Pharmaceutical compositions
AssigneeGenzyme Corporation
InventorsStephen Randall Holmes-Farley, David J. Harris, Steven C. Polomoscanik, Adnan Salameh, Bruce Shutts, Richard Silva, Pradeep K. Dhal, Lynne Sole
Life of this patent
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Abstract
The present invention relates to crosslinked polyamine particles and/or pharmaceutical compositions comprising, at least in part, crosslinked polyamine particles and aggregates of such particles (including cured aggregates of crosslinked polyamine particles). The compositions may be in the form of tablets comprising, for example, particles larger than 500 μm, and used for treating patients, for example, patients with hyperphosphatemia.
Claims39
A pharmaceutical composition comprising a crosslinked amine polymer comprising:
- i) repeat units represented by the following Formula I and/or Formula II:
- wherein m is an integer from 0 to 2;
- n is an integer and each R1, R2 and R3 independently represent hydrogen;
- substituted or unsubstituted, branched or unbranched C1-C6 alkyl;
- substituted or unsubstituted, branched or unbranched C1-C6 alkylamino;
- X− is a pharmaceutically acceptable counterion;
- and
- ii) a crosslinking agent or residue thereof;
- wherein said crosslinked amine polymer comprises particles having a dry particle size distribution wherein greater than 10 vol. % of the particles have a particle size larger than 500 μm.
A method of manufacturing a pharmaceutical composition comprising:
- forming constituent particles having a d50 between 70 μm and 150 μm comprising polyallylamine crosslinked with 8-11 wt. % epichlorohydrin, or a pharmaceutically acceptable salt thereof;
- suspending said particles in a solvent;
- drying the suspended particles;
- and
- fractionating the dried particles to obtain crosslinked amine polymer particles wherein greater than 10 vol. % of the particles have a particle size larger than 500 μm.
A method of manufacturing a pharmaceutical composition comprising:
- a) neutralizing or partially neutralizing polyallylamine hydrochloride;
- b) crosslinking said polyallylamine hydrochloride with 8-11 wt. % epichlorohydrin;
- c) forming constituent particles of crosslinked polyallylamine hydrochloride, having a particle size d50 value of between 50 μm and 400 μm by wet milling;
- d) carbonating said washed and/or neutralized particles;
- e) drying said carbonated particles;
- f) hydrating said carbonated particles;
- g) re-drying said carbonated particles;
- and
- h) grinding and/or sieving said re-dried particles to form crosslinked amine polymer particles having a d50 value of between 675 μm and 1000 μm.
Dependencies are inferred from the claim text.