Claims for Patent: 11,802,115

Summary for Patent: 11,802,115

Title:	Pharmaceutical formulation of odevixibat
Abstract:	The invention relates to a pharmaceutical formulation, e.g. a paediatric formulation, of odevixibat, which comprises a plurality of small particles. The formulation may be used in the treatment of liver diseases such as bile acid-dependent liver diseases, and particularly cholestatic liver diseases such as biliary atresia, progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome (ALGS) and paediatric cholestatic pruritus. The invention also relates to a process for the preparation of the pharmaceutical formulation.
Inventor(s):	Eva Byröd, Per-Göran Gillberg, Anna-Maria Tivert, Rikard Bryland, Ann-Charlotte Dahlquist, Jessica Elversson, Nils Ove Gustafsson, Robert Lundqvist, Ingvar Ymen, Martin Bohlin
Assignee:	Eva Byroed Consulting AB , Tivert Konsult AB , Albireo AB
Application Number:	US16/477,160
Patent Claims:	1. A pharmaceutical formulation of odevixibat, comprising a plurality of particles, wherein each particle is between about 0.1 and about 1.5 mm in size and comprises: a) a core, and b) a coating layer surrounding the core, wherein the coating layer comprises odevixibat or a pharmaceutically acceptable salt thereof, in an amount of from about 0.1% w/w to about 5.0% w/w based on the total weight of the particle, and a film-forming polymer; wherein each particle of the formulation substantially contains the same amount of odevixibat; and wherein the coating layer comprises odevixibat agglomerates having a d90 particle size distribution of less than 15 μm. 2. The formulation according to claim 1, wherein each particle contains odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of from about 0.5% w/w to about 2.0% w/w based on the total weight of the particle. 3. The formulation according to claim 1, wherein each particle contains odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of about 0.5% w/w based on the total weight of the particle. 4. The formulation according to claim 1, wherein each particle contains odevixibat, or a pharmaceutically acceptable salt thereof, in an amount of about 1.5% w/w based on the total weight of the particle. 5. The formulation according to claim 1, wherein the core does not contain odevixibat. 6. The formulation according to claim 1, wherein the core comprises microcrystalline cellulose. 7. The formulation according to claim 1, wherein the coating layer is prepared by spraying onto the cores a homogeneous suspension of odevixibat in water. 8. The formulation according to claim 7, wherein the homogenous suspension is prepared by dispersing odevixibat in water by wet milling. 9. The formulation according to claim 7, wherein the homogenous suspension does not contain agglomerates of odevixibat that are larger than 200 μm. 10. The formulation according to claim 1, wherein the coating layer does not contain a surfactant. 11. The formulation according to claim 1, wherein the particles are between about 0.1 and about 1.0 mm in size. 12. The formulation according to claim 1, wherein odevixibat is present as a crystalline hydrate of odevixibat. 13. The formulation according to claim 1, wherein odevixibat is present as crystal modification 1 of odevixibat. 14. The formulation according to claim 13, wherein crystal modification 1 of odevixibat has an X-ray powder diffraction (XRPD) pattern, obtained with CuKα1-radiation, with at least specific peaks at °2θ positions 5.6±0.2, 6.7±0.2 and/or 12.1±0.2. 15. The formulation according to claim 1, which is a paediatric formulation. 16. The pharmaceutical formulation of claim 1, wherein the coating layer comprises odevixibat agglomerates having a d90 particle size distribution of less than 12 μm.