Compositions of bile acids and phenylbutyrate compounds
Inventors
Cohen, Joshua • Klee, Justin • Ma, David Wai Fung
Assignees
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Publication Number
US-11559533-B2
Publication Date
2023-01-24
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 pharmaceutical compositions and a method of preparing the composition that combine sodium phenylbutyrate with taurursodiol (TURSO) and one or more excipients to form a pre-blend. The pre-blend includes about 29.2% w/w sodium phenylbutyrate and about 9.7% w/w TURSO, and the sodium phenylbutyrate, TURSO, and excipients are blended for about 10 minutes to about 30 minutes.
The pre-blend is roller compacted using a roller compactor while maintaining the temperature at about 22°C to about 32°C using a cooling unit. The roller compactor includes two rotating rolls, a compaction force of about 5 kN/cm to about 15 kN/cm, a gap width of about 1 mm to about 5 mm, and a roll speed of about 4 rpm to about 12 rpm to produce a compacted pre-blend.
The compacted pre-blend is then granulated using a granulation screen having a diameter of about 1.5 mm to form a composition having a measurable Carr’s index of about 12 or less. The approach is directed to producing a composition with improved powder/granule flow characteristics and reduced agglomeration, reflected in measured flow metrics and subsequent performance characterization.
Claims Coverage
The document provides one independent claim directed to a method of preparing a composition, with dependent claims that further specify quantitative formulation and process parameters and measurable performance outcomes. The independent claim includes three inventive features spanning pre-blending, roller compaction under controlled temperature and roller settings, and granulation to achieve a Carr’s index threshold.
Pre-blend of sodium phenylbutyrate, TURSO, and excipients
Pre-blending sodium phenylbutyrate, taurursodiol (TURSO) and one or more excipients to form a pre-blend, wherein the pre-blend comprises about 29.2% w/w sodium phenylbutyrate and about 9.7% w/w TURSO, and the ingredients are blended for about 10 minutes to about 30 minutes.
Roller compaction under controlled temperature and roller-compactor settings
Roller compacting the pre-blend using a roller compactor while maintaining the temperature at about 22°C to about 32°C using a cooling unit, with two rotating rolls, a compaction force of about 5 kN/cm to about 15 kN/cm, a gap width of about 1 mm to about 5 mm, and a roll speed of about 4 rpm to about 12 rpm.
Granulation to achieve Carr’s index threshold
Granulating the compacted pre-blend using a granulation screen with a diameter of about 1.5 mm to form a composition having a measurable Carr’s index of about 12 or less.
Overall, the claims coverage is anchored on producing a low-Carr’s-index composition by pre-blending sodium phenylbutyrate with TURSO and excipients, roller compacting under controlled temperature and specified roller settings, and granulating to reach a measurable Carr’s index of about 12 or less.
Stated Advantages
Improves powder/granule flowability and reduces agglomeration, as characterized by Carr’s index of about 12 or less.
Provides measurable improvements in reconstitution/dissolution performance, including a reported target of about 75% release within about 0.5 to about 15 minutes.
Shows improved forced-degradation behavior, including reduced degradation under forced degradation conditions compared to TURSO.
Documented Applications
Not explicitly described in patent.
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