Solid dosage form having excellent stability
Inventors
MIZUTANI, Naoya • Morimoto, Masayuki • OKABE, MAKI • Ito, Masaaki • KIMURA, Go
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12427156-B2
Publication Date
2025-09-30
Expiration Date
Abstract
The present invention provides a solid dosage form having good stability, suspensibility in water and fluidity by preparing a solid dosage form containing a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, a stabilizer, a sugar alcohol and/or a sugar, a water-soluble polymer and an inorganic substance.
Core Innovation
The invention relates to a solid dosage form containing a polycyclic pyridone prodrug represented by formula (I) for influenza, wherein the solid dosage form is in the form of a granule. The granule comprises maltitol and mannitol and one or more substances selected from an organic acid, a polyhydric alcohol ester, a fatty acid ester, and a water-soluble polymer, and further comprises specific excipient components including alkali metal chloride and inorganic agents as described in the partial content.
The formulation addresses temporal stability by reducing an increase of related substance (compound represented by formula (II)) during temporal storage. In addition, the solid dosage form is formulated to improve water suspensibility, container adherence, fine granule yield, fluidity, and dissolution or release rate, including the release performance after storage as described in the partial content.
The partial content also describes constraints regarding the placement of excipients, including that the polymer and inorganic agents are absent from coating layers. Comparative examples within the partial content support that selected stabilizers and suspending-agent combinations reduce the increase of related substance and improve suspensibility, while maintaining release rate after storage.
Claims Coverage
The independent claim covers a solid dosage form in the form of a granule comprising a compound represented by formula (I), with maltitol and mannitol, plus selected excipients from an organic acid, a polyhydric alcohol ester, a fatty acid ester, and/or a water-soluble polymer. Dependent claims further narrow excipient selections and structural constraints, including an absence of a coating layer.
Granule solid dosage form with maltitol and mannitol plus selected excipients
A solid dosage form is in the form of a granule comprising a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, maltitol, mannitol, and one or more substances selected from an organic acid, a polyhydric alcohol ester, a fatty acid ester and a water-soluble polymer.
Organic acid selection
The solid dosage form comprises an organic acid selected from ascorbic acid and fumaric acid.
Polyhydric alcohol ester selection
The solid dosage form comprises a polyhydric alcohol ester selected from Miglyol, triethyl citrate, and polyoxyethylene sorbitan monooleate.
Fatty acid ester selection
The solid dosage form comprises a fatty acid ester specifically triacetin.
Absence of coating layer
The solid dosage form is defined such that it does not include a coating layer.
Across the independent claim, the core inventive structure is a granule-based solid dosage form for a polycyclic pyridone prodrug of formula (I) comprising maltitol and mannitol plus selected stabilizing and excipient classes, with dependent features specifying particular excipients and excluding a coating layer.
Stated Advantages
Reduced increase of related substance (compound represented by formula (II)) during temporal storage.
Improved water suspensibility.
Improved container adherence.
Improved fine granule yield.
Improved fluidity (angle of repose).
Dissolution/release rate maintained, including achieving 80% or more at 15 min.
Documented Applications
A solid dosage form for influenza using a polycyclic pyridone prodrug represented by formula (I) formulated as granules.
Interested in licensing this patent?