Formulations of deferasirox and methods of making the same
Inventors
Miller, Dave A. • Keen, Justin M. • KUCERA, Sandra U.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10265301-B2
Publication Date
2019-04-23
Expiration Date
Abstract
The disclosure provides for improved pharmaceutical compositions containing deferasirox (DFX) and methods of manufacturing the same. In particular, the compositions are prepared using thermokinetic compounding and provide improved properties as well as more efficient methods of manufacture.
Core Innovation
The invention relates to improved deferasirox (DFX) amorphous solid dispersions formulated to form melt-blended pharmaceutical composites using thermokinetic compounding (TKC) and KinetiSol 4. The compositions include DFX and one or more pharmaceutically acceptable excipients and are described as having an amorphous morphology with a single glass transition temperature. The objective is to maintain the amorphous morphology while enabling high DFX loading and limiting thermal degradation during formation.
The background problem addressed is that DFX is used in iron chelation for chronic iron overload and in β-thalassemia, and the formulation needs improved performance while controlling stability-related degradation. The disclosed compositions are characterized to retain XRD-amorphous morphology during storage and to limit degradation products. The formulation is further described by DFX drug loading, DFX purity, and constraints on degradation products, along with characterization by XRD and modulated differential scanning calorimetry (mDSC) to evidence the single Tg behavior.
The invention also emphasizes performance attributes including dissolution and oral pharmacokinetics (PK), including enhanced oral exposure (AUC) versus crystalline/marketed references with reduced variability and reduced/limited food effect. The compositions are linked to peak solubility in a defined aqueous buffer pH range (pH 4–8) and dissolution improvements. Examples include oral dosage forms such as capsules and tablets with differing disintegrating versus eroding designs, with comparisons described against Jadenu 4 and Exjade 4 in dog and human studies.
Claims Coverage
Based on the provided independent claim, the core inventive subject matter is a DFX amorphous solid dispersion with a single glass transition temperature. Dependent claims add quantitative and compositional limitations including degradation products, purity, optional absence of processing agents and/or plasticizers, and a solubility threshold, and narrow the composition into oral dosage form categories.
Pharmaceutical composition with an amorphous solid dispersion and a single glass transition temperature
A pharmaceutical composition comprising an amorphous solid dispersion of deferasirox (DFX) and one or more pharmaceutically acceptable excipients, wherein said composition has a single glass transition temperature.
Less than about 1.0% degradation products of DFX
The composition contains deferasirox (DFX) with less than about 1.0% degradation products of DFX.
Specified DFX purity
The purity of DFX used in said composition is about 95%, about 99%, about 99.5%, or within a range of about 95% to about 100%.
Peak solubility exceeding 400 μg/mL at pH 4–8
The peak solubility of DFX in the composition exceeds 400 μg/mL when measured in an aqueous buffer with a pH between 4 and 8.
Absence of processing agent and/or plasticizer
The composition lacks a processing agent and and/or lacks a plasticizer.
Oral dosage form selected from a tablet, capsule, or sachet
The pharmaceutical composition is provided as an oral dosage form selected from a tablet, a capsule, or a sachet.
The claims cover DFX amorphous solid dispersions that exhibit a single glass transition temperature, with dependent limitations focused on controlled degradation products, defined DFX purity, a peak solubility threshold in a pH 4–8 buffer, optional absence of processing agents and/or plasticizers, and specific oral dosage form categories.
Stated Advantages
Improved oral exposure (AUC) versus crystalline/marketed references with reduced variability.
Reduced/limited food effect.
Retention of XRD-amorphous morphology during storage.
Dissolution improvements and enhanced peak solubility in a defined pH range (pH 4–8).
Documented Applications
Iron chelation in chronic iron overload.
β-thalassemia.
Oral dosage form administration in capsules and tablets, with described disintegrating versus eroding design comparisons.
Comparative dog and human studies against Jadenu 4 and Exjade 4.
Interested in licensing this patent?