US 12,337,066 B2
Controlled release granulations of water-soluble active pharmaceutical ingredients
Sami Karaborni, Cupertino, CA (US); Daniel M. Canafax, Half Moon Bay, CA (US); Jia-Ning Xiang, Fremont, CA (US); William W. Xiang, Fremont, CA (US); James Tien, Taoyuan (TW); and Nicolas D. Kirkland, Norristown, PA (US)
Assigned to XWPHARMA LTD., Grand Cayman (KY)
Filed by XWPHARMA LTD., Grand Cayman (KY)
Filed on Mar. 4, 2022, as Appl. No. 17/687,160.
Application 17/687,160 is a continuation of application No. 17/350,939, filed on Jun. 17, 2021, granted, now 11,304,906.
Claims priority of provisional application 63/059,514, filed on Jul. 31, 2020.
Claims priority of provisional application 63/040,780, filed on Jun. 18, 2020.
Prior Publication US 2022/0183977 A1, Jun. 16, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/50 (2006.01); A61K 9/16 (2006.01); A61K 31/19 (2006.01); A61K 31/225 (2006.01)
CPC A61K 9/1652 (2013.01) [A61K 9/1611 (2013.01); A61K 9/1617 (2013.01); A61K 31/19 (2013.01); A61K 31/225 (2013.01)] 21 Claims
 
1. A pharmaceutical granulation comprising a plurality of coated granules, wherein,
the coated granules comprise a core and a controlled release coating having a thickness from 5 μm to 40 μm surrounding the core, wherein 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 core comprises from 85.0 wt % to 99.5 wt % of 4-((L-valyl) oxy) butanoic acid as an active pharmaceutical ingredient having Formula (2a):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
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 pm to 500 pm, wherein the particle size distribution is determined by laser diffraction; and
the coated granules comprise from 50 wt % to 95 wt % of the compound of Formula (2a), wherein wt % is based on the total weight of the coated granules.