Bempedoic Acid Granulation for Flowability
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Solution Overview
Problem
Bempedoic acid and Ezetimibe, both BCS Class II compounds, face challenges due to poor water solubility and stickiness, leading to difficulties in pharmaceutical formulation, including poor flow characteristics and stability issues, which affect tablet compression and drug manufacturing processes.
Innovation Solution
Development of novel combination formulations involving surface treatment of Bempedoic acid with colloidal silicon dioxide and blending with hydroxypropyl cellulose and microcrystalline cellulose, along with a binder solution, to improve flowability and stability, resulting in monolayer and bilayer tablet formulations with enhanced bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Bempedoic acid is used in pharmaceutical formulation, then the drug provides therapeutic effect, but it exhibits poor flow characteristics and stickiness that adversely impact manufacturing processes
Solution Approach 1:
The patent uses colloidal silicon dioxide as an intermediary substance to treat Bempedoic acid particles. This mediator reduces the stickiness and improves flow characteristics by creating a coating on the drug particles, allowing them to interact more favorably with other formulation components during manufacturing processes.
Solution Approach 2:
The patent changes the physical parameters of Bempedoic acid by treating it with colloidal silicon dioxide and undergoing granulation processes. These parameter changes include modifications to surface properties, particle size distribution, and bulk density, which collectively improve flow characteristics while maintaining therapeutic efficacy.
2Reliability
If Bempedoic acid is used in pharmaceutical formulation, then the drug provides therapeutic effect, but it exhibits stickiness that adversely impacts tablet compression operations
Solution Approach 1:
The patent converts the harmful stickiness property of Bempedoic acid into a beneficial characteristic by using it as a binding agent during granulation. The stickiness that causes manufacturing problems is harnessed to promote particle aggregation and formation of granules with improved flow and compression properties.
Solution Approach 2:
The patent employs colloidal silicon dioxide as an intermediary to modify the surface properties of Bempedoic acid, reducing excessive stickiness that causes manufacturing issues while preserving the drug's therapeutic properties and controlled release characteristics.
3Ease of manufacture
If standard granulation is applied to Bempedoic acid, then some improvement in processability is achieved, but the stickiness is only marginally reduced
Solution Approach 1:
The patent applies preliminary surface treatment with colloidal silicon dioxide before the granulation process. This preliminary action modifies the surface properties of Bempedoic acid particles, making them less sticky and more amenable to subsequent granulation and compression operations, thereby achieving better processability than standard granulation alone.
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 formulations achieve improved pharmacokinetic and bulk physical properties, reducing stickiness and enhancing dissolution profiles, thereby improving the manufacturing and efficacy of Bempedoic acid and Ezetimibe pharmaceutical compositions.
Implementation Method 1
surface treatment of ETC-1002 with colloidal silicon dioxide reduces or eliminates the stickiness problem
Implementation Method 2
mixing the blend with hydroxypropyl cellulose (HPC-L) and microcrystalline cellulose in rapid mixer granulator
Data Source
AI summary
Herein disclosed are novel compositions comprising: Bempedoic acid and Bempedoic acid and Ezetimibe, kits, methods of using and processes for making said novel compositions. Notably, the formulations herein provide pharmaceutical compositions having excellent stability and release properties for both drug products. These improved formulations are useful in the treatment and prevention of cardiovascular disease.