Sitagliptin Maleate Tablet Composition With Low Moisture Retention
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Solution Overview
Problem
Existing solid oral pharmaceutical compositions of DPP-4 inhibitors, particularly sitagliptin, face challenges with stability due to moisture sensitivity and reduced bioavailability due to the use of hygroscopic excipients like polyvinylpyrrolidone and magnesium stearate, which also compromise tablet strength and solubility.
Innovation Solution
Formulations are developed using sitagliptin maleate in polymorph form, free of polyvinylpyrrolidone and magnesium stearate, combined with excipients like microcrystalline cellulose and dibasic calcium phosphate anhydrate, to enhance stability, solubility, and bioavailability, while maintaining low moisture retention and safe components for hypertensive and cardiac patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If hygroscopic excipients like polyvinylpyrrolidone and magnesium stearate are used, then tablet strength and flowability are improved, but moisture retention increases and stability decreases
Solution Approach 1:
The patent removes hygroscopic excipients (polyvinylpyrrolidone and magnesium stearate) from the formulation entirely, replacing them with non-hygroscopic alternatives like microcrystalline cellulose and dibasic calcium phosphate anhydrate, thereby eliminating the source of moisture retention while maintaining tablet integrity
Solution Approach 2:
The patent changes the physical and chemical parameters of the formulation by selecting excipients with different hygroscopic properties, specifically using materials with low moisture affinity to reduce overall moisture retention in the tablet composition
2Ease of manufacture
If hygroscopic excipients are used to improve manufacturing properties, then ease of manufacture is improved, but bioavailability decreases due to reduced solubility
Solution Approach 1:
The patent eliminates hygroscopic excipients that interfere with drug solubility and bioavailability, replacing them with excipients that do not compromise the drug's dissolution properties
Solution Approach 2:
The patent uses a composite formulation combining multiple non-hygroscopic excipients (microcrystalline cellulose, dibasic calcium phosphate anhydrate, colloidal silicon dioxide, sodium stearyl fumarate) that collectively provide manufacturing benefits without the negative effects of individual hygroscopic materials
3Manufacturing precision
If sitagliptin HCl salt is used to increase stability by lowering impurity ratio, then purity is improved, but moisture retention capacity increases 3-10 times compared to other salts
Solution Approach 1:
The patent changes the salt form parameter of sitagliptin from hydrochloride to maleate, which fundamentally alters the moisture retention characteristics while maintaining or improving stability and solubility properties
Solution Approach 2:
The patent selects a specific salt form (maleate) that provides localized improvement in moisture stability while maintaining the desired purity profile, addressing the specific problem of excessive moisture retention in the hydrochloride form
Data Source
AI summary
The present invention relates to solid oral pharmaceutical compositions comprising at least one DPP-4 inhibitor, particularly sitagliptin, or a pharmaceutically acceptable salt thereof, providing ease of manufacture and high stability.