Apalutamide Crystalline Form T13 Stability Processing

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Solution Overview

Problem

Current forms of Apalutamide lack optimal solid state forms that enhance processing properties, stability, and bioavailability for effective treatment of prostate cancer, necessitating the development of new crystalline forms and salts with improved characteristics.

Innovation Solution

The development of crystalline form T13 of Apalutamide, along with processes for its preparation and pharmaceutical compositions, which include combining this form with pharmaceutically acceptable excipients for improved oral treatment formulations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing crystalline forms of Apalutamide are used, then the basic therapeutic function is achieved, but processing properties, stability, and bioavailability are not optimized

Engineering Contradiction:

ImprovestabilityVSAvoidprocessing properties

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by discovering and characterizing multiple crystalline polymorphs (Forms A through L) of Apalutamide, each with distinct physical and chemical properties. By changing the crystal structure parameters through different synthesis conditions, the patent optimizes processing properties, stability, and bioavailability while maintaining the core therapeutic function of the compound

Inventive Principle:

Principle #35Parameter changes

2Reliability

If existing crystalline forms of Apalutamide are used, then the basic therapeutic function is achieved, but bioavailability and dissolution profile are not improved

Engineering Contradiction:

ImprovebioavailabilityVSAvoiddissolution profile

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent utilizes parameter changes in crystal structure to improve bioavailability and dissolution profile. Different polymorphic forms exhibit varying solubility and dissolution characteristics, allowing selection of optimal forms for enhanced therapeutic efficacy and absorption

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite pharmaceutical compositions by combining specific crystalline forms of Apalutamide with pharmaceutically acceptable excipients. These composite formulations leverage the enhanced properties of selected polymorphs to achieve improved bioavailability and dissolution profiles

Inventive Principle:

Principle #40Composite materials

3Ease of operation

If existing crystalline forms of Apalutamide are used, then the basic formulation is achieved, but handling characteristics and storage stability are not optimized

Engineering Contradiction:

Improvehandling characteristicsVSAvoidstorage stability

Core Design Contradiction:

Ease of operationVSDuration of action of stationary object

Solution Approach 1:

The patent applies parameter changes in crystal structure to optimize handling characteristics and storage stability. Different polymorphic forms display varying mechanical properties, flow characteristics, and resistance to degradation, enabling selection of forms that facilitate manufacturing operations and ensure long-term storage stability

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP3555061B1Solid state forms of apalutamide

Publication Date: 2023.06.07 WATSON LABORATORIES INC

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AI summary

Disclosed are solid state forms of Apalutamide and salts thereof, processes for preparation thereof and pharmaceutical compositions thereof.