Desmopressin oral compositions
Inventors
Tu, Yu-Hsing • Kathala, Kalyan • BHATTACHARYA, Romona • Fan, Yingjun • Perumal, Ashok
Assignees
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Publication Number
US-12214010-B2
Publication Date
2025-02-04
Expiration Date
Abstract
Provided herein are desmopressin oral liquid formulations. Also provided herein are methods of making and using desmopressin oral liquid compositions for the treatment of certain diseases including diabetes insipidus, enuresis, hemophilia A, von willebrand disease, high blood urea levels and others.
Core Innovation
The disclosure relates to a liquid pharmaceutical composition that is an oral solution comprising desmopressin acetate in an amount from about 0.01 mg/mL to about 0.1 mg/mL and water. The formulation includes a two-component, dual-functional preservative-buffer system comprising sodium benzoate and benzoic acid, which provides a pH of about 5.0. The framework links pH maintenance to storage performance and addresses instability of desmopressin acetate in oral liquid formulations.
The disclosure further describes composition refinements and performance constraints, including specified ranges for desmopressin acetate, sodium benzoate, and benzoic acid, as well as pH under defined storage conditions, impurity limits, and potency or retention after storage. The document also supports bioavailability bioequivalence relative to a reference oral tablet containing desmopressin acetate using AUC and/or Cmax.
The document provides stability study data for desmopressin-related impurities in an oral composition using HPLC impurity profiles. The data include degradation results under acid, base, oxidation, white light, and UV, pH-dependent stability across batches with pH 3.52 to 7.0, and storage stability trends measured after storage at 60°C and at 40°C/75% RH for additional batches.
Claims Coverage
The independent claim defines a ready-to-use oral liquid pharmaceutical composition with three main inventive features: a specified desmopressin acetate concentration range, a two-component dual-functional preservative-buffer system of sodium benzoate and benzoic acid providing a pH about 5.0, and the composition being an oral solution in water. The dependent claims further refine these features and add performance and quality constraints, including pH stability after storage, impurity limits measured by HPLC, and bioavailability bioequivalence to a reference oral tablet.
Low-concentration desmopressin acetate oral solution
A liquid pharmaceutical composition comprising desmopressin acetate present in an amount from about 0.01 mg/mL to about 0.1 mg/mL, wherein the liquid pharmaceutical composition is an oral solution.
Two-component dual-functional preservative-buffer system at about pH 5.0
A two-component, dual-functional, preservative-buffer system that comprises sodium benzoate and benzoic acid, wherein the two-component, dual-functional, preservative-buffer system provides a pH of the liquid pharmaceutical composition that is about 5.0.
Water-based oral solution vehicle
The liquid pharmaceutical composition further comprises water.
Across the independent claim, the core inventive concept is an oral solution containing low-concentration desmopressin acetate in water, formulated with a sodium benzoate/benzoic acid dual-functional preservative-buffer system providing a pH about 5.0. The dependent claim set adds tighter concentration ranges and post-storage quality and performance constraints, including pH stability, impurity limits measured by HPLC, and bioavailability bioequivalence to a reference oral tablet using AUC and/or Cmax.
Stated Advantages
Provides a liquid pharmaceutical composition with a pH of about 5.0 that is maintained under accelerated storage conditions.
Maintains low impurity levels, including limits on total impurities and specific desmopressin-related impurities, after storage.
Supports high desmopressin recovery (at least about 90% to about 97% wt; often at least about 95% wt) as described in the disclosure.
Achieves bioavailability bioequivalence to a reference oral tablet, based on AUC or Cmax.
Documented Applications
Accelerated storage evaluation and in-use storage in opened containers for an oral desmopressin acetate liquid pharmaceutical composition under refrigerated, ambient, and accelerated conditions, including handling of temperature excursions.
Use as an oral solution pharmaceutical composition intended to provide stability (pH maintenance and impurity control) and performance (bioavailability bioequivalence) relative to a reference oral tablet.
Forced degradation and stability study of desmopressin-related impurities in a desmopressin oral composition, using acid, base, oxidation, white light, and UV conditions with HPLC impurity profiling and mass balance.
pH-dependent stability evaluation of the oral composition across batches with pH 3.52 to 7.0, including assay and impurity outcomes after storage.
Storage stability evaluation of the oral composition at 60°C and at 40°C/75% RH for additional batches.
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