Amorphous Maraviroc Solid Oral Compositions for Rapid Disintegration
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Solution Overview
Problem
Current pharmaceutical compositions of maraviroc, a CCR5 co-receptor antagonist, do not adequately address the need for improved bioavailability and patient compliance due to suboptimal disintegration and dissolution characteristics.
Innovation Solution
The development of solid oral compositions comprising maraviroc, a disintegrant, colloidal silicon dioxide as a dispersing agent, and other excipients, prepared by direct compression or dry granulation, which include specific weight ratios and particle size control of amorphous maraviroc to enhance disintegration and dissolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional pharmaceutical compositions of maraviroc are used, then the formulation is stable and manufacturable, but the disintegration and dissolution characteristics are suboptimal, leading to poor bioavailability
Solution Approach 1:
The patent changes the physical state of maraviroc from crystalline to amorphous form, which fundamentally alters the dissolution characteristics. Amorphous maraviroc lacks the ordered crystal lattice structure, resulting in higher solubility and faster dissolution rates, thereby improving bioavailability while maintaining manufacturability through direct compression or dry granulation processes
Solution Approach 2:
The patent creates a composite tablet formulation combining amorphous maraviroc with specific excipients including colloidal silicon dioxide as a dispersing agent, microcrystalline cellulose as a diluent, and magnesium stearate as a lubricant. This composite structure optimizes both the disintegration properties and manufacturability of the formulation
2Reliability
If maraviroc particle size is reduced to improve dissolution, then bioavailability increases, but manufacturing complexity increases
Solution Approach 1:
The patent specifies controlling maraviroc particle size to a d90 of not more than 150 μm, which optimizes the surface area to volume ratio for enhanced dissolution without requiring excessive size reduction that would complicate manufacturing. This particle size parameter balances dissolution rate improvement with manufacturing feasibility
Solution Approach 2:
The patent applies different quality requirements to different aspects of the formulation: amorphous state for improved dissolution, controlled particle size (d90 ≤ 150 μm) for optimal balance between dissolution and manufacturing, and specific excipient combinations for disintegration. Each parameter is locally optimized for its specific function
3Reliability
If disintegration time is reduced to improve bioavailability, then dissolution characteristics improve, but formulation stability may be compromised
Solution Approach 1:
The patent employs a carefully balanced composite formulation where amorphous maraviroc provides rapid dissolution, colloidal silicon dioxide acts as a dispersing agent to prevent agglomeration, microcrystalline cellulose provides structural stability, and magnesium stearate ensures manufacturability. This composite structure achieves disintegration time < 2 minutes while maintaining formulation stability
Solution Approach 2:
The patent specifies precise parameter ranges: amorphous maraviroc with d90 ≤ 150 μm, colloidal silicon dioxide at 0.5-5 wt%, disintegrant at 1-8 wt%, and lubricant at 0.1-2 wt%. These parameter controls ensure rapid disintegration while preventing formulation instability through proper excipient ratios
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 resulting compositions exhibit rapid disintegration and improved bioavailability, with bioequivalent performance to marketed formulations, thereby enhancing patient compliance and therapeutic efficacy.
Implementation Method 1
colloidal silicon dioxide as a dispersing agent
Data Source
AI summary
The present disclosure relates to solid dosage forms comprising the CCR5 co-receptor antagonist maraviroc. More particularly, the present disclosure relates to a solid oral dosage form containing maraviroc which has favorable disintegration properties.