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Publication Number
US-12005043-B2
Publication Date
2024-06-11
Expiration Date
Abstract
The present disclosure provides high-load tablet formulations of AG10 or a pharmaceutically acceptable salt thereof. In some aspects, provided herein are table formulations of AG10 or a pharmaceutically acceptable salt thereof that include at least 40% or more AG10 by weight and at least one pharmaceutical excipient selected from one or more fillers, one or more binders, one or more disintegrants, and one or more lubricants.
Core Innovation
The invention relates to high-load immediate-release tablet formulations comprising AG10 or a pharmaceutically acceptable salt thereof for oral delivery. The disclosure positions AG10 salts, including AG10·HCl corresponding to Formula Ia and other protic acid anion salts such as chloride, mesylate, and tosylate, as the active component and emphasizes a formulation strategy that enables tablets containing very high percentages of AG10 by weight.
A central aspect is a defined tablet composition that includes one or more fillers, one or more disintegrants, and one or more lubricants, together with specific quantitative ranges for AG10, fillers, disintegrants, and lubricants. The fillers comprise high-grade microcrystalline cellulose characterized by cellulose polymers having either spherical morphology and porous structure or needle-like particle shape, and this morphology and particle-shape definition is part of the formulation design.
The disclosure also ties the formulation to performance and quality expectations. It includes dissolution thresholds in 0.1N HCl using USP Apparatus II paddles under specified temperature and paddle speed conditions, and it reports comparative outcomes including dissolution performance, friability and stability behavior, and ageing conditions. Comparative examples and dog pharmacokinetics are described to support more consistent oral absorption associated with the AG10 tablet formulations versus certain capsule and methylcellulose-related formulations.
Claims Coverage
Two independent claims are present, each defining a high-load immediate-release tablet formulation of AG10 or a pharmaceutically acceptable salt with specified weight ranges for AG10, fillers, disintegrants, and lubricants, and requiring high-grade microcrystalline cellulose fillers characterized by spherical and porous or needle-like particle shape.
High-load immediate-release tablet with defined excipient ranges and high-grade microcrystalline cellulose morphology
A tablet formulation comprising AG10 or a pharmaceutically acceptable salt thereof and one or more fillers, one or more disintegrants, and one or more lubricants, wherein 40 to 85% by weight of AG10 or a pharmaceutically acceptable salt thereof, 5 to 55% by weight of said one or more fillers, 3 to 8% by weight of said one or more disintegrants, and 0.5 to 3% by weight of said one or more lubricants are present, and wherein said one or more fillers comprise a high-grade microcrystalline cellulose characterized by cellulose polymers with spherical morphology and porous structure or needle-like particle shape.
High-load immediate-release tablet with higher AG10 range and morphology-defined high-grade microcrystalline cellulose
A tablet formulation comprising AG10 or a pharmaceutically acceptable salt thereof and one or more fillers, one or more disintegrants, and one or more lubricants, wherein said tablet formulation comprises 50 to 75% by weight of AG10 or a pharmaceutically acceptable salt thereof, 15 to 45% by weight of said one or more fillers, 3 to 8% by weight of said one or more disintegrants, and 0.5 to 3% by weight of said one or more lubricants, and wherein said one or more fillers comprise a high-grade microcrystalline cellulose characterized by cellulose polymers with spherical morphology and porous structure or needle-like particle shape.
Across both independent claims, the claimed coverage centers on the same formulation architecture: AG10 or its pharmaceutically acceptable salt in a high percentage by weight combined with defined ranges of fillers, disintegrants, and lubricants, where the fillers are high-grade microcrystalline cellulose defined by spherical and porous morphology or needle-like particle shape.
Stated Advantages
Enables rapid dissolution performance in 0.1N HCl for the high-load AG10 tablets as compared with certain higher-loading tablets using standard microcrystalline cellulose.
Improved friability and stability behavior is described for the comparative tablet sets.
Dog pharmacokinetics are described to support more consistent oral absorption from AG10 tablet formulations versus certain capsule and methylcellulose formulations.
Documented Applications
Treating transthyretin amyloid (ATTR) cardiomyopathy by administering a tablet formulation comprising AG10 or a pharmaceutically acceptable salt thereof as defined in the relevant formulation claim.
Treating transthyretin amyloid (ATTR) polyneuropathy by administering a tablet formulation comprising AG10 or a pharmaceutically acceptable salt thereof as defined in the relevant formulation claim.
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