US 12,472,149 B2
Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form
Geoffrey De Bilde, Pont-à-Celles (BE); Pierre Sacre, Maizeret (BE); Jonathan Goole, Woluwe-Saint-Lambert (BE); Karim Amighi, Woluwe Saint-Pierre (BE); Olivier Laloux, Court-Saint-Etienne (BE); Georges Guillaume, Ophain (BE); and Vincent Stephenne, Baisy-Thy (BE)
Assigned to BE PHARBEL MANUFACTURING, Courcelles (BE)
Filed by BE PHARBEL MANUFACTURING, Courcelles (BE)
Filed on Mar. 20, 2020, as Appl. No. 16/825,873.
Application 16/825,873 is a continuation in part of application No. 15/745,190, abandoned, previously published as PCT/EP2016/066597, filed on Jul. 13, 2016.
Claims priority of application No. 15177221 (EP), filed on Jul. 17, 2015; and application No. 2016/5555 (BE), filed on Jul. 1, 2016.
Prior Publication US 2020/0315978 A1, Oct. 8, 2020
Int. Cl. A61K 9/50 (2006.01); A61K 31/426 (2006.01); A61K 9/00 (2006.01)
CPC A61K 9/5073 (2013.01) [A61K 9/5015 (2013.01); A61K 9/5026 (2013.01); A61K 31/426 (2013.01); A61K 9/0053 (2013.01)] 16 Claims
 
1. A chemically stable pharmaceutical aqueous liquid composition intended for oral administration or direct administration in the stomach comprising microparticles homogenously dispersed in an aqueous liquid medium having a pH>6, wherein said microparticles are controlled-release multilayer microparticles comprising:
a core comprising a pharmaceutically active compound, said pharmaceutically active compound being pramipexole;
a controlled-release intermediate coating layer;
an outmost external protection coating layer surrounding the controlled-release intermediate coating layer and containing a mixture of
a) a hydrophilic gastro-soluble component which is insoluble in aqueous media at a pH of between 6.5 and 7.5 and which is selected from a cationic polymer based on dimethylaminomethyl methacrylate, butyl methacrylate and methyl methacrylate, and
b) a hydrophobic and/or insoluble component which is selected from glycerides glyceryl monostearate,
wherein the weight ratio of the hydrophilic gastro-soluble component/hydrophobic and/or insoluble component is between 30/1 and 1/1, and
wherein less than 20% by weight of the pharmaceutically active compound contained in the microparticles is released in the aqueous liquid medium when the aqueous liquid composition is stored for at least one week at 25° C.