Dispersible Alpelisib Tablets With High Drug Loading and Fast Dispersion
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Solution Overview
Problem
Existing oral formulations of (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) are impractical for patients with swallowing difficulties, such as children and elderly individuals, necessitating alternative dosage forms for convenient and effective administration.
Innovation Solution
Development of a dispersible tablet formulation containing (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) with high drug loading, dispersing in aqueous media within minutes, using sodium starch glycolate, low-substituted hydroxypropyl cellulose, and sodium stearyl fumarate, suitable for administration via liquid dispersion or feeding tubes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Compound I is administered as a solid tablet, then it provides stable and convenient administration, but it cannot be conveniently administered to patients with swallowing difficulties
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using amorphous Compound I instead of crystalline form, and by formulating it in a dispersible tablet format with specific excipients. This transforms the dosage form from a swallowable solid tablet to a dispersible formulation that can be administered to patients with swallowing difficulties while maintaining stability and convenience.
2Quantity of substance
If Compound I is formulated with high drug loading, then the tablet size is reduced, but the disintegration time increases
Solution Approach 1:
The patent achieves high drug loading (30-50% w/w) while maintaining rapid disintegration (≤5 minutes) by changing the physical state of Compound I to amorphous form and using a specific combination of excipients including disintegrants and hydrophilic polymers. This parameter change in the formulation allows both high drug concentration and rapid disintegration to coexist.
Solution Approach 2:
The patent uses a composite formulation containing amorphous Compound I combined with specific excipients (disintegrants like croscarmellose sodium, hydrophilic polymers like HPMC) that work synergistically. This composite material structure enables high drug loading while maintaining rapid disintegration properties through the combined effects of the amorphous drug form and the excipient system.
3Adaptability or versatility
If Compound I is administered in liquid form, then it can be given to patients with swallowing difficulties, but the stability and convenience of solid dosage forms are lost
Solution Approach 1:
The patent changes the physical state of Compound I to amorphous form and formulates it in a dispersible tablet that disperses in liquid to form a suspension. This maintains the stability advantages of solid dosage forms during storage while providing liquid-like administerability to patients with swallowing difficulties, thus resolving the contradiction between stability and adaptability.
Data Source
AI summary
The present invention relates to dispersible tablets comprising the compound (S)-Pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or a pharmaceutically acceptable salt thereof.