Pharmaceutical Composition with Hydroxypropyl-Beta-Cyclodextrin
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Solution Overview
Problem
There is a lack of a pharmaceutical composition that effectively combines 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or its pharmaceutically acceptable salt with hydroxypropyl-β-cyclodextrin, which provides stability, disintegratability, and absorbability, while being easily prepared for oral administration.
Innovation Solution
A pharmaceutical composition containing 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or its pharmaceutically acceptable salt combined with hydroxypropyl-β-cyclodextrin, which is physically mixed to create a stable, easily prepared, and highly absorbable formulation, characterized by specific diffraction angles, chemical shifts, and absorption bands, suitable for oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a hydrophobic compound is formulated using conventional cyclodextrin liquid formulations, then solubility is improved, but formulation complexity and manufacturing difficulty increase
Solution Approach 1:
The patent changes the physical state parameter of the cyclodextrin formulation from liquid to solid by using hydroxypropyl-β-cyclodextrin solid particles. This parameter change maintains the solubility enhancement capability while eliminating the complexity associated with liquid formulation handling, stabilization, and administration. The solid form allows for simpler manufacturing processes and better storage stability.
2Ease of manufacture
If solid formulations with physically added cyclodextrin are used, then manufacturing is simplified, but solubility improvement is insufficient
Solution Approach 1:
The patent applies the nesting principle by incorporating the hydrophobic compound (guest molecule) inside the cyclodextrin cavity (host molecule) to form an inclusion complex. This nested structure allows the hydrophobic compound to be embedded within the hydrophilic cyclodextrin cavity, enabling solid formulation while maintaining enhanced solubility. The physical mixing of hydroxypropyl-β-cyclodextrin solid particles with the compound creates this nested arrangement that simplifies manufacturing compared to liquid formulations.
3Quantity of substance
If liquid cyclodextrin formulations are used for oral administration, then solubility is enhanced, but stability and disintegratability are compromised
Solution Approach 1:
The patent utilizes phase transition by converting the cyclodextrin formulation from liquid phase to solid phase through the use of hydroxypropyl-β-cyclodextrin solid particles. This phase transition maintains the solubility enhancement benefits of cyclodextrin inclusion complexes while providing the stability and disintegratability characteristics of solid formulations. The solid particles can be easily administered orally and maintain compositional stability during storage and handling.
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 excellent stability, disintegratability, and absorbability, with improved solubility and bioavailability, making it suitable for treating tumors and inhibiting c-Met and VEGFR2.
Implementation Method 1
Cyclodextrins and derivatives thereof are widely generally known as an excipient for improving the solubility of a hydrophobic compound in water
Data Source
AI summary
An object of the present invention is to provide a pharmaceutical composition which has excellent stability, disintegratability, and absorbability, is easily prepared, and contains 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and a cyclodextrin derivative. The present invention relates to a pharmaceutical composition containing 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide or a pharmaceutically acceptable salt thereof and hydroxypropyl-β-cyclodextrin.