Rivaroxaban Orodispersible Tablet With Direct Compression Uniformity
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Solution Overview
Problem
Existing rivaroxaban formulations, particularly orodispersible tablets, face challenges such as lengthy manufacturing processes, high costs, variability in dissolution rates, stability issues, and difficulty in achieving bioequivalence with conventional film-coated tablets, especially when using small particle sizes that affect content uniformity and flowability.
Innovation Solution
The development of orodispersible tablets using rivaroxaban particles with a D(v, 90) less than or equal to 20.00 μm, combined with pharmaceutically acceptable disintegrants and excipients, manufactured through a direct compression process without granulation, ensuring rapid disintegration, improved stability, and adequate dissolution profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If rivaroxaban particles with small particle size (D(v, 90) ≤ 20.00 μm) are used, then dissolution rate and bioavailability are improved, but content uniformity and flowability deteriorate
Solution Approach 1:
A glidant (colloidal silicon dioxide) is introduced as an intermediary substance to improve the flowability of fine rivaroxaban particles without compromising content uniformity. The glidant reduces interparticle friction and enables smooth flow of particles with D(v, 90) ≤ 20.00 μm during direct compression manufacturing
Solution Approach 2:
The particle size distribution parameter is precisely controlled to D(v, 90) ≤ 20.00 μm to optimize dissolution rate while maintaining manufacturability. This specific particle size parameter achieves the balance between improved bioavailability and acceptable flow properties for direct compression
2Manufacturing precision
If wet granulation process is used for manufacturing orodispersible tablets, then content uniformity is improved, but manufacturing time and cost increase
Solution Approach 1:
The wet granulation steps (granulation, drying, size reduction) are completely removed from the manufacturing process. The invention achieves content uniformity through direct compression of pre-mixed powders, eliminating the time-consuming wet granulation sequence while maintaining product quality
Solution Approach 2:
Rivaroxaban particles are pre-processed to achieve the optimal D(v, 90) ≤ 20.00 μm size distribution before mixing with excipients. This preliminary particle size control enables direct compression to produce tablets with excellent content uniformity without requiring subsequent wet granulation steps
3Ease of manufacture
If conventional film-coated tablets are used, then manufacturing simplicity is maintained, but swallowing difficulty and patient compliance worsen
Solution Approach 1:
The tablet physical form is changed from conventional film-coated to orodispersible matrix structure. This parameter change in dosage form enables rapid disintegration in oral cavity (within 60 seconds) while maintaining direct compression manufacturing simplicity, thereby improving swallowing ease for elderly and pediatric patients
4Ease of operation
If orodispersible tablets with rapid disintegration are developed, then patient compliance is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The disintegration time parameter is optimized to ≤ 60 seconds through selection of specific excipients (disintegrants, binders, fillers) and their ratios. This parameter achievement enables rapid oral disintegration for patient compliance while maintaining simple direct compression manufacturing without complex processing steps
Data Source
AI summary
The present invention relates to an orodispersible tablet of rivaroxaban having overall improved characteristics. its process of manufacturing and its use as anticoagulant.