PHARMACEUTICAL GRANULATIONS OF WATER-SOLUBLE ACTIVE PHARMACEUTICAL INGREDIENTS
Granulations with granules having a high loading of an active pharmaceutical ingredient are disclosed. The active pharmaceutical ingredient has a high aqueous water solubility. The granules have a narrow particle size distribution and a smooth exterior surface.
1 . Granules comprising:
greater than 95 wt % of a compound of Formula (2a):
or a pharmaceutically acceptable salt thereof;
from 0.1 wt % to 3.0 wt % of a binder; and
from 0.1 wt % to 2.0 wt % of an antistatic agent,
wherein wt % is based on the total weight of the granules.
2 . The granules of claim 1 , wherein the granules comprise:
greater than 97 wt % of a compound of Formula (2a);
from 0.1 wt % to 1.0 wt % of a binder; and
from 0.1 wt % to 2.0 wt % of an antistatic agent,
wherein wt % is based on the total weight of the granules.
3 . The granules of claim 1 , wherein the granules comprise:
from 98 wt % to 99 wt % of the compound of Formula (2a);
from 0.25 wt % to 0.75 wt % of the binder; and
from 0.5 wt % to 1.5 wt % of the antistatic agent,
wherein wt % is based on the total weight of the granules.
4 . The granules of claim 1 , wherein the granules comprise from 97 wt % to 99 wt % of the compound of Formula (2a), wherein wt % is based on the total weight of the granules.
5 . The granules of claim 1 , wherein the granules are solid and are characterized by a substantially homogenous composition throughout the granule.
6 . The granules of claim 1 , wherein the granules are characterized by a sphericity greater than 0.90, wherein sphericity is determined using wet dispersion particle shape methods or by dynamic image analysis.
7 . The granules of claim 1 , wherein the granules are characterized by a sphericity greater than 0.95, wherein sphericity is determined using wet dispersion particle shape methods or by dynamic image analysis.
8 . The granules of claim 1 , wherein the granules have an average particle diameter (D50) less than 450 μm.
9 . The granules of claim 1 , wherein the granules are characterized by a particle size distribution (PSD) D10 from 50 μm to 150 μm, a D50 from 150 μm to 350 μm, and a D90 from 475 μm to 725 μm, wherein the particle size distribution is determined by laser diffraction or by sieve analysis.
10 . The granules of claim 1 , wherein the granules have a friability value less than 2 wt %, wherein friability is determined using a sonic sifter.
11 . The granules of claim 1 , wherein the granules a bulk density from 0.50 g/mL to 1.20 g/mL, wherein bulk density is determined according to USP 616, Method I.
12 . The granules of claim 1 , wherein the binder comprises hydroxypropyl cellulose.
13 . The granules of claim 1 , wherein the antistatic agent comprises hydrophilic fumed silica.
14 . The granules of claim 1 , wherein,
the binder comprises hydroxypropyl cellulose; and
the antistatic agent comprises hydrophilic fumed silica.
15 . The granules of claim 1 , wherein the granules comprise a coating.
16 . The granules of claim 15 , wherein the coating comprises a controlled release coating.
17 . A pharmaceutical composition comprising the granules of claim 1 .
18 . The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition comprises an oral suspension.
19 . The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition comprises an immediate release formulation.
20 . The pharmaceutical composition of claim 17 , wherein the pharmaceutical composition comprises a controlled release formulation.