Solid Dispersion of ARN-509 and Poly(meth)acrylate Copolymer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current pharmaceutical formulations of ARN-509 for treating androgen receptor-related diseases, particularly prostate cancer, face challenges such as limited shelf life, need for cold chain storage, and slow drug release, which can affect therapy adherence and efficiency.
Innovation Solution
The development of solid dispersions of ARN-509 combined with poly(meth)acrylate copolymers, specifically Eudragit L 100-55 and Eudragit E 100, in a weight ratio ranging from 1:1 to 1:10, which are processed through melt-extrusion or spray-drying to enhance stability, shelf life, and drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If ARN-509 is formulated in current pharmaceutical formulations, then the drug can treat androgen receptor-related diseases, but the shelf life is limited and cold chain storage is required
Solution Approach 1:
The patent changes the physical state of ARN-509 from liquid (requiring cold chain storage) to solid dispersion form, which fundamentally alters storage requirements and extends shelf life without compromising drug efficacy
Solution Approach 2:
The patent creates a composite material system by combining ARN-509 with poly(meth)acrylate copolymers to form solid dispersions, where the polymer matrix stabilizes the drug and eliminates the need for cold chain storage while extending shelf life
2Speed
If ARN-509 is formulated in current pharmaceutical formulations, then the drug can treat androgen receptor-related diseases, but the drug release is slow
Solution Approach 1:
The patent modifies the formulation parameters by creating solid dispersions with specific polymer ratios (1:1 to 1:10), which changes the drug release kinetics from slow to fast release, thereby reducing therapy time while maintaining treatment efficacy
3Ease of operation
If current pharmaceutical formulations are used, then the treatment can be administered, but the pill burden is high affecting therapy adherence
Solution Approach 1:
The patent merges multiple drug units into a single solid dispersion formulation, consolidating the required dosage into one pill that provides fast drug release, thereby reducing pill burden and improving therapy adherence without compromising treatment effectiveness
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
This formulation provides improved stability, extended shelf life, fast drug release, and reduced pill burden, thereby enhancing therapy adherence and efficiency for patients with prostate cancer.
Implementation Method 1
The solid dispersion of ARN-509 and a poly(meth)acrylate copolymer is obtainable, in particular is obtained, by melt-extruding a mixture comprising ARN-509 and a poly(meth)acrylate copolymer
Implementation Method 2
the solid dispersion of ARN-509 and a poly(meth)acrylate copolymer is obtainable, in particular is obtained, by spray drying a mixture comprising ARN-509 and a poly(meth)acrylate copolymer in a suitable solvent
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention concerns pharmaceutical formulations of ARN-509, which can be administered to a mammal, in particular a human, suffering from an androgen receptor (AR)-related disease or condition, in particular cancer, more in particular prostate cancer, including but not limited to castration-resistant prostate cancer, metastatic castration resistant prostate cancer, chemotherapy-naive metastatic castration resistant prostate cancer, biochemically relapsed hormone sensitive prostate cancer, or high-risk, non-metastatic castration-resistant prostate cancer. In one aspect, these formulations comprise a solid dispersion of ARN-509 and a poly(meth)acrylate copolymer. In one aspect, the solid dispersion of ARN-509 and a poly(meth)acrylate copolymer is obtainable, in particular is obtained, by melt-extruding a mixture comprising ARN-509 and a poly(meth)acrylate copolymer and optionally subsequently milling said melt-extruded mixture. In one aspect, the solid dispersion of ARN-509 and a poly(meth)acrylate copolymer is obtainable, in particular is obtained, by spray drying a mixture comprising ARN-509 and a poly(meth)acrylate copolymer in a suitable solvent.