Therapeutic compounds, formulations, and uses thereof
Inventors
Alibhai, Imran • De Achaval, Sofia • LANGEVIN, Beverly C. • Zhou, Tian
Assignees
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Publication Number
US-12053444-B2
Publication Date
2024-08-06
Expiration Date
Abstract
Provided herein are compositions, formulations, and (e.g., oral) dosage forms comprising a compound of Formula (I). In specific instances, such compositions comprise an emulsifier, a solubilizer, a polyethylene glycol, a surfactant, and an antioxidant. In some instances, such compositions are useful for the treatment of fibrosis, cancer, and/or chronic inflammation.
Core Innovation
The invention relates to an improved method of administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof, to a subject in need thereof. The improvement comprises administering a pharmaceutical composition that includes the compound together with a glyceride emulsifier, a solubilizer, polyethylene glycol (PEG), a surfactant, and an antioxidant. The composition is based on a self-emulsifying-type excipient system and addresses solubility, dissolution, and stability/oxidation-related considerations associated with the compound of Formula (I).
The composition is defined by specific weight-ratio constraints relative to the compound of Formula (I). The weight ratio of the compound of Formula (I) to the glyceride emulsifier is about 1:1 to about 1:2, to the solubilizer is about 1:2 to about 1:4, to the PEG is about 1:3 to about 1:5, to the surfactant is about 1:1 to about 1:2, and to the antioxidant is about 15:1 to about 25:1. The disclosed embodiments further emphasize oral dosage forms and capsule-based formulations.
The invention further includes quantitative goals for pharmaceutical composition performance and physical characterization of a crystalline form of the compound of Formula (I) characterized by X-ray powder diffraction peak positions (2θ).
Claims Coverage
Independent claim content defines one inventive feature: an improved method of administering a compound of Formula (I) using a pharmaceutical composition with specified excipient types and weight-ratio ranges. Dependent claim content adds reduced pill burden, increased Cmax, increased AUC0→∞, specified excipient identities, and minimum amounts.
Improved method of administering compound of formula (i) via excipient-defined pharmaceutical composition
Administering to a subject in need thereof a pharmaceutical composition comprising the compound of Formula (I), or a pharmaceutically acceptable salt thereof, together with a glyceride emulsifier, a solubilizer, polyethylene glycol (PEG), a surfactant, and an antioxidant, wherein the weight ratios relative to the compound of Formula (I) are about 1:1 to about 1:2 for the glyceride emulsifier, about 1:2 to about 1:4 for the solubilizer, about 1:3 to about 1:5 for the PEG, about 1:1 to about 1:2 for the surfactant, and about 15:1 to about 25:1 for the antioxidant.
Reduced pill burden relative to a specified comparator
Providing that the improvement reduces pill burden by at least 2-fold than when a pharmaceutical composition consisting essentially of the compound of Formula (I), a glyceride emulsifier, and PEG are administered in a glyceride emulsifier:PEG weight ratio of about 60:40.
Increased cmax relative to the specified comparator
Providing a Cmax that is at least 1.3 times greater than when a pharmaceutical composition consisting essentially of the compound of Formula (I), a glyceride emulsifier, and PEG are administered in a glyceride emulsifier:PEG weight ratio of about 60:40.
Increased auc0→∞ relative to the specified comparator
Providing that the AUC 0→∞ is at least 1.3 times greater than that obtained when administering a pharmaceutical composition consisting essentially of the compound of Formula (I), a glyceride emulsifier, and PEG in a weight ratio of about 60:40.
Minimum amounts of excipients and antioxidant
Containing at least 50 mg of the glyceride emulsifier, at least 100 mg of the solubilizer, at least 150 mg PEG, at least 50 mg of surfactant, and at least 2 mg of the antioxidant.
Polyoxyl castor oil as the solubilizer
Carrying out the method using polyoxyl castor oil as the solubilizer.
Overall, the claims coverage centers on administering the compound of Formula (I) in a pharmaceutical composition defined by specific excipient categories and weight-ratio ranges, with dependent refinements that quantify improvements in pill burden, Cmax, and AUC0→∞ versus a comparator formulation having a glyceride emulsifier:PEG weight ratio of about 60:40, and further specify certain excipient identities and minimum component amounts.
Stated Advantages
Improves pill burden by at least 2-fold compared with a comparator composition with a glyceride emulsifier:PEG weight ratio of about 60:40.
Provides a Cmax at least 1.3 times greater than the comparator composition with a glyceride emulsifier:PEG weight ratio of about 60:40.
Provides an AUC0→∞ at least 1.3 times greater than that obtained with the comparator composition with a glyceride emulsifier:PEG weight ratio of about 60:40.
Documented Applications
Treating cancer.
Treating fibrosis.
Treating chronic inflammation.
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