall research aims were: to identify barriers to acceptable paediatric (oro)dispersible medicines development, to explore in vitro methods, including novel, physiologically relevant approaches to predict (oro)dispersible mouthfeel, palatability and swallowability and to develop a mobile app (Meet PAT) which collects accurate and real-time questionnaire data during in vivo acceptability studies. Imaging, particle size distribution, fineness of dispersion, insoluble particle fraction, viscometry, rheology, International Dysphagia Diet Standardisation Initiative (IDDSI) flow, texture analysis, bio-tribology and Oral Cavity Model (OCM) in vitro tests were used to examine (oro)dispersible acceptability attributes. Experimental and human panel data were combined to generate a predictive model, known as the surrogate screening tool. Initial dosage form acceptability could be determined using bio-tribology. Less palatable excipients could be identified by dispersion insoluble particle fraction and median particle size. Fineness of dispersion provided good correlation for acceptable dispersions examined in vivo. OCM and IDDSI flow tests could be indicative of viscous dispersions. Both versions of Meet PAT were positively received by adults and children. The terms ‘taste’, ‘flavour’ and ‘sweetness’ were well recognised by children. ‘Grittiness’, ‘mouthfeel’ and ‘texture’ were less understood; a single question encompassing these terms may enable independent sample assessment by children.

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