Bilayer Sacubitril-Valsartan Tablet for Stable SGLT-2 Coformulation
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Solution Overview
Problem
Existing formulations of sacubitril-valsartan and SGLT-2 inhibitors have poor stability and solubility, limiting their effectiveness in treating heart failure, and there is a need for a combination formulation that maintains synergistic effects while ensuring stability and equivalent dissolution profiles.
Innovation Solution
A pharmaceutical combination formulation comprising a first release portion with sacubitril-valsartan and a second release portion with an SGLT-2 inhibitor, physically separated and potentially in a bilayer or drug-coated tablet form, using specific excipients, disintegrants, and lubricants to enhance stability and dissolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If sacubitril-valsartan and SGLT-2 inhibitor are combined in a single formulation, then synergistic treatment effect for heart failure is achieved, but stability and dissolution rate deteriorate
Solution Approach 1:
The tablet is divided into two distinct layers: a first layer containing sacubitril-valsartan and a second layer containing SGLT-2 inhibitor. This segmentation prevents direct interaction between the two drugs, maintaining stability while enabling synergistic treatment when both layers are ingested together.
Solution Approach 2:
Each layer is formulated with specific excipients and disintegrants optimized for its particular drug's dissolution characteristics. The first layer uses excipients suited for sacubitril-valsartan release while the second layer uses excipients optimized for SGLT-2 inhibitor release, allowing each drug to maintain its optimal dissolution profile.
2Reliability
If sacubitril-valsartan and SGLT-2 inhibitor are combined in a single formulation, then synergistic treatment effect for heart failure is achieved, but dissolution rate deteriorates
Solution Approach 1:
The tablet is divided into two distinct layers: a first layer containing sacubitril-valsartan and a second layer containing SGLT-2 inhibitor. This segmentation prevents direct interaction between the two drugs, maintaining stability while enabling synergistic treatment when both layers are ingested together.
Solution Approach 2:
Each layer is formulated with specific excipients and disintegrants optimized for its particular drug's dissolution characteristics. The first layer uses excipients suited for sacubitril-valsartan release while the second layer uses excipients optimized for SGLT-2 inhibitor release, allowing each drug to maintain its optimal dissolution profile.
3Stability of the object's composition
If physical separation of drug layers is implemented, then stability is improved, but device complexity increases
Solution Approach 1:
Two separately formulated layers, each optimized for a specific drug's stability and dissolution, are compressed together to form a single integrated tablet. This merging maintains the stability benefits of physical separation while presenting a simple unit-dose formulation to the patient.
Solution Approach 2:
The tablet is divided into two distinct layers: a first layer containing sacubitril-valsartan and a second layer containing SGLT-2 inhibitor. This segmentation prevents direct interaction between the two drugs, maintaining stability while enabling synergistic treatment when both layers are ingested together.
Data Source
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AI summary
The present invention relates to a pharmaceutical combination formulation which has a synergistic effect in the treatment of heart failure by containing both sacubitril-valsartan and an SGLT-2 inhibitor as active ingredients, and at the same time, ensures bioequivalence between the drugs because the effect of one drug on the dissolution of the other drug is minimized. In addition, the generation of impurities in the pharmaceutical combination formulation is inhibited, and thus the stability of the active ingredients is also excellent.