Amorphous Dapagliflozin Formulation for Stability and Dissolution
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Solution Overview
Problem
Existing solid forms of dapagliflozin face challenges in bioavailability, stability, and uniformity, particularly due to polymorphic forms affecting dissolution rate and flow properties, which are not adequately addressed in prior pharmaceutical formulations.
Innovation Solution
A solid pharmaceutical formulation comprising amorphous dapagliflozin with specific particle size ranges and combined with pharmaceutically acceptable excipients such as microcrystalline cellulose, lactose, and magnesium stearate, which enhances stability, bioavailability, and content uniformity, thereby improving the dissolution profile and compressibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If crystalline forms of dapagliflozin are used, then stability is improved, but dissolution rate and bioavailability worsen
Solution Approach 1:
The patent changes the physical state parameter of dapagliflozin from crystalline to amorphous form. This parameter change resolves the contradiction by achieving both improved dissolution rate and bioavailability while maintaining acceptable stability through specific formulation conditions including controlled water activity and use of particular excipients.
2Productivity
If amorphous forms of dapagliflozin are used, then dissolution rate is improved, but stability and water activity control worsen
Solution Approach 1:
The patent introduces excipients as intermediary substances that stabilize the amorphous form of dapagliflozin. These excipients control water activity and prevent crystallization, thereby maintaining the high dissolution rate of the amorphous form while improving stability. The excipients act as mediators between the amorphous drug form and the environmental conditions.
Solution Approach 2:
The patent creates a composite pharmaceutical formulation combining amorphous dapagliflozin with specific excipients. This composite material approach allows the formulation to exhibit both the high dissolution rate of amorphous drug and the stability provided by the excipient matrix, resolving the contradiction between dissolution performance and stability.
3Adaptability or versatility
If polymorphic forms of dapagliflozin are used, then manufacturing flexibility is improved, but content uniformity and flow properties worsen
Solution Approach 1:
The patent extracts the polymorphic variability issue by selecting and fixing on a single amorphous form of dapagliflozin. This extraction of the problematic degree of freedom (polymorphism) simplifies the manufacturing process and improves content uniformity, while the amorphous nature maintains manufacturing flexibility through ease of processing.
Data Source
AI summary
The present invention relates to a solid pharmaceutical formulation comprising amorphous dapagliflozin and at least one pharmaceutically acceptable excipient. Further, the formulations comprising amorphous dapagliflozin are prepared a method which is simple, rapid, cost effective, time-saving and industrially convenient process.