Development of Novel Sustained Release Formulations for Older Adults With Swallowing Difficulties

Abstract

The older cohort is the fastest growing subsection in the population; they are the major users of medicines and are also more vulnerable to dysphagia which can make safe swallowing of solid oral dosage forms challenging. Tablets and capsules are often modified by crushing tablets or opening capsules and this can be hazardous for slow release dosage forms which reduce the pill burden for these patients but can result in dose dumping and toxicity due to modification. The aim of this study is to understand the practical issues in administering sustained release dosage forms to older adults with dysphagia and to develop novel sustained release dosage forms that are safe to swallow.

A prospective study (Chapter 2) was conducted in secondary care with the focus on administration of sustained release dosage form. There were 49% of sustained release tablets and capsules modified by crushing tablets or opening capsules to facilitate swallowing in older adults with dysphagia. Furthermore, thickened fluids, yogurt and jellies were used as vehicles to deliver modified or whole dosage forms.

Thickened fluids are commonly used to help safety of swallowing thin liquids by dysphagia patients but poorly accepted. An in vitro throat model developed for processing liquids was used to provide a systematic understanding and comparison of the flow behaviour of commonly used thickeners under simulated swallowing conditions. Slow in vitro oral transit time and cohesive bolus transit with increasing thickening was found for thickened fluids. The processing of jellies for pharmaceutical application in the throat model showed similar findings of oral transit time and bolus length to thickened fluids at high consistencies (honey and spoon thick). Rheological and textural characterisation of thickened fluids (viscosity, yield stress, firmness, cohesiveness) showed correlation with in vitro oral transit time and cohesive transit in the throat model.

Three instant (less than 10 minutes to form from powder when water was added) jellies were developed without requiring heat as a novel DIY dosage form to deliver sustained release microparticles containing gliclazide. Microparticles are useful dosage forms for patients with swallowing difficulties but can be challenging to swallow safely for patients unable to safely swallow thin liquids. The sodium alginate and calcium salts based jellies showed slow in vitro oral transit time and cohesive bolus transit in the throat model similar to commercial ready-to-eat jelly products. The jellies enhanced slow release properties of sustained release microparticles containing gliclazide suggesting that they can be effective vehicles to deliver the microparticles for patients with dysphagia.

Overall, this study showed that medicines modification does occur for sustained release dosage forms prescribed to older adults with dysphagia. Jellies showed potential as alternative swallowing aids to thickened fluids which are poorly accepted but commonly used to improve safety of swallowing of fluids by dysphagia patients. Instant jellies were developed without requiring heating with swallowing processing features similar to thickened fluids in the in vitro throat model to facilitate delivery of sustained release microparticles safely for dysphagia patients. The novel drug delivery system developed offers a promising solution for medicines administration in patients with dysphagia.