Development of a multiparticulate-based platform for delivering functionalised capability as an oral liquid dosage form

• Main Author: Bowles, A. F.
• Published: University College London (University of London) 2013
• Subjects: 615.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626341

That ‘Children are not small adults’ is a commonly quoted adage: nowhere is this more true than in pharmaceutics. When trying to make an “age-appropriate” oral dosage form, a number of patient needs must be met including swallowability, dose-adaptability and acceptability. Acceptability may be enhanced by better tasting, non-gritty medicines: with this in mind this research sought to develop a suspension platform for functionalised multiparticulates, namely for taste-masking. The rheology of the suspending media and its effect on the suspendability of large (>100 μm) placebo particles was investigated before the influence of particle concentration, size and media viscosity of these suspensions on grittiness and acceptability was assessed in two sensory trials containing young adults. It was found that higher concentrations of hydoxypropylmethycellulose were not well tolerated due to their inherent taste and that their acceptability was improved through the addition of flavouring/sweetening agents. Statistical analysis of the results on the refined media and sensory trial showed that particle size and media viscosity had an effect on grittiness, unlike particle concentration. Microparticles of Eudragit® E (a reverse-enteric polymer marketed for taste-masking) containing quinine hydrochloride as a bitter drug were prepared by spray-drying without using organic solvents. Initial experiments resulted in many blockages of the spray dryer which were eventually rectified by increased homogenization and a fractional factorial experimental design employed to screen the influence of different levels of excipients. However, even the optimised process suffered from problems with a low feed solids concentration, low spray rate and low yield. Most particles had an aggregated morphology and the formulations which showed the lowest release in salivary pH were the most aggregated with particle sizes >1 mm. These large particles were not easy to uniformly suspend and would have required a large mass to be administered due to low drug loading which made them unsuitable for use as a uniform platform.