Tebipenem pivoxil crystalline forms, compositions including the same, methods of manufacture, and methods of use
Inventors
Jain, Akash • Hecker, Evan • Edwards, Richard • Bonnaud, Thierry
Assignees
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Publication Number
US-11718621-B2
Publication Date
2023-08-08
Expiration Date
Abstract
The disclosure is directed to new crystalline tebipenem pivoxil salt forms, including a crystalline tebipenem pivoxil ethane sulfonate salt form (Form A), a crystalline tebipenem pivoxil ketoglutarate salt form (Form A), tebipenem pivoxil maleate salt forms (Form A and Form B), a tebipenem pivoxil malate salt form (Form A), a tebipenem pivoxil methane sulfonate salt form (Form B), a tebipenem pivoxil hydrobromide salt form (Form B), and a tebipenem pivoxil edisylate salt form (Form A). The disclosure also includes a composition, comprising a crystalline tebipenem pivoxil salt and a pharmaceutically acceptable carrier and further includes a method for treating an antibiotic resistant bacterial infection, comprising administering to a patient in need of such treatment a therapeutically effective amount of a crystalline tebipenem pivoxil salt.
Core Innovation
The patent discloses crystalline tebipenem pivoxil salt forms, including tebipenem pivoxil hydrobromide salt forms (Forms B/C/D), and other crystalline salt forms such as ethane sulfonate (ESA) Form A, ketoglutarate Form A, maleate Forms A and B, malate Form A, methane sulfonate (mesylate) Form B, and edisylate Form A. Each crystalline salt form is defined by an XRPD diffractogram measured using a Cu Kα source, including characteristic 2θ peak values and supported by DSC/TGA solid-state behavior and events.
The XRPD characteristic peak sets are used to identify and distinguish the crystalline salt forms of tebipenem pivoxil, with specific 2θ values and stated 2θ tolerances for the hydrobromide crystalline form. The document additionally supports the crystalline characterization with DSC profiles and TGA thermogravimetric analysis, including described thermal events such as melting/degradation behavior and other solid-state observations.
The patent further discloses pharmaceutical compositions that contain a crystalline tebipenem pivoxil salt in combination with a pharmaceutically acceptable carrier. Therapeutic use is described for treating and preventing bacterial infections, including antibiotic-resistant bacterial infections, with particular emphasis on Gram-negative infections, and the document also includes comparative/examples describing formation and interconversion between forms under storage conditions.
Claims Coverage
The provided claim set contains two independent claims directed to crystalline tebipenem pivoxil hydrobromide salt forms defined by XRPD diffractograms obtained from a Cu Kα source, including specified characteristic 2θ peak sets with stated tolerance.
XRPD-defined hydrobromide salt form by FIG. 21 peak 2θ values
A crystalline tebipenem pivoxil hydrobromide salt form wherein the XRPD of the form, obtained from a Cu Kα source, has the characteristic 2θ values of FIG. 21.
XRPD peak set hydrobromide salt form with two alternative peak sets
A crystalline tebipenem pivoxil hydrobromide salt form characterized by an XRPD diffractogram obtained from a Cu Kα source which comprises peaks at 2θ values of 12.0, 13.1, 16.3, 21.7, and 23.5±0.2 degrees 2θ; or 8.7, 9.3, 17.3, 20.8, and 22.6±0.2 degrees 2θ.
Across the independent claims, the coverage centers on crystalline tebipenem pivoxil hydrobromide salt forms identified by XRPD diffractograms measured with a Cu Kα source, using characteristic 2θ peak sets including an alternative set for the second independent claim. Dependent claims within the provided family further associate the hydrobromide form with additional solid-state characterization and pharmaceutical composition and dosage-form contexts, including Gram-negative bacterial infection uses.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating and preventing bacterial infections, including antibiotic-resistant bacterial infections, with emphasis on Gram-negative infections.
Using the disclosed crystalline tebipenem pivoxil salt forms in connection with pharmaceutical compositions and dosage forms for therapeutic use.
Documented use includes Gram negative bacterial infections including E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Neisseria gonorrhoeae, or Yersinia pestis infections.
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