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Controlled Release

IP.com Disclosure Number: IPCOM000028825D
Publication Date: 2004-Jun-03
Document File: 2 page(s) / 73K

Publishing Venue

The IP.com Prior Art Database

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CONTROLLING THE EXTENDED RELEASE PROPERTIES OF
(R)-N,N-DIISOPROPYL-3-(2-HYDROXY-5-METHYLPHYNYL)-3-PHENYLPROPANAMINE

(R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphynyl)-3-phenylpropanamine is a muscarinic receptor antagonist characterized by a relatively low water solubility. This antagonist, in its Tartrate form, is currently available in the market as capsules filled with spheres, which show extended release properties.

    Here we propose a new multi-particulate approach, in which the desired controlled release profile is achieved by the application of a bi-layered coat over water soluble (e.g. sugar/starch) cores. An additional third layer, applied as anti-tacking, protective or cosmetic coat may be included in the formulation as well. The procedure is done in two (optionally three) discrete steps using e.g. fluidized bed technology.

    The cores, which are comprised of e.g. sugar/starch spheres (pellets), in the range of 250- 1500 um, preferably 500-1100 um, comprise 50-90 % of the weight of the final formulation. These spheres are first coated with a layer containing the active ingredient or a salt thereof or a combination of these, a water soluble binder such as e.g. polyvinylpyrrolidone or hydroxypropyl methylcellulose (1-20 %, preferably 1-10 % w/w) as well as a plasticizer such as triethyl citrate or polyethylene glycol (1-10 %, preferably 1-5 % w/w). This hydrophilic first layer is then covered with the rate controlling mantle, which comprises a mixture of water insoluble polymer such as ethylcellulose (Ethocel®) and a plasticizer such as polyethylene glycol or triethyl citrate (polymer to additive ratio is preferably between 2.0 and 3.5). The rate controlling layer can be also composed of a water insoluble polymer such as polyethylacrylate-methyl methacrylate (e.g. Eudragit RL30D and/or RS30D and/or Eudragit NE30D), combined with an anti-tacking agent such as syloid, talc, or magnesium stearate (polymer to additive ratio is preferably between 1.5 and 2.5).

    The above rate controlling mantle is applied on the drug-layer coated cores in an amount of 5-35 % w/w of the final formulation, preferably, 10-25 % w/w.

    An exemplary pellet formulation has the following structure: (i...