High-Dose Basic Drug Tablets With Surfactant-Aided Dissolution
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Solution Overview
Problem
Poorly soluble basic agents, such as the compound represented by formula (I), face challenges in achieving high-dose formulations with good disintegration and dissolution, leading to low oral absorbability due to the formation of impermeable films during tablet disintegration.
Innovation Solution
A pharmaceutical composition comprising a compound represented by formula (I) or its salt, an anionic surfactant like sodium lauryl sulfate, and a basic substance such as magnesium aluminometasilicate, with specific weight ratios and amounts, to prevent film formation and enhance dissolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a high-dose formulation is used to increase absorption of a poorly soluble basic agent, then the dosage strength is improved, but the dissolution and oral absorbability worsen due to stronger poor solubility at high doses
Solution Approach 1:
A water-soluble basic substance (mediator) is introduced into the formulation to interact with the poorly soluble basic agent. This intermediary substance forms a soluble complex or salt with the drug compound, enabling high-dose formulations to dissolve properly in gastrointestinal fluids. The mediator bridges the gap between the insoluble drug and the aqueous environment needed for absorption.
Solution Approach 2:
The formulation changes the chemical parameters of the poorly soluble basic agent by converting it into a soluble form through interaction with the water-soluble basic substance. This parameter change (from insoluble to soluble state) enables high-dose formulations to maintain good dissolution properties despite the increased drug load.
2Ease of manufacture
If a poorly soluble basic agent is compressed into tablets, then the formulation is improved for oral administration, but an impermeable film forms during disintegration that prevents further dissolution
Solution Approach 1:
The water-soluble basic substance acts as an intermediary that prevents film formation during tablet disintegration. It interacts with the poorly soluble basic agent to maintain solubility throughout the disintegration process, ensuring that no impermeable film forms to block further dissolution. This mediator ensures continuous solubility from tablet disintegration through to complete dissolution.
3Reliability
If dissolution aids are used to improve dissolution of poorly soluble basic agents, then the dissolution rate is improved, but the formulation complexity increases
Solution Approach 1:
The water-soluble basic substance serves multiple functions simultaneously: it acts as a dissolution aid to improve dissolution rate, as a formulation enabler to allow high-dose formulations, and as a solubility enhancer to prevent film formation. This multi-functionality reduces the need for multiple separate additives, thereby simplifying the overall formulation despite achieving multiple goals.
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 composition achieves high-dose tablets with good dissolution and disintegration, reducing dosing frequency and improving drug compliance by preventing impermeable film formation and enhancing oral absorbability.
Implementation Method 1
A pharmaceutical formulation which comprises, as an active ingredient, a poorly soluble basic agent such as compound (I) or a salt thereof typically has low absorption when orally administered
Data Source
AI summary
The present invention aims to provide a high-dose formulation with improved properties of a pharmaceutical composition comprising a poorly soluble basic agent, particularly a compound represented by formula (I) or a salt thereof. The problem described above can be solved by providing a pharmaceutical composition comprising the compound represented by formula (I) or a salt thereof, a surfactant, and a basic substance.