Apremilast Oral Dosage Forms for 24-Hour Sustained Release
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Solution Overview
Problem
Traditional oral dosage forms of apremilast do not maintain clinically relevant drug concentrations, as they release the active ingredient all at once, leading to inefficiencies and potential gastrointestinal issues.
Innovation Solution
The development of oral dosage forms comprising a core tablet with a drug layer containing apremilast and hypromellose acetate succinate in an amorphous solid dispersion, a swellable layer, and a coating layer with a drug release orifice, optimized to provide once-a-day dosing and controlled drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional rapidly disintegrating tablets are used, then the active ingredient is released all at once, but the drug concentration cannot be maintained at clinically relevant levels
Solution Approach 1:
The tablet is divided into two distinct layers: a drug layer containing apremilast and HPMCAS in amorphous solid dispersion for rapid initial release, and a swellable layer containing hydrophilic polymers (such as carbopol or hydroxypropyl cellulose) that swells to provide sustained release over 24 hours. This segmentation allows the tablet to achieve both rapid onset and prolonged duration of action.
2Ease of manufacture
If traditional tablets release all drug at once, then manufacturing is simple, but gastrointestinal symptoms occur due to high initial concentration
Solution Approach 1:
The drug release is divided into periodic phases: an initial rapid release phase from the drug layer providing immediate therapeutic effect, followed by a sustained release phase from the swellable layer that gradually releases drug over 24 hours. This periodic release pattern prevents the high initial concentration spike that causes gastrointestinal symptoms while maintaining simple tablet manufacturing processes.
3Duration of action of moving object
If a controlled release system is implemented with multiple layers, then therapeutic levels are maintained for 24 hours, but device complexity increases
Solution Approach 1:
The tablet employs composite materials to achieve controlled release without excessive complexity. The drug layer uses amorphous solid dispersion of apremilast with HPMCAS, while the swellable layer uses hydrophilic polymers such as carbopol or hydroxypropyl cellulose. These composite material choices enable 24-hour sustained release through well-understood physical mechanisms (amorphous dissolution and polymer swelling) rather than requiring complex mechanical or chemical release 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
The new dosage forms achieve sustained drug release, maintaining therapeutic levels of apremilast for 24 hours, reducing gastrointestinal discomfort and improving bioavailability.
Implementation Method 1
a drug layer comprising apremilast and hypromellose acetate succinate (HPMCAS) in an amorphous solid dispersion
Implementation Method 2
a swellable layer comprising one or more swellable polymers
Data Source
AI summary
Provided herein are oral dosage forms comprising a) a core tablet comprising (i) a drug layer comprising apremilast and hypromellose acetate succinate (HPMCAS) in an amorphous solid dispersion; and (ii) a swellable layer comprising one or more swellable polymers; and b) a coating layer disposed on the core tablet, wherein the oral dosage form surface comprises at least one drug release orifice. The disclosed oral dosage forms provide once-a-day dosing of apremilast and are suitable for treating diseases or disorders ameliorated by inhibiting phosphodiesterase subtype IV (PDE4).