Dry-Granulated Tablet Formulations for Higher Drug Loading
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pharmaceutical formulations of the compound of Formula I suffer from low drug loading, leading to larger tablet sizes and increased number of tablets required per dose, which affects patient compliance and manufacturability due to the dominance of excipient properties over the API's physical properties.
Innovation Solution
A pharmaceutical formulation comprising the compound of Formula I with a drug loading of 40-70 wt%, along with specific ratios of a filler, disintegrating agent, and lubricant, such as microcrystalline cellulose, crospovidone, and magnesium stearate, allowing for high drug loading tablets to be produced using a dry granulation process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If wet granulation process is used to formulate the compound of Formula I, then the formulation can be manufactured, but the drug loading is low (24.4%) and tablet size is large
Solution Approach 1:
The patent changes the drug loading parameter from 24.4% to 40-70%, and switches the manufacturing process from wet granulation to dry granulation. This parameter change enables high drug loading while maintaining manufacturability through the dry granulation process, resolving the contradiction between ease of manufacture and quantity of substance.
Solution Approach 2:
The patent replaces the wet granulation mechanical system with a dry granulation mechanical system. This substitution eliminates the need for binders and moisture control, enabling higher drug loading (40-70%) while maintaining ease of manufacture through a simplified process that doesn't require water or organic solvents.
2Volume of moving object
If drug loading is increased to reduce tablet size, then patient compliance improves, but the physical properties of the API become predominant and manufacturability becomes difficult
Solution Approach 1:
The patent replaces wet granulation with dry granulation, which substitutes the mechanical system that relies on binder adhesion and moisture control with a system based on mechanical compaction and binding during tablet compression. This enables high drug loading (40-70%) and small tablet size while maintaining ease of manufacture, as the dry granulation process inherently handles the physical properties of the API without requiring additional binders.
Solution Approach 2:
The patent extracts and eliminates the binder component from the formulation by using dry granulation instead of wet granulation. This removal of the binder requirement allows the API's own physical properties to be充分利用ed, enabling high drug loading while maintaining manufacturability through direct compression or dry granulation followed by compression.
3Ease of manufacture
If more excipients are added to improve manufacturability, then the formulation is easier to manufacture, but the drug loading decreases and tablet size increases
Solution Approach 1:
The patent extracts and removes the binder excipient from the formulation by implementing dry granulation. This eliminates the need for additional excipients that would otherwise be required to achieve manufacturability, thereby maintaining ease of manufacture while maximizing drug loading to 40-70% and reducing tablet size.
Data Source
AI summary
Pharmaceutical formulations, particularly solid oral dosage forms (e.g., tablets) comprising (i) the compound of Formula I in an amount of about 40 wt % to about 70 wt %, (ii) a filler, (iii) a disintegrating agent, (iv) and a lubricant are disclosed, as are uses thereof.