High-Load AG10 Tablet Formulation for Stable Dissolution
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Solution Overview
Problem
Current pharmaceutical formulations of AG10, a potential treatment for TTR amyloid-related diseases, lack stability and consistency in pharmacokinetic data, and existing tablets with high AG10 loads suffer from erosion and reduced dissolution rates during storage.
Innovation Solution
Development of high-load tablet formulations of AG10 using high-grade microcrystalline cellulose and specific excipients, including fillers, binders, and lubricants, with optional coating, to enhance stability and dissolution properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high-load tablet formulations of AG10 are developed, then the dosage strength is improved, but the tablet stability and dissolution rate deteriorate during storage
Solution Approach 1:
The patent applies parameter changes by systematically varying formulation parameters including excipient types (microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate), coating materials (hypromellose, titanium dioxide, triacetin), and processing conditions to achieve optimal stability and dissolution properties for high-load AG10 tablets
Solution Approach 2:
The patent employs composite materials by combining multiple excipients and coating agents with AG10 to create a stable tablet formulation. The composite structure includes core excipients for tablet matrix, disintegrants for breakdown, and coating layers for protection, all working together to maintain tablet integrity while enabling high drug load
2Quantity of substance
If high-load tablet formulations of AG10 are developed, then the dosage strength is improved, but the dissolution rate decreases during storage
Solution Approach 1:
The patent optimizes dissolution rate by adjusting formulation parameters including the type and amount of disintegrant (croscarmellose sodium), binder (hydroxypropyl cellulose), and coating composition (hypromellose, titanium dioxide, triacetin) to maintain rapid drug release even in high-load formulations
Solution Approach 2:
The patent applies local quality by creating a specialized coating layer with specific properties (hypromellose, titanium dioxide, triacetin) that protects the tablet core while maintaining dissolution rate, and by using different excipients in different regions of the tablet formulation to optimize both stability and release characteristics
3Ease of manufacture
If existing tablet formulations are used, then manufacturing simplicity is maintained, but pharmacokinetic consistency deteriorates
Solution Approach 1:
The patent achieves pharmacokinetic consistency by optimizing critical formulation parameters including the ratio of microcrystalline cellulose to hydroxypropyl cellulose, the amount of croscarmellose sodium disintegrant, and the coating composition (hypromellose, titanium dioxide, triacetin), while maintaining a manufacturable tablet pressing process
Solution Approach 2:
The patent applies preliminary action by pre-coating tablets with a specific composition (hypromellose, titanium dioxide, triacetin) before final pressing, and by pre-mixing excipients in specific ratios to ensure consistent pharmacokinetic profiles while maintaining ease of manufacture
Data Source
AI summary
The present disclosure provides high-load tablet formulations of AG10 or a pharmaceutically acceptable salt thereof. In some aspects, provided herein are table formulations of AG10 or a pharmaceutically acceptable salt thereof that include at least 40% or more AG10 by weight and at least one pharmaceutical excipient selected from one or more fillers, one or more binders, one or more disintegrants, and one or more lubricants.