Controlled release granulations of water-soluble active pharmaceutical ingredients

A pharmaceutical granulation for once a day dosing comprising a plurality of coated granules, wherein,

• the coated granules comprise a core and a controlled release coating surrounding the core;
• the core comprises from 90.0 wt % to 99.5 wt % of a compound of Formula (2):
• or a pharmaceutically acceptable salt thereof, wherein,
• R1 is selected from hydrogen and C1-6 alkyl;
• and
• each of R2 and R3 is independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxycarbonyl, and C3-6 cycloalkoxycarbonyl;
• wherein wt % is based on the total weight of the core;
• the coated granules are characterized by a particle size distribution (PSD) (D50) from 150 μm to 500 μm, wherein the particle size distribution is determined by laser diffraction;
• the coated granules comprise from 50 wt % to 95 wt % of the compound of Formula (2), wherein wt% is based on the total weight of the coated granules;
• the controlled release coating comprises:
• from 60 wt % to 85 wt % of a matrix polymer, wherein the matrix polymer comprises:
• from 92 wt % to 98 wt % of a water-insoluble polymer;
• and
• from 2 wt % to 8 wt % of a water-soluble polymer,
• wherein wt % is based on the total weight of the matrix polymer;
• from 10 wt % to 20 wt % of talc;
• and
• from 3 wt % to 13 wt % of dibutyl sebacate,
• wherein wt % is based on the total weight of the controlled release coating;
• and
• the controlled release coating has a thickness from 5 μm to 40 μm.