Solid pharmaceutical formulations for treating endometriosis, uterine fibroids, polycystic ovary syndrome or adenomyosis
Inventors
Qiu, Yihong • Gong, Yuchuan • RUGGLES, Alexander • Baird, Jared A. • Zu, Hui • McClelland, Gregory A. • Stepanenko, Anna V.
Assignees
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Publication Number
US-12083227-B2
Publication Date
2024-09-10
Expiration Date
Abstract
The present disclosure relates to pharmaceutical compositions comprising a gonadotropin-releasing hormone (GnRH) antagonist and methods of preparing and using such compositions. The disclosure also relates to methods of facilitating release of a GnRH antagonist from a pharmaceutical composition.
Core Innovation
The disclosure relates to solid oral pharmaceutical compositions in the form of a tablet comprising elagolix sodium. The tablet is characterized as a high drug load tablet in which the amount of elagolix sodium is about 50% to about 90% by weight of the tablet, and stability is maintained by controlling degradation of elagolix sodium within pharmaceutically acceptable levels for at least 1 month at 40° C./75% relative humidity.
The tablet uses a pharmaceutically acceptable meltable binder selected from polyethylene glycol (PEG), a cellulose derivative, a poloxamer, and combinations thereof, with an amount of about 0.1% to about 20% by weight in the broad formulation. The solid matrix is described as comprising a molecular dispersion of elagolix sodium and the pharmaceutically acceptable meltable binder.
The disclosure further describes process-related formulation architectures that enable high drug loading, including molecularly dispersed solid dispersions and multi-phase systems, and references melt-processing of elagolix sodium for tablet preparation. Optional formulation components include disintegrants, glidants, lubricants, and pH modifying agents, and the document links stability control to degradation behavior including a lactam degradation product sensitive to pH.
Claims Coverage
The independent claims cover high drug load, stable tablets comprising elagolix sodium formulated with a pharmaceutically acceptable meltable binder and defined stability control against elagolix sodium degradation under specified storage conditions. Across the independent claims, the main inventive features concentrate on high drug load composition ranges, meltable binder selection, and controlling elagolix sodium degradation for at least 1 month at 40° C./75% relative humidity, with additional composition constraints in certain independent claim variants.
High drug load and stable tablet with elagolix sodium and meltable binder
A high drug load, stable tablet comprising elagolix sodium, from about 50% to about 90% of elagolix sodium by weight of the tablet, and from about 0.1% to about 20% of a pharmaceutically acceptable meltable binder by weight of the tablet, wherein the pharmaceutically acceptable meltable binder is selected from polyethylene glycol (PEG), a cellulose derivative, a poloxamer, and combinations thereof; and controlling degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month when said tablet is stored at 40° C./75% relative humidity.
High drug load, stable tablet with defined composition ranges for binder, disintegrant, glidant, and pH modifying agent
A high drug load, stable tablet comprising from about 55% to about 60% by weight of elagolix sodium; from about 4% to about 6% by weight of a pharmaceutically acceptable meltable binder selected from polyethylene glycol 3350, hydroxypropylcellulose, poloxamer 188, and combinations thereof; from about 4% to about 6% by weight of a disintegrant; from about 0.1% to about 2% by weight of a glidant; and from about 25% to about 35% by weight of a pH modifying agent; wherein said high drug load, stable tablet controls degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month when said tablet is stored at 40° C./75% relative humidity.
High drug load, stable tablet with molecular dispersion in a solid matrix
A high drug load, stable tablet comprising elagolix sodium, from about 50% to about 90% of elagolix sodium by weight of the tablet and from about 0.1% to about 20% of a pharmaceutically acceptable meltable binder by weight of the tablet, wherein the pharmaceutically acceptable meltable binder is suitable for use in melt processing techniques for tablet preparation and wherein the tablet comprises a solid matrix, the solid matrix comprising a molecular dispersion of elagolix sodium and the pharmaceutically acceptable meltable binder; and controlling degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month when said tablet is stored at 40° C./75% relative humidity.
High drug load, stable tablet with selected disintegrant class and meltable binder
A high drug load, stable tablet comprising from about 50% to about 90% of elagolix sodium by weight of the tablet, from about 0.1% to about 20% of a pharmaceutically acceptable meltable binder by weight of the tablet, and a disintegrant selected from cross-linked modified starches, cross-linked polyvinylpyrrolidone, cross-linked carboxymethyl cellulose, and combinations thereof; wherein the high drug load, stable tablet controls degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month when said tablet is stored at 40° C./75% relative humidity.
High drug load, stable tablet comprising specified elagolix sodium amount and meltable binder selection
A high drug load, stable tablet comprising from about 55% to about 60% by weight of elagolix sodium and from about 4% to about 6% by weight of a pharmaceutically acceptable meltable binder, wherein the pharmaceutically acceptable meltable binder is selected from polyethylene glycol 3350, hydroxypropylcellulose, poloxamer 188, and combinations thereof; wherein said high drug load, stable tablet controls degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month when said tablet is stored at 40° C./75% relative humidity.
Overall, the independent claims require a high drug load tablet containing elagolix sodium with specified ranges by weight, formulated with a pharmaceutically acceptable meltable binder, and require controlling degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month at 40° C./75% relative humidity. Some independent claim variants further define a solid matrix as comprising a molecular dispersion, or specify additional component classes including disintegrant, glidant, and pH modifying agent.
Stated Advantages
Controls degradation of elagolix sodium to within pharmaceutically acceptable levels for at least 1 month when stored at 40° C./75% relative humidity.
Documented Applications
Treating endometriosis, uterine fibroids, PCOS, and adenomyosis using the non-peptide GnRH antagonist Compound A (elagolix/elagolix sodium).
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