Formulation of a pan-JAK inhibitor
Inventors
Nitert, Bernardus Joseph • Rosiaux, Yvonne • Van Der Veen, Marian E. • Schulpen, Nathan • Maes, Jens • Verniest, Guido • Thalladi, Venkat R. • Ching, Ai Ling
Assignees
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Publication Number
US-11795180-B2
Publication Date
2023-10-24
Expiration Date
Abstract
The present disclosure relates to pharmaceutical compositions comprising (3-((1R,3s,5S)-3-((7-((5-methyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propanenitrile), methods of use thereof, and methods of preparation.
Core Innovation
The invention is an oral immediate-release pharmaceutical composition comprising Compound I, a pan-JAK inhibitor, or a pharmaceutically acceptable salt thereof, combined with microcrystalline cellulose, lactose, hydrophobic silicon dioxide, magnesium stearate, and low-substituted hydroxypropyl cellulose. The composition optionally comprises a coating and is presented as a tablet formulation. The formulation provides rapid and consistent dissolution while maintaining low chemical degradation.
The composition addresses sticking during tableting and prevents punch filming through the incorporation of hydrophobic silicon dioxide. Formulations pre-blended with hydrophobic colloidal silicon dioxide demonstrate improved dissolution and minimal impurity formation compared to alternative blending approaches. Additionally, low-substituted hydroxypropyl cellulose provides a favorable degradation profile comparable to the active ingredient alone without causing discoloration.
Claims Coverage
The claims identify one independent claim and one main inventive feature directed to a pharmaceutical composition containing Compound I and specified excipients.
Pharmaceutical composition containing Compound I and specified excipients
The independent claim covers a pharmaceutical composition comprising Compound I or a pharmaceutically acceptable salt thereof; microcrystalline cellulose; lactose; hydrophobic silicon dioxide; magnesium stearate; and low-substituted hydroxypropyl cellulose (L-HPC), with an optional coating.
The independent claim defines the pharmaceutical composition with the specified excipients, while dependent claims further refine ingredient proportions, material properties, crystalline form, coating, dosage and dosage form, impurity limitations, preparation, and therapeutic use for gastrointestinal inflammatory disease.
Stated Advantages
The formulation addresses sticking during tableting and avoids punch filming.
The formulation supports rapid and consistent dissolution, reporting complete dissolution within 45 minutes and retention of fast dissolution across fine, intermediate, and coarse API particle sizes.
The formulation shows reduced degradation and low degradation during stability testing, with minimal impurity formation when formulated with hydrophobic colloidal silicon dioxide.
L-HPC exhibits a degradation profile comparable to Compound I alone without discoloration.
Pre-blending Compound I with hydrophobic colloidal silicon dioxide improves dissolution compared with blending it with filler and lubricant.
Documented Applications
The composition is described for treating gastrointestinal inflammatory disease, including ulcerative colitis and Crohn's disease, in a mammal in need thereof.
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