Linagliptin-SGLT2 Tablet Composition for Excipient Stability
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Solution Overview
Problem
Pharmaceutical compositions of DPP-IV inhibitors like linagliptin face degradation issues with common excipients due to their reactive functional groups, leading to stability problems, especially in low dosage forms, necessitating improved formulations to ensure shelf life, content uniformity, and effective production.
Innovation Solution
A combination of linagliptin with a glucopyranosyl-substituted benzene derivative as an SGLT2 inhibitor, formulated with specific excipients, maintains stability and enables high content uniformity, effective production, and enhances bioavailability, resulting in solid pharmaceutical dosage forms like tablets and capsules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If linagliptin is formulated with common excipients in solid dosage forms, then the pharmaceutical composition can be produced and administered, but degradation and stability problems occur due to reactions between the amino group of linagliptin and excipients such as reducing sugars, carboxylic acid functional groups, and reactive carbonyl groups
Solution Approach 1:
The patent removes problematic excipients (reducing sugars, carboxylic acid-containing materials, reactive carbonyl groups) from the formulation entirely, replacing them with compatible alternatives that do not react with the amino group of linagliptin, thereby preventing degradation while maintaining manufacturability
Solution Approach 2:
The patent introduces compatible excipients as intermediaries that do not react with linagliptin's amino group, serving as safe mediators between the active ingredient and the formulation matrix, thus preventing direct harmful interactions
2Quantity of substance
If the dosage of linagliptin is reduced to achieve low dosage forms, then the therapeutic potency is optimized, but compatibility issues with excipients become more prominent and degradation problems increase
Solution Approach 1:
The patent changes the chemical composition parameters of the excipients selected for formulation, specifically choosing materials that lack reactive functional groups (reducing sugars, carboxylic acids, reactive carbonyl groups), thereby enabling stable low-dosage formulations where the drug-excipient ratio is high and interactions are magnified
3Productivity
If linagliptin reacts with excipients containing reducing sugars, carboxylic acid functional groups, or reactive carbonyl groups, then the pharmaceutical composition can be manufactured, but unexpected degradation and extraction problems occur
Solution Approach 1:
The patent takes preliminary action by systematically excluding excipients with known reactive functional groups (reducing sugars, carboxylic acids, reactive carbonyl groups) from the formulation palette before manufacturing begins, preventing degradation problems from occurring in the first place rather than addressing them after they manifest
Data Source
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AI summary
The present invention relates to pharmaceutical compositions of linagliptin, pharmaceutical dosage forms, their preparation, their use and methods for treating metabolic disorders.