Abstract

Gastro-retentive drug delivery systems (GRDDS) can improve the erratic drug absorption of certain drugs, for example, theophylline. The formulation design of floating pellets is of a particular interest, due to the minimised risk of complete emptying into the intestine and the minimised gastro-intestinal tract (GIT) irritation. Core pellets are usually prepared by extrusion and spheronisation (E/S) processes, and are usually coated with more than one film before capsule filling or tableting processes. This research increased the understanding in the pharmaceutical floating pellets systems. The main aim of this research study was to develop novel gastro-retentive floating pellets, using the E/S processes with a new spheronisation aid not used before (Avicel HFE 102; co-processed microcrystalline cellulose with ~10% mannitol) and the use of 10% ethanol as a liquid binder for obtaining high sphericity (target: Aspect ratio; AR <1.2). Avicel HFE 102 was also used as a cushioning aid in the form of powder or pellets, to allow the compression of coated pellets into tablets whilst maintaining sufficiently sustained drug release and floating properties. In addition, the use of a single and thin film coat (made by Eudragit NE15 diluted by 25% ethanol) was studied to produce pellets with properties of sustained drug release (preferable target: 12-24 hours) and floating (preferable target: 6-12 hours, >90% floated, <15 minutes lag time). Mainly, the size and shape analysis of the core pellets was determined. The drug release and floating properties of the coated pellets were determined. The core pellets studies prior the enhancement of the single-coating (where the 10% ethanol was used as a liquid binder) showed that they exhibited spherical shape AR<1.2. In either 0.1N HCl medium or distilled water medium, the enhanced and novel single-coated floating pellets (where the film made by the Eudragit NE15 dispersion -diluted with 100% ethanol, to obtain 25 w/w% ethanol containing dispersion-) showed that they exhibited drug release for 24 hours or more. And, >98% of the latter pellets floated on surface, for at least 12 hours, with a lag time of 10-15 minutes. After which, the enhanced single-coated pellets were
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compressed along with the cushioning powder. Upon tablets disintegration in 0.1N HCl medium, the single-coated floating pellets showed sustained drug release for up to 8 hours or more, and the floating was at least for 24 hours. That is, the compression of the enhanced single-coated pellets into tablets still produced useful pellets. To sum the main points, core pellets were successfully made regarding shape properties, using the new spheronisation aid (Avicel HFE102). And, the single-coated floating pellets were successfully made and intensively investigated for properties, like shape, drug release, and floating properties. The success of the latter pellets is mainly attributed to the use of ethanol in the liquid binder and the coating dispersion, respective to the enhanced core pellets and the enhanced single-coated pellets. The spherical core pellets and the single thin layer of only ~6.5% weight gain were obtained. The latter coating layer had the enhanced floating and sustained drug release properties.