Hydroxypropyl-beta-cyclodextrin Inclusion Complex for KX2-361 Oral Preparation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
KX2-361, a poorly soluble compound used to treat cell proliferative diseases, faces challenges in water solubility, leading to low bioavailability and absorption issues when administered orally, and existing solubilization methods are not effective for its development as a cost-effective drug preparation.
Innovation Solution
An oral preparation method using hydroxypropyl-β-cyclodextrin to form an inclusion complex with KX2-361 or its medicinal salts, optimizing the molar ratio and concentration to enhance solubility, stability, and bioavailability, and incorporating excipients like microcrystalline cellulose, lactose, and magnesium stearate for tablet formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If KX2-361 is administered orally in its free base or medicinal salt form, then the drug can be delivered to patients, but the poor water solubility causes low bioavailability and poor absorbability
Solution Approach 1:
The patent uses cyclodextrins as intermediary substances to form inclusion complexes with KX2-361. The cyclodextrin molecules create a host-guest complex where the hydrophobic drug molecule is encapsulated within the cyclodextrin cavity, enabling the poorly soluble drug to be transported in aqueous environments with improved bioavailability
Solution Approach 2:
The patent changes the physical and chemical parameters of the drug delivery system by forming inclusion complexes. This transforms the drug from a poorly soluble free base or salt form into a soluble complex form, fundamentally altering the solubility parameter while maintaining the drug's pharmacological activity
2Quantity of substance
If various solubilization methods are used for KX2-361, then water solubility may be improved, but the complexity of preparation and production costs increase
Solution Approach 1:
The patent employs cyclodextrins as simple, cost-effective solubilizing agents that can be easily incorporated into the drug formulation. The inclusion complex preparation process is straightforward, avoiding complex equipment and multi-step procedures, thereby reducing both preparation complexity and production costs
Solution Approach 2:
The patent creates a composite material system consisting of cyclodextrin and KX2-361 in a specific molar ratio (1:1 to 1:10). This composite inclusion complex combines the solubilizing properties of cyclodextrin with the therapeutic activity of KX2-361, achieving effective solubility enhancement through a simple composite formulation
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 method significantly improves the solubility and bioavailability of KX2-361, allowing for stable and effective oral and intravenous drug preparations with high safety and bioavailability, and reduces production costs.
Implementation Method 1
hydroxypropyl-β-cyclodextrin and an active ingredient that is KX2-361 or a medicinal salt thereof, wherein at least part of the active ingredient is encapsulated by at least a part of the hydroxypropyl-β-cyclodextrin to form a drug inclusion complex
Data Source
AI summary
An oral preparation for treating cell proliferation diseases. The oral preparation comprises hydroxylpropoxyl-β-cyclodextrin and an active component. The active component is KX2-361 or a medicinal salt thereof, and KX2-361 is represented by formula 1. By mixing hydroxylpropoxyl-ydcyclodextrin with KX2-361 or the medicinal salt thereof, an inclusion complex is formed, the solubility of the poorly-soluble drug KX2-361 is greatly improved, and accordingly the drug is prepared into an oral preparation. The oral preparation has good stability, high safety, good absorbability, high bioavailability and economical cost.