Turner, Roy Maxwell; (2009) Cyclodextrins for oral liquid paediatric drug delivery: Application to corticosteroids. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In the present research, the ability of cyclodextrins (CDs) to solubilise and taste mask poorly soluble bitter drugs was assessed by various analytical techniques, including a novel in vitro taste analyser, to propose CDs as excipients for oral liquid paediatric formulations. Corticosteroids were selected as model drugs because of their relevance in paediatrics, whilst model bitter drug quinine was also selected to provide comparative data. Aside from various inclusion complex characteristics, such as stability constants and complexation efficiencies, phase solubility studies determined that: the CDs formed soluble 1:1 inclusion complexes with the corticosteroids studied, the CD derivatives were capable of providing adequate paediatric dose volumes, simulated media in vivo and pH did not to have a major influence on inclusion complexation. The presence of preservatives, however, reduced CD solubility efficiency, whilst reducing the preservative efficiency. ITC studies determined that inclusion complexation with corticosteroids was a spontaneous process and various interactions involved with complexation were proposed. 1H NMR spectroscopy studies indicated that CDs formed inclusion complexes with the corticosteroids, whereby the drug molecules entered the CD cavities via the wider cavity opening. Human taste panel studies demonstrated that CDs were able to taste mask corticosteroids, often more efficiently than traditional taste masking agents, and with 10 times more drug being incorporated in the formulation. Excess CD was also observed to be more efficient at taste masking corticosteroids than molar equivalent concentrations. From these taste panel results, a mechanism of CD taste masking was proposed. Preliminary electronic tongue analysis was found to be able to select concentrations of various taste masking agents for subsequent taste masking assessment. Nevertheless, little correlation was found between the assessment of the electronic tongue and the human taste panel, thus limiting the legitimacy of the instrument for this application. This research has shown that CDs could be utilised in oral liquid paediatric formulations to provide dose uniformity, appropriate volume, and acceptable palatability for poorly soluble bitter drugs. Further work is required to examine the acceptability & bioavailability of these formulations in paediatric patients.

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