Compositions of bile acids and phenylbutyrate compounds
Inventors
Cohen, Joshua • Klee, Justin • Ma, David Wai Fung
Assignees
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Publication Number
US-12246027-B2
Publication Date
2025-03-11
Expiration Date
Abstract
The present disclosure relates to compositions including a phenylbutyrate compound and a bile acid, and methods of processing such compositions.
Core Innovation
The invention relates to a pharmaceutical composition comprising about 27% to about 32% w/w of sodium phenylbutyrate and about 8% to about 12% w/w of taurursodiol (TURSO), together with dextrates, sorbitol, maltodextrin, and porous silica. The sodium phenylbutyrate and the TURSO have a ratio by weight of about 3:1. The composition has a measurable Carr’s index of about 24 or less and is prepared by a method comprising dry granulation.
In the disclosed composition, the dextrates, sorbitol, and maltodextrin function together with porous silica to support powder/granule flow characteristics as indicated by Carr’s index. The formulation is associated with low Carr’s index values, including about 24 or less and a further tightened value of about 20 or less, and particle size distribution constraints are described for at least a specified fraction of particles. The composition is also described as being provided in powder or granule form within the dry granulation framework.
The disclosure further describes dry granulation processing via roller compaction to prepare a sodium phenylbutyrate/taurursodiol pre-blend followed by granulation. Characterization and formulation performance are described in terms of blend uniformity, particle size distribution, reconstitution time, and dissolution, together with measures related to agglomeration prevention and stability under forced-degradation conditions. The forced-degradation results are described as indicating reduced degradation in sachet versus APIs under some stress conditions.
Claims Coverage
The independent claim is directed to a dry-granulated pharmaceutical composition with specified weight-percent ranges for sodium phenylbutyrate, taurursodiol (TURSO), dextrates, sorbitol, maltodextrin, and porous silica, with the sodium phenylbutyrate:TURSO ratio about 3:1 and a measurable Carr’s index of about 24 or less. Inventive features across the independent and dependent claims refine formulation composition ranges and key process and solid-state performance parameters, including particle size distribution and Carr’s index thresholds, and narrow the dry granulation method to roller compaction.
Specified composition with sodium phenylbutyrate:TURSO ratio about 3:1 and Carr’s index about 24 or less
A composition comprising about 27% to about 32% w/w sodium phenylbutyrate, about 8% to about 12% w/w taurursodiol (TURSO), dextrates, sorbitol, maltodextrin, and porous silica, wherein the sodium phenylbutyrate and the TURSO have a ratio by weight of about 3:1 and wherein the composition has a measurable Carr’s index of about 24 or less.
Dry granulation preparation of the composition
The composition is prepared by a method comprising dry granulation.
Tightened sodium phenylbutyrate weight-percent range
The composition is defined as containing about 28% to about 30% w/w sodium phenylbutyrate.
Tightened TURSO weight-percent range
The claim specifies a composition further comprising about 9% to about 10% w/w of TURSO.
Particle size distribution constraint for a fraction of particles
A composition containing particles where about 45% to about 65% of the particles have a size between about 425 µm and about 1400 µm.
Lower Carr’s index performance threshold
The claimed composition has a Carr's index of about 20 or less.
Dry granulation characterized by roller compaction
The method of claim 1 is characterized in that it uses roller compaction to form the claimed composition.
Overall, the claim set centers on a dry-granulated composition containing sodium phenylbutyrate and TURSO in a weight ratio about 3:1, with specified excipient amounts, a measurable Carr’s index at or below about 24 and further tightened to about 20 or less in dependent claims, and specified particle size distribution and roller compaction in the preparation.
Stated Advantages
Improved powder/granule flowability as reflected by low measurable Carr’s index (about 24 or less, and about 20 or less in dependent claims).
Forced-degradation results described as indicating reduced degradation in sachet versus APIs under some stress conditions.
Documented Applications
The disclosed entities and context include neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, multiple sclerosis (MS), Parkinson’s disease, and Huntington’s disease.
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