Pharmaceutical Composition Dissolution via Acidifying Agents
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Solution Overview
Problem
The existing pharmaceutical compositions containing compound I exhibit poor dissolution properties in neutral aqueous solutions, which hinders their effectiveness as a therapeutic agent for thrombotic diseases.
Innovation Solution
Adjusting the proportion of compound I in the pharmaceutical composition to 0.5% to 10% by weight and incorporating sugar alcohols and water-swelling additives, along with coating agents like cellulose derivatives and polyvinyl compounds, enhances the dissolution rate in neutral pH conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compound I is used as an active ingredient in a pharmaceutical composition, then it exhibits potent inhibitory effect on activated factor X, but it shows reduced solubility and poor dissolution properties in neutral aqueous solution
Solution Approach 1:
The patent applies parameter changes by adjusting the pH of the dissolution medium to create an acidic environment (pH 5.0 or lower) that enhances the solubility and dissolution rate of compound I. This is achieved by incorporating acidifying agents into the pharmaceutical composition, which locally acidify the microenvironment around the drug substance, thereby resolving the contradiction between maintaining therapeutic effectiveness and improving dissolution properties in the physiological pH range.
2Quantity of substance
If compound I is used at higher concentrations to improve therapeutic effect, then potency increases, but dissolution properties in neutral region deteriorate further
Solution Approach 1:
The patent introduces acidifying agents as intermediary substances that mediate between the drug substance and the dissolution medium. These agents create a localized acidic microenvironment that facilitates dissolution without requiring changes to the bulk pH of the dissolution medium, thereby enabling higher concentrations of compound I to be incorporated while maintaining or improving dissolution properties.
3Productivity
If conventional coating methods are used to improve dissolution, then dissolution properties are enhanced, but the composition becomes more complex and manufacturing becomes more difficult
Solution Approach 1:
The patent merges the functions of dissolution enhancement and stabilization into a single approach by incorporating acidifying agents directly into the pharmaceutical composition matrix. This eliminates the need for separate coating layers or complex multi-component systems, thereby improving dissolution properties while maintaining composition simplicity and ease of manufacturing.
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 modified composition demonstrates improved dissolution properties in neutral pH, ensuring better bioavailability and therapeutic efficacy as an anticoagulant for treating thrombotic diseases.
Implementation Method 1
incorporating sugar alcohols and water-swelling additives
Implementation Method 2
water-swelling additives
Implementation Method 3
coating agents like cellulose derivatives and polyvinyl compounds
Data Source
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AI summary
It is desired to provide a pharmaceutical composition containing a compound represented by formula (I) or a pharmacologically acceptable salt thereof, or a solvate thereof, which exhibits an inhibitory effect on activated blood coagulation factor X (FXa), and is useful as an agent for preventing and/or treating thrombosis, wherein the pharmaceutical composition exhibits favorable dissolution properties. The present invention relates to a solid pharmaceutical composition containing a compound represented by formula (I) or a pharmacologically acceptable salt thereof, or a solvate thereof, wherein the content of the compound represented by formula (I) is 0.5% by weight or more and less than 15% by weight with respect to the total weight of the pharmaceutical composition.