Apalutamide Solid Dispersion Tablets for Lower Pill Burden
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Solution Overview
Problem
Existing formulations of apalutamide for treating prostate cancer require multiple tablets per day, leading to a high pill burden and potential non-adherence issues, while maintaining bioavailability and swallowability.
Innovation Solution
Formulations comprising at least 60% w/w of a solid dispersion of apalutamide with HPMCAS or poly(meth)acrylate copolymer, allowing for a single tablet containing 240 mg of apalutamide, achieved through processes like melt-extrusion and spray-drying, with reduced excipients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If multiple tablets are used to achieve the required dose of apalutamide, then the total drug amount is sufficient, but the pill burden increases and therapy adherence decreases
Solution Approach 1:
The patent combines multiple 60mg apalutamide tablets into a single 240mg tablet formulation. This merging of multiple dosage units into one high-dose tablet directly reduces the pill burden from multiple tablets to a single tablet while maintaining the required total drug amount of 240mg, thereby improving therapy adherence
2Ease of operation
If the tablet size is increased to reduce pill burden, then fewer tablets are needed, but the swallowability and acceptance by patients deteriorates
Solution Approach 1:
The patent employs solid dispersion technology to fundamentally change the dimensional and physical state of the drug formulation. By creating a solid dispersion of apalutamide with HPMCAS or poly(meth)acrylate copolymer, the formulation achieves a compact structure that allows high drug loading (at least 60% w/w) in a single tablet while maintaining acceptable dimensions and swallowability
Solution Approach 2:
The patent changes the physical and chemical parameters of the drug formulation by using solid dispersion with specific polymers (HPMCAS or poly(meth)acrylate copolymer). This parameter change allows the formulation to achieve both high drug concentration (240mg in one tablet) and acceptable tablet size for swallowing, resolving the contradiction between reduced pill burden and maintainable swallowability
3Volume of stationary object
If the formulation contains high drug load with reduced excipients, then the tablet size can be minimized, but the manufacturing complexity increases
Solution Approach 1:
The patent utilizes solid dispersion technology which changes the physical state and distribution parameters of the drug within the formulation. This approach allows high drug load (at least 60% w/w apalutamide) with reduced excipients while maintaining manageable tablet size and simplifying the manufacturing process compared to traditional formulations that would require more complex excipient systems
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
Reduces pill burden while maintaining bioequivalence and swallowability, enhancing therapy adherence and efficiency by providing a high drug load in a single tablet.
Implementation Method 1
the solid dispersion of apalutamide and a polymer selected from HPMCAS, a poly(meth)acrylate copolymer or a mixture of HPMCAS and a poly(meth)acrylate copolymer is obtainable, in particular is obtained, by melt-extruding a mixture comprising apalutamide and a polymer selected from HPMCAS, a poly(meth)acrylate copolymer or a mixture of HPMCAS and a poly(meth)acrylate copolymer
Implementation Method 2
the solid dispersion of apalutamide and a polymer selected from HPMCAS, a poly(meth)acrylate copolymer or a mixture of HPMCAS and a poly(meth)acrylate copolymer is obtainable, in particular is obtained, by spray drying a mixture comprising apalutamide and a polymer selected from HPMCAS, a poly(meth)acrylate copolymer or a mixture of HPMCAS and a poly(meth)acrylate copolymer in a suitable solvent
Data Source
AI summary
The present invention concerns pharmaceutical formulations of apalutamide, 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.