Amorphous Enzalutamide Solid Dispersion for Single-Tablet Absorption

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Solution Overview

Problem

Existing formulations of enzalutamide, an androgen receptor signaling inhibitor, face challenges in achieving suitable solubility, dissolution stability, and absorption, making it difficult to develop a single tablet alternative to soft capsules for treating castration-resistant prostate cancer.

Innovation Solution

A solid dispersion of amorphous enzalutamide with hydroxypropyl methylcellulose acetate succinate as a concentration-enhancing polymer, combined with mixing and granulating processes, to enhance solubility and absorption, allowing for a single tablet dosage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If enzalutamide is formulated as a soft capsule, then solubility and absorption are improved, but device complexity and manufacturing difficulty increase

Engineering Contradiction:

Improvesolubility and absorptionVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent transforms enzalutamide from crystalline to amorphous form, fundamentally changing its physical state and dissolution properties. This parameter change enables the drug to achieve enhanced solubility and absorption in a simpler tablet formulation without requiring soft capsule delivery systems

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material by combining amorphous enzalutamide with specific polymers (hydroxypropyl methylcellulose acetate succinate and/or polyvinylpyrrolidone) in a solid dispersion. This composite structure maintains the solubility-enhancing properties while enabling simpler tablet formulation

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If polymers are added to improve solubility, then aqueous concentration may increase, but dissolution stability and prediction of drug-polymer interaction become difficult

Engineering Contradiction:

Improveaqueous concentrationVSAvoiddissolution stability

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent specifies precise parameter ranges for polymer content (0.5 to 7 parts by weight per part of enzalutamide) and drug loading (20-75 wt%) to optimize the balance between aqueous concentration enhancement and dissolution stability. These controlled parameter changes make the system predictable and manufacturable

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses hydroxypropyl methylcellulose acetate succinate and polyvinylpyrrolidone as intermediary substances that mediate between the amorphous enzalutamide and the aqueous environment. These polymers provide predictable interactions that enhance solubility while maintaining dissolution stability

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If amorphous enzalutamide is used to improve dissolution, then solubility increases, but maintaining amorphous state stability becomes challenging

Engineering Contradiction:

Improvesolubility and dissolutionVSAvoidamorphous state stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent stabilizes the amorphous state by incorporating it into a polymeric matrix, creating a composite material where the polymer network restrains molecular reorganization that would lead to crystallization. This composite structure maintains amorphous stability while preserving enhanced solubility

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent creates local amorphous regions dispersed within the polymeric matrix, where the immediate molecular environment prevents crystallization. This local quality approach stabilizes the amorphous state without requiring the entire formulation to be amorphous

Inventive Principle:

Principle #3Local quality

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 formulation provides rapid disintegration, improved solubility, and enhanced oral bioavailability, enabling a single daily dose of enzalutamide with increased aqueous concentration and stability, suitable for treating hyperproliferative disorders like prostate cancer.

Implementation Method 1

a solid dispersion of amorphous enzalutamide with hydroxypropyl methylcellulose acetate succinate

Methodology Applied

Scientific EffectSolid dispersion:

Implementation Method 2

amorphous enzalutamide

Methodology Applied

Scientific EffectAmorphous form:

Implementation Method 3

rapid disintegration

Methodology Applied

Scientific EffectDisintegration:

Implementation Method 4

improved solubility

Methodology Applied

Scientific EffectDissolution:

Data Source

PatentEP3725778B2Formulations of enzalutamide

Publication Date: 2026.01.07 MEDIVATION PROSTATE THERAPEUTICS LLC

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Figure 2A~2B
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AI summary

This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.