Amorphous Dapagliflozin Solid Dispersion Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current pharmaceutical compositions of dapagliflozin face challenges in achieving optimal bioavailability, inter-patient variability, safety, stability, and processability due to polymorphic forms, with amorphous forms being hygroscopic and having a low glass transition temperature, affecting dissolution profiles and storage stability.
Innovation Solution
Development of amorphous solid dispersions and adsorbates of dapagliflozin with suitable polymers like PVP, PVA, and HPMC, which are stable and do not form inclusion complexes, ensuring improved chemical stability and dissolution profiles, and can be prepared using fluid bed granulation and adsorption processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If amorphous forms of dapagliflozin are used, then dissolution rate is improved, but storage stability deteriorates due to hygroscopicity and low glass transition temperature
Solution Approach 1:
The patent combines amorphous dapagliflozin with specific polymers (PVP, PVA, HPMC) to create composite solid dispersions. The polymer matrix provides structural stability and reduces hygroscopicity while maintaining the amorphous state of dapagliflozin, thus improving both dissolution rate and storage stability simultaneously.
Solution Approach 2:
The polymer acts as an intermediary between amorphous dapagliflozin and the external environment. It prevents direct interaction with moisture and reduces the impact of low glass transition temperature, thereby stabilizing the amorphous form during storage while allowing rapid dissolution when administered.
2Stability of the object's composition
If crystalline forms of dapagliflozin are used, then storage stability is improved, but bioavailability deteriorates
Solution Approach 1:
The patent changes the physical state parameter of dapagliflozin from crystalline to amorphous, and further optimizes it by incorporating into polymer matrices. This parameter change transforms the material properties to achieve both high bioavailability through improved dissolution and adequate storage stability through polymer protection.
3Productivity
If amorphous solid dispersions are prepared, then dissolution profile is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies local quality by selecting specific polymers with particular properties (PVP, PVA, HPMC) that are compatible with standard manufacturing processes. The polymer choice is optimized locally to enable amorphous solid dispersion formation through conventional techniques like fluid bed granulation, rather than requiring entirely new manufacturing approaches.
Solution Approach 2:
The patent extracts the complexity of amorphous form stabilization by isolating it into a separate polymer matrix component. This allows the dapagliflozin to be processed in its amorphous state within the polymer framework using standard pharmaceutical manufacturing techniques, reducing overall manufacturing complexity.
4Stability of the object's composition
If polymers like PVP, PVA, and HPMC are used to stabilize amorphous dapagliflozin, then chemical stability is improved, but formulation complexity increases
Solution Approach 1:
The selected polymers (PVP, PVA, HPMC) serve multiple functions simultaneously: they stabilize the amorphous form, control dissolution rate, provide structural integrity to the formulation, and are compatible with standard manufacturing processes. This multi-functionality reduces the need for additional excipients and simplifies the overall formulation despite the complexity of stabilizing amorphous dapagliflozin.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The amorphous solid dispersions and adsorbates exhibit enhanced stability, content uniformity, and improved dissolution rates, overcoming the limitations of crystalline forms and hygroscopicity, making them suitable for tropical climates and improved storage conditions.
Implementation Method 1
amorphous solid dispersions and adsorbates of dapagliflozin with suitable polymers like PVP, PVA, and HPMC, which are stable and do not form inclusion complexes
Implementation Method 2
adsorbates of dapagliflozin with suitable polymers... prepared using fluid bed granulation and adsorption processes
Implementation Method 3
prepared using fluid bed granulation and adsorption processes
Data Source
Figure 1~2
Figure 3~4
Figure 5~6
AI summary
The present invention belongs to the field of pharmaceutical industry and relates to an amorphous solid dispersion comprising at least one polymer and dapagliflozin, to a pharmaceutical composition comprising said solid dispersion, to a process for the preparation thereof, and to the solid dispersion and pharmaceutical composition respectively obtainable by said process. Further, the present invention refers to an adsorbate comprising dapagliflozin and to a pharmaceutical composition comprising said adsorbate, as well as to a process for the preparation thereof. Finally, the present invention relates to the solid dispersion, the adsorbate or the pharmaceutical composition for use in the treatment of diseases related to hypoglycemia.