Cyclodextrin-Stabilized Beta-Blocker Solutions for Parenteral Use
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Ultrashort-effective β-adrenoreceptor antagonists like esmolol and landiolol have low stability in aqueous solutions and are often hypertonic, posing risks in intensive care medicine, with existing solutions requiring additional stabilizers and time-consuming preparation.
Innovation Solution
Incorporating cyclodextrin and/or functional cyclodextrin derivatives into the solutions to enhance stability and osmolarity, allowing for isotonic, storage-stable formulations suitable for parenteral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If ultrashort-effective β-adrenoreceptor antagonists are formulated in aqueous solutions for parenteral administration, then they can be administered intravenously, but the active substances are hydrolytically split into free acids and alcohol, leading to low stability
Solution Approach 1:
Cyclodextrins are used as intermediary substances that form inclusion complexes with ultrashort-effective β-adrenoreceptor antagonists. The cyclodextrin cavity encapsulates the hydrophobic part of the active substance, protecting it from hydrolysis while maintaining solubility in aqueous solutions. This resolves the contradiction by providing both intravenous readiness and enhanced stability through the mediating cyclodextrin molecule.
Solution Approach 2:
The invention creates a composite pharmaceutical formulation consisting of cyclodextrins combined with ultrashort-effective β-adrenoreceptor antagonists. This composite system leverages the hydrophilic exterior of cyclodextrins for aqueous solubility and the hydrophobic interior cavity for stabilizing the active substance, thereby achieving both ease of administration and improved stability simultaneously.
2Quantity of substance
If the active substance concentration is increased for effective administration, then therapeutic efficacy is improved, but the solutions become hypertonic, posing risks in intensive care medicine
Solution Approach 1:
The invention changes the physical-chemical parameters of the formulation by introducing cyclodextrins, which alter the osmotic properties of the solution. The cyclodextrin-active substance complex modifies the solution's tonicity, allowing higher active substance concentrations to be achieved without creating harmful hypertonic effects. This parameter change enables both effective therapeutic concentrations and vascular safety.
3Stability of the object's composition
If alcohol is added in concentrations of around 25% to stabilise the solutions, then stability is improved, but additional risks are associated with the use in intensive care medicine
Solution Approach 1:
The invention replaces alcohol-based stabilization with cyclodextrin-based stabilization, fundamentally changing the chemical parameter approach. Instead of using 25% alcohol to prevent hydrolysis, cyclodextrins provide steric protection through inclusion complexation, achieving equal or superior stability without the harmful effects of high alcohol concentrations in clinical settings.
4Stability of the object's composition
If freeze-dried compositions are used to improve stability, then storage stability is enhanced, but time-consuming preparation is required before use
Solution Approach 1:
The invention adopts a ready-to-use liquid formulation containing cyclodextrins that provides sufficient storage stability without requiring freeze-drying. This disposable-ready approach eliminates the need for time-consuming reconstitution procedures while maintaining stability through the cyclodextrin protection mechanism, thus gaining time without sacrificing stability.
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 use of cyclodextrin significantly increases the stability and osmolarity of ultrashort-effective β-adrenoreceptor antagonist solutions, enabling higher concentrations for use as ready-to-use products with reduced degradation and vascular protection.
Implementation Method 1
Cyclodextrins are cyclic oligosaccharides with a hydrophobic inner cavity and a hydrophilic outer surface. The hydrophobic inner cavity of cyclodextrins can accommodate hydrophobic guest molecules, forming inclusion complexes through hydrophobic interactions.
Implementation Method 2
The outer surface of cyclodextrins is covered with hydroxyl groups that can form hydrogen bonds with water molecules, creating a hydrophilic shell that enhances water solubility and modulates osmotic properties.
Data Source
AI summary
The present invention relates to a pharmaceutical composition in the form of a storage-stable solution for the parenteral administration of ultrashort-effective β-adrenoreceptor antagonists, comprising a) an ultrashort-effective β-adrenoreceptor antagonist and/or a pharmaceutically acceptable salt thereof, b) water, and c) a cyclodextrin and/or a functional cyclodextrin derivative. The composition according to the invention has high stability, even without the presence of additional adjuvants.