Aqueous oral pharmaceutical suspension compositions
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Publication Number
US-12201639-B2
Publication Date
2025-01-21
Expiration Date
Abstract
Provided is an aqueous oral pharmaceutical suspension composition comprising vamorolone Form I. Also provided are methods for its preparation and its use.
Core Innovation
The invention describes a crystalline form of vamorolone (vamorolone Form I) characterized by an X-ray powder diffraction pattern comprising peaks at about 11.9, about 13.7, about 16.1, and about 18.3 (in terms of 2θ) with radiation Cu Kα. The crystalline form is further characterized by a thermogravimetric analysis profile showing less than about 0.5% weight loss below about 175°C.
Differential scanning calorimetry is used to define thermal events including an exothermic event onset at 180.7°C and a melting event with an onset and peak temperatures of 231.0°C and 234.7°C, respectively. The crystalline form also has chemical purity defined by impurity control, where the crystalline form has not more than 0.5% by high performance liquid chromatography of an impurity.
The invention further describes aqueous oral suspension pharmaceutical compositions containing vamorolone Form I, including formulation components such as suspending agents, suspension vehicles, surfactants, preservatives, stabilizers, buffers, and flavors. Stability statements at 25°C/60% RH indicate shelf life of at least three months, and therapeutic use is described for treating muscular dystrophy including Duchenne muscular dystrophy, and other NF-κB-mediated inflammatory diseases, by administration of the aqueous oral suspension.
Claims Coverage
The independent claim covers a crystalline form of vamorolone (vamorolone Form I) defined by four inventive features: specific pXRD peak positions, a TGA weight-loss limit below 175°C, DSC exotherm and melting temperatures, and an HPLC impurity limit of not more than 0.5%. The claim family also includes an oral pharmaceutical composition, stability at 25°C and 60% relative humidity, and therapeutic use for muscular dystrophy including Duchenne with dosing ranges.
Crystalline form characterization by pXRD with Cu Kα
A crystalline form of vamorolone characterized by an X-ray powder diffraction pattern comprising peaks at about 11.9, about 13.7, about 16.1, and about 18.3 (in terms of 2θ) with radiation Cu Kα.
TGA weight-loss limitation below 175°C
A thermogravimetric analysis profile showing less than about 0.5% weight loss below about 175°C.
DSC exotherm onset and melting onset/peak temperatures
An exothermic event onset at 180.7°C and a melting event with an onset and peak temperatures of 231.0°C and 234.7°C, respectively, as measured by differential scanning calorimetry.
HPLC impurity limitation for the crystalline form
Wherein the crystalline form has not more than 0.5% by high performance liquid chromatography of an impurity.
Oral pharmaceutical composition containing the crystalline form
An oral pharmaceutical composition that includes the crystalline form of vamorolone.
Stability at 25°C and 60% relative humidity
An oral pharmaceutical composition stable at 25°C and 60% relative humidity for at least three months.
Therapeutic treatment of Duchenne muscular dystrophy using a therapeutically effective amount
A method for treating Duchenne muscular dystrophy by administering a therapeutically effective amount.
Therapeutically effective dosing range
The therapeutically effective amount ranges from 0.01 mg/kg to 10.0 mg/kg.
The protection centers on a crystalline form of vamorolone defined by coupled solid-form and purity criteria, with additional coverage for oral pharmaceutical composition embodiments, quantified stability at 25°C/60% RH, and therapeutic use for muscular dystrophy including Duchenne with stated dosing ranges.
Stated Advantages
Provides a crystalline form of vamorolone with defined solid-form characteristics (pXRD, TGA, DSC) and controlled impurity level by HPLC (not more than 0.5%).
Provides oral pharmaceutical compositions containing the crystalline form, including stability at 25°C and 60% relative humidity for at least three months.
Documented Applications
Treating muscular dystrophy, including Duchenne muscular dystrophy, by administering the aqueous oral suspension pharmaceutical composition containing vamorolone Form I.
Treating other NF-κB-mediated inflammatory diseases by administration of the aqueous oral suspension pharmaceutical composition containing vamorolone Form I.
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