Ezetimibe Formulation With Controlled Particle Size for Fast Dissolution
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Solution Overview
Problem
Existing pharmaceutical compositions of ezetimibe do not achieve a fast dissolution and disintegration profile, which is crucial for effective cholesterol reduction.
Innovation Solution
A pharmaceutical composition comprising 5 to 20 wt-% ezetimibe, 50 to 85 wt-% diluent, 3 to 25 wt-% disintegrant, 2 to 5 wt-% solubility enhancer, and 1 to 10 wt-% binder, with ezetimibe having a particle size distribution of d(0.9) 9 µm to 20 µm and d(0.5) 4 µm to 10 µm, ensuring at least 90% release within 30 minutes in a specific dissolution medium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If ezetimibe is micronized to increase surface area, then dissolution rate is improved, but particle size control becomes more difficult
Solution Approach 1:
The patent applies parameter changes by precisely controlling particle size distribution parameters (d10, d50, d90) within specific ranges. This resolves the contradiction by establishing optimal particle size parameters that ensure fast dissolution while maintaining manufacturing control through defined specifications.
Solution Approach 2:
The patent employs preliminary action by pre-establishing the target particle size distribution before formulation. The specific particle size ranges are determined in advance and used as guiding parameters throughout the manufacturing process, enabling both fast dissolution and controlled production.
2Speed
If ezetimibe particle size is reduced to improve dissolution, then dissolution profile is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent resolves manufacturing complexity by defining specific particle size parameters (d10: 3-6 µm, d50: 5-8 µm, d90: 8-15 µm) that optimize dissolution while simplifying manufacturing. These parameter specifications provide clear manufacturing targets that reduce process complexity.
3Loss of time
If disintegrant amount is increased to reduce disintegration time, then disintegration is improved, but tablet hardness decreases
Solution Approach 1:
The patent applies parameter changes by optimizing the disintegrant content within a specific range (5-20 wt%) and adjusting granulation parameters. This resolves the contradiction by finding the optimal balance point where disintegration time is reduced while tablet hardness remains within acceptable limits.
Solution Approach 2:
The patent uses preliminary action by pre-establishing the optimal disintegrant content range and granulation parameters before tablet formation. This allows simultaneous optimization of both disintegration time and tablet hardness through predetermined formulation parameters.
Data Source
AI summary
The present invention relates to novel formulations comprising ezetimibe as active ingredient. In particular the invention relates to a pharmaceutical composition comprising 5 to 20 wt-% ezetimibe, 50 to 85 wt-% diluent, 3 to 25 wt-% disintegrant, 1 to 10 wt-% binder, and 0.5 to 1 wt-% lubricant, characterized in that the ezetimibe has a particle size distribution of d(0.9) of 5 µm to 35 µm and d(0.5) of 3 µm to 20 µm, as well as methods for preparing said formulations.