Amorphous Enzalutamide Tablet Composition for Stable Dissolution
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Solution Overview
Problem
There is a need for pharmaceutical tablet compositions of enzalutamide in amorphous form that are suitable for commercial-scale production using common industry equipment and exhibit excellent long-term stability, as existing methods face challenges with scale-up and physicochemical instability.
Innovation Solution
A tablet composition comprising a granulate of enzalutamide in amorphous form and a cellulosic concentration-enhancing polymer, prepared by dissolving the components in a solvent, spraying over a substrate, and drying, followed by blending with excipients and optional coating, using standard pharmaceutical equipment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If enzalutamide is prepared in amorphous form to improve solubility and dissolution, then bioavailability is improved, but long-term stability deteriorates due to crystallization tendency
Solution Approach 1:
The patent creates a composite material system consisting of amorphous enzalutamide dispersed within a cellulosic polymer matrix (HPMCAS or HPMCP). The polymer acts as a stabilizing matrix that physically restrains the amorphous drug molecules, preventing their reorganization into crystalline structures during storage. This composite approach allows the formulation to simultaneously achieve high solubility/dissolution (from amorphous form) and long-term stability (from polymer stabilization).
Solution Approach 2:
The patent utilizes parameter changes by controlling the physical state of enzalutamide from crystalline to amorphous, and by adjusting the molecular weight and type of cellulosic polymer used. The amorphous state provides enhanced solubility and dissolution rate, while the specific polymer selection and formulation parameters ensure long-term stability by preventing crystallization during storage.
2Stability of the object's composition
If complex solid dispersion methods are used to maintain amorphous form and stability, then long-term stability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies local quality by using a specific type of cellulosic polymer (HPMCAS or HPMCP) with particular molecular weight ranges to provide localized stabilization at the molecular level within the formulation. This targeted approach using specific polymer characteristics simplifies the overall manufacturing process compared to more complex stabilization methods, as the polymer's inherent properties provide the necessary stability without requiring additional complex processing steps.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The process results in a stable, bioequivalent tablet with high density and excellent handling properties, maintaining enzalutamide in amorphous form and achieving rapid dissolution, suitable for treating castration-resistant prostate cancer.
Implementation Method 1
a cellulosic concentration-enhancing polymer, wherein said cellulosic concentration-enhancing polymer increases the solubility and dissolution rate of said amorphous enzalutamide
Implementation Method 2
Spraying the solution over the substrate; drying the obtained granulate
Data Source
Figure 1
AI summary
The present invention relates to a tablet composition comprising a granulate consisting of a co-precipitate on a substrate, wherein the co-precipitate comprises enzalutamide in amorphous form and a cellulosic concentration enhancing polymer. The invention further relates to the use of said composition as a medicament, particularly in the treatment of castration-resistant prostate cancer.