Metformin Sitagliptin Compartmentalized Dosage Form
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Solution Overview
Problem
Current pharmaceutical compositions of metformin and sitagliptin for type II diabetes treatment often cause gastrointestinal adverse effects due to high drug concentrations, and existing formulations fail to provide an optimal release profile that minimizes these side effects while maintaining effective glucose control.
Innovation Solution
A pharmaceutical composition with separate compartments containing metformin and sitagliptin, where at least one compartment represents an extended release composition, avoiding core coatings and allowing independent dissolution profiles for each API, thereby reducing peak concentrations and improving patient adherence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If immediate-release metformin formulations are used, then the drug releases quickly within 1-2 hours after dosing, but this results in high drug concentrations in the GI tract causing gastrointestinal adverse effects
Solution Approach 1:
The tablet is divided into two separate compartments: an inner core compartment containing metformin and an outer coating compartment containing sitagliptin. This segmentation allows the metformin to be released in a controlled manner while the sitagliptin provides immediate release, thereby reducing gastrointestinal adverse effects while maintaining effective glucose control.
Solution Approach 2:
The patent changes the release parameters of metformin from immediate-release to extended-release by using a sustained-release polymer coating. This parameter change reduces the peak concentration of metformin in the GI tract, thereby reducing gastrointestinal adverse effects while maintaining effective glucose control over a longer period.
2Reliability
If high doses of metformin are used to achieve effective glucose control, then glucose control is improved, but gastrointestinal adverse effects increase and may cause patients to discontinue therapy
Solution Approach 1:
The patent changes the release profile of metformin from immediate-release to extended-release, which maintains effective glucose control over a longer period while reducing peak concentrations in the GI tract. This allows for effective glucose control with reduced gastrointestinal adverse effects.
Solution Approach 2:
The patent uses a composite structure combining metformin with a sustained-release polymer and sitagliptin. This composite formulation allows for controlled release of metformin and immediate release of sitagliptin, providing effective glucose control while reducing gastrointestinal adverse effects.
3Duration of action of moving object
If sustained-release polymer coating is applied to metformin core, then extended release of metformin is achieved, but the manufacturing process becomes more complex
Solution Approach 1:
The tablet is segmented into an inner core compartment and an outer coating compartment, each with distinct functions. The inner core contains metformin for extended release, while the outer coating contains sitagliptin for immediate release. This segmentation simplifies the manufacturing process by allowing independent formulation and coating steps.
Solution Approach 2:
The sitagliptin-containing coating is applied as a layer around the metformin-containing core, creating a nested structure. This nested design allows for extended release of metformin from the core while providing immediate release of sitagliptin from the outer coating, achieving dual release profiles in a single tablet.
4Reliability
If sitagliptin is included in the formulation, then DPP-IV inhibition and glucose control are improved, but the risk of adverse effects from DPP-IV inhibition increases
Solution Approach 1:
The patent uses immediate-release sitagliptin to achieve rapid DPP-IV inhibition and glucose control. By combining immediate-release sitagliptin with extended-release metformin, the formulation provides effective glucose control while the metformin component helps mitigate gastrointestinal adverse effects.
Solution Approach 2:
The patent creates a composite formulation combining metformin and sitagliptin in a specific ratio and release profile. The sitagliptin provides immediate DPP-IV inhibition for effective glucose control, while the metformin provides extended glucose control with reduced gastrointestinal adverse effects, creating a synergistic effect.
Data Source
AI summary
The present invention relates to a pharmaceutical composition, preferably a pharmaceutical dosage form, comprising at least two separate compartments, wherein one compartment contains a composition comprising metformin or a pharmaceutically acceptable salt thereof and wherein another compartment contains a composition comprising sitagliptin.The present invention also relates to a process for preparing dosage forms comprising metformin or a pharmaceutically acceptable salt thereof and sitagliptin or a pharmaceutically acceptable salt thereof, the process comprising the steps of:a) providing one composition containing metformin or a pharmaceutically acceptable salt thereof and optionally also sitagliptin,b) providing a further composition containing sitagliptin or a pharmaceutically acceptable salt thereof and optionally also metformin, andc) combining the compositions to form compartments.The present invention also refers to a process for preparing dosage forms comprising at least one compartment comprising metformin or a pharmaceutically acceptable salt thereof and sitagliptin or a pharmaceutically acceptable salt thereof, the process comprises providing a composition containing metformin or a pharmaceutically acceptable salt thereof, and sitagliptin or a pharmaceutically acceptable salt thereof, and a matrix agent.Moreover, the present invention related to a dosage form obtained by said process, and to the use of said dosage form for the treatment of diabetes.