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Factors influencing the release profile from a multiparticulate delivery system

IP.com Disclosure Number: IPCOM000011953D
Publication Date: 2003-Mar-27
Document File: 2 page(s) / 91K

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Factors influencing the release profile of(±) 1-(isopropylamino)-3-[p-(β-methoxyethyl) phenoxy]-2-propanol succinate (2:1 salt) from a multiparticulate delivery system

A multiparticulate sustained release formulation of (±) 1-(isopropylamino)-3-[p-(β-methoxyethyl) phenoxy]-2-propanol succinate (2:1salt) was developed.

The formulation consists of a sustained release coated core pellets, which eventualy can be compressed into tablets. This multiparticulate delivery system was manufactured in three discrete steps. Firstly, a core comprising the active (±) 1-(isopropylamino)-3-[p-(β-methoxyethyl) phenoxy]-2-propanol succinate (2:1salt) and other pharmaceutical excipients was designed. The latter, comprise mainly about 20-60% (w/w) of insoluble components (microcristalline cellulose, starch) and about 10-45% (w/w) of soluble components (lactose), preferably, 25- 45% w/w insoluble components and 15-35% w/w of soluble components.

The core pellets were prepared by using extrusion/spheronization technology. Accordingly, the dry components were blended together and moisturized with appropriate amount of water or hydroalcoholic solution in order to produce a plastic, extrudable mass. This mass was extruded and transformed into spheres by the aid of a spheronizer. After drying, these spheres provided thecore pellet substrate for furthersustained release coating. The parameters affecting the release profile of the final dosage form, which can be modulated in this step are the sphericity , size and porosity of the core pellets. By altering the process parameters, such as the extruder screen, spheronization speed, or the moisturizing solution type, (water versus hydroalcoholic solution) different sizes, shapes and densities of core pellets can be obtained.

It is known to those skilled in the art that the amount of soluble ingredient in the pellet core, strongly influences the release profile, due to osmotic pressure built up within the coated pellet. However, in the case described in this paper, varying the soluble ingredient amount within the range of 10-45% w/w did not significantly alter the drug release.

The next step in the manufacturing of the sustained release formulation is the application of a rate controlling "mantle" (or coating). This coating can be applied by means of the coating techniques known in the state of the art, such as Fluid bed coating technologies (top, bottom spray and rotor techniques). The rate controlling mantle comprises pharmaceutically compatible polymers, such as poly(ethylacrylate- methylmethacrylate)(Eudragit NE), or polyvinylacetate ( Kollicoat SR), or ethocel aqueous dispersion ( Surelease), or ethocel organic...