Oral Solution pH Adjustment for Poorly Soluble Drug
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Solution Overview
Problem
The challenge is to create a pharmaceutical solution for oral administration of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or its salt, which is poorly soluble in water and has a bitter taste, suitable for patients with central neurological diseases like schizophrenia, who have difficulty swallowing solid agents and require a formulation that facilitates dose determination and taste masking.
Innovation Solution
The solution involves adding lactic acid, phosphoric acid, or other acids to adjust the pH to 2.5-4.5, incorporating glycine for buffering, and including flavor-enhancing agents to improve solubility and taste, resulting in an aqueous solution that maintains stability and flavor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If compound (I) or its salt is formulated as a solid agent for oral administration, then the drug can be administered effectively, but patients with central neurological diseases have difficulty swallowing it
Solution Approach 1:
The invention transitions the drug formulation from solid phase (tablets, capsules) to liquid phase (oral solution). This phase transition eliminates the swallowing difficulty associated with solid agents while maintaining effective drug delivery for central neurological diseases.
2Ease of operation
If compound (I) or its salt is dissolved in water to create an oral solution, then ease of administration is improved, but the drug's poor water solubility prevents effective solubilization
Solution Approach 1:
The invention changes the pH parameter of the aqueous solution to within the range of 2.5-4.5, which significantly enhances the solubility of compound (I) or its salt. This parameter change enables effective solubilization while maintaining the liquid formulation form for easy administration.
Solution Approach 2:
The invention introduces buffering agents (such as citric acid, phosphoric acid, or their salts) as intermediaries to maintain the pH within the optimal range of 2.5-4.5. These buffering agents mediate between the drug's solubility requirements and the stability of the oral solution.
3Ease of operation
If compound (I) or its salt is formulated as an oral solution, then handling and dose determination are facilitated, but the drug has a bitter taste that makes it difficult to take
Solution Approach 1:
The invention introduces flavor-enhancing and/or masking agents as intermediaries to counteract the bitter taste of compound (I) or its salt. These agents mediate between the drug's inherent bitterness and the patient's taste perception, making the oral solution palatable and easy to take.
4Quantity of substance
If the pH of the oral solution is adjusted to enhance solubility, then solubility is improved, but pH variation upon dilution can cause precipitation of the compound
Solution Approach 1:
The invention introduces buffering agents (citric acid, phosphoric acid, or their salts) as intermediaries to maintain pH stability within the range of 2.5-4.5. These buffers act as mediators that resist pH changes upon dilution, preventing precipitation while maintaining enhanced solubility.
Solution Approach 2:
The invention incorporates buffering capacity in advance to cushion against pH variations that would occur upon dilution. This prior cushioning prevents the pH from shifting outside the optimal range, thereby preventing precipitation before it can occur.
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 solution enhances the solubility and stability of the compound, maintains pH stability upon dilution, and masks the bitter taste, making it easier for patients to administer and tolerate.
Implementation Method 1
adding thereto at least one compound selected from the group consisting of lactic acid, phosphoric acid, glycolic acid, malic acid, tartaric acid, citric acid, succinic acid and acetic acid and adjusting the pH thereof to 2.5-4.5
Implementation Method 2
a superior buffering ability can be obtained by adding glycine to the solution. Furthermore, they have found that a solution having a less bitter taste, which is easy to take and affords the above-mentioned effect
Implementation Method 3
a solution having a less bitter taste, which is easy to take and affords the above-mentioned effect, can be obtained by adding at least one flavor enhancing and/or masking agent to the solution
Data Source
AI summary
Provided is a solution suitable for oral administration of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one(compound (I)) or a salt thereof. A solution for oral administration containing compound (I) or a salt thereof, and at least one compound selected from the group consisting of lactic acid, phosphoric acid, glycolic acid, malic acid, tartaric acid, citric acid, succinic acid and acetic acid and having pH 2.5-4.5.