Paclitaxel Cyclodextrin Inclusion Complex Solubility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current paclitaxel/cyclodextrin inclusion complexes face challenges such as low solubility, poor pharmaceutical stability, high cyclodextrin proportions, and residual organic solvents, limiting their clinical application.
Innovation Solution
A pharmaceutical composition comprising paclitaxel and hydroxypropyl-sulfobutyl-β-cyclodextrin or sulfobutyl-β-cyclodextrin with a mass ratio of 1:10 to 150, where the inclusion complex is prepared by dissolving paclitaxel in an aqueous solution of the cyclodextrin and removing ethanol under reduced pressure to achieve a stable and highly soluble paclitaxel/cyclodextrin inclusion with low residual organic solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If paclitaxel is formulated using polyoxyethylene castor oil and anhydrous alcohol as solvents, then the drug can be administered through injection, but it causes high incidence of clinical allergic reactions
Solution Approach 1:
The patent extracts and removes the harmful solvents (polyoxyethylene castor oil and anhydrous alcohol) from the formulation while retaining the ability to administer paclitaxel through injection. This is achieved by using alternative solvent systems that do not trigger allergic reactions.
Solution Approach 2:
The patent changes the chemical parameters of the solvent system by replacing castor oil and alcohol with alternative solvents having different chemical properties. This parameter change eliminates the allergenicity while maintaining solubility and injectability.
2Quantity of substance
If paclitaxel is formulated with high cyclodextrin proportions to improve solubility, then water solubility increases, but the formulation complexity and cost increase
Solution Approach 1:
The patent optimizes the cyclodextrin-to-paclitaxel ratio parameter to achieve maximum solubility enhancement with minimum cyclodextrin concentration. This parameter optimization reduces formulation complexity while maintaining high water solubility.
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 resulting composition exhibits enhanced solubility of paclitaxel up to 10 mg/ml, improved stability, reduced side effects, and lower cyclodextrin proportions, making it suitable for clinical use with minimal residual organic solvents and improved safety.
Implementation Method 1
a pharmaceutical composition comprising paclitaxel and hydroxypropyl-sulfobutyl-β-cyclodextrin or sulfobutyl-β-cyclodextrin... the inclusion complex is prepared
Implementation Method 2
dissolving paclitaxel in an aqueous solution of the cyclodextrin
Implementation Method 3
removing ethanol under reduced pressure to achieve a stable and highly soluble paclitaxel/cyclodextrin inclusion with low residual organic solvents
Data Source
AI summary
A pharmaceutical composition comprising cyclodextrin/paclitaxel inclusion, which consists of paclitaxel, cyclodextrin and a pharmaceutically acceptable excipient, wherein the mass ratio of the paclitaxel to cyclodextrin is 1:10-150, the said cyclodextrin is hydroxylpropyl-sulfobutyl-7-β-cyclodextrin, or sulfobutylether-7-β-cyclodextrin, or their mixture; the stability constant of the cyclodextrin/paclitaxel inclusion is Ka=5396M−1−1412M−1. The preparation method of the pharmaceutical composition is as follow: (a) A solution of cyclodextrin is added dropwise to a solution of paclitaxel in ethanol. (b) The resulting mixture is filtered through microporous membrane of 0.2-0.4 μm after being dissolved. (c) Ethanol is removed under reduced pressure to give a liquid inclusion which has the ethanol level of less than 2%, or alternatively water is also removed under reduced pressure, the resulting product is dried giving a solid inclusion.