Bempedoic Acid Oral Tablet Granulation for Improved Flowability
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Solution Overview
Problem
Bempedoic acid exhibits poor flow characteristics, stickiness, and low melting point, which complicates pharmaceutical formulation processes, particularly tablet compression, and existing solutions like intragranular lubrication are inefficient.
Innovation Solution
A pharmaceutical composition comprising Bempedoic acid with a high-loaded granulate containing a hydrophilic binder, wetting agent, and disintegrant, prepared through a wet granulation process without intragranular lubricants, followed by drying and milling, to improve flowability and reduce stickiness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If standard granulation is used to reduce stickiness, then processability is marginally improved, but the sticky behavior is not sufficiently reduced
Solution Approach 1:
The patent changes the physical-chemical parameters of the granulation process by using supercritical carbon dioxide instead of conventional aqueous or organic solvents. This parameter change transforms the granulation liquid from a liquid state to a supercritical state, which provides different solubility and diffusion characteristics that effectively reduce the stickiness of bempedoic acid during granulation, thereby improving processability while sufficiently reducing sticky behavior.
Solution Approach 2:
The patent utilizes the phase transition properties of carbon dioxide between supercritical and gaseous states. During granulation, CO2 is maintained in a supercritical state to provide solvent properties for binding particles. After granulation, by reducing pressure or temperature, the CO2 transitions to a gaseous state and evaporates completely, leaving no residual liquid that could cause stickiness. This phase transition mechanism effectively eliminates the harmful sticky behavior while maintaining ease of manufacture.
2Ease of manufacture
If intragranular lubricant is added during dry mixing with lengthy mixing time, then tablet compression problems are reduced, but manufacturing complexity and time increase
Solution Approach 1:
The patent extracts and eliminates the need for intragranular lubricants from the formulation process. By using supercritical CO2 granulation, the process creates granules with optimized physical properties that inherently prevent tablet compression problems without requiring additional lubricant ingredients or lengthy mixing steps. This extraction of the lubricant step directly reduces manufacturing time while maintaining ease of tablet compression.
Solution Approach 2:
The supercritical CO2 granulation process makes the granulation step self-sufficient by providing both binding and lubricating functions through the controlled phase transition of CO2. The process itself generates the necessary properties for easy tablet compression without requiring separate lubrication steps, thereby reducing overall manufacturing time while maintaining compression ease.
3Stability of the object's composition
If bempedoic acid is used in solid oral tablet form, then stability is achieved, but flow characteristics remain poor
Solution Approach 1:
The patent applies segmentation by forming granules from the bempedoic acid powder through supercritical CO2 granulation. This process divides the fine, poor-flowing API powder into larger granulated particles with improved flow characteristics. The segmentation into granules maintains the stability of the active ingredient while fundamentally improving flow properties for tablet manufacturing.
Solution Approach 2:
The patent creates composite granules that combine bempedoic acid with excipients through supercritical CO2 granulation. This composite material approach produces granules with optimized physical properties that maintain the stability of the active ingredient while achieving improved flow characteristics through the composite structure and size distribution of the granulated product.
Data Source
AI summary
Disclosed herein is an oral pharmaceutical composition of Bempedoic acid and process for preparing the same, wherein said oral pharmaceutical composition comprising therapeutically effective amount of Bempedoic acid and pharmaceutically acceptable adjuvants, and wherein the composition is tablet.