N-Acyl-Ethanolamine Solubility via Cyclodextrin Inclusion
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Solution Overview
Problem
N-acyl-ethanolamines, such as palmitoylethanolamine, are not water-soluble due to their hydrophobic nature, making it difficult to formulate ophthalmic, intra-articular, or intravesical solutions, as previous attempts with lipophilic means and cyclodextrin inclusion complexes resulted in insoluble or poorly soluble derivatives.
Innovation Solution
A water-soluble pharmaceutical composition is achieved by forming an inclusion complex of N-acyl-ethanolamines with methyl-beta-cyclodextrin and incorporating a polymeric emulsifier like polyvinyl alcohol, which stabilizes the solution at various temperatures, even with reduced cyclodextrin excess.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If N-acyl-ethanolamines are used in pharmaceutical compositions, then therapeutic effects are achieved, but water solubility is poor due to hydrophobic nature
Solution Approach 1:
The patent uses cyclodextrins as intermediary molecules to solubilize N-acyl-ethanolamines. The cyclodextrin forms an inclusion complex where the hydrophobic N-acyl-ethanolamine is encapsulated within the cyclodextrin cavity, while the external surface of cyclodextrin remains hydrophilic, enabling water solubility without compromising the therapeutic agent's efficacy.
Solution Approach 2:
The patent creates a composite pharmaceutical composition combining cyclodextrin and N-acyl-ethanolamine in a specific ratio. This composite inclusion complex combines the hydrophobic therapeutic molecule with the hydrophilic cyclodextrin carrier, achieving both solubility and therapeutic effectiveness simultaneously.
2Ease of operation
If lipophilic means are used to solubilize N-acyl-ethanolamines, then solubility is improved, but the formulation becomes unsuitable for ophthalmic and intra-articular use
Solution Approach 1:
The patent changes the solubility parameter from lipophilic to hydrophilic by using cyclodextrin inclusion complexes. This parameter change enables the formulation to be compatible with ophthalmic and intra-articular applications while maintaining adequate solubility through the cyclodextrin-water interaction.
3Ease of manufacture
If alpha-, beta-, or gamma-cyclodextrins are used for solubilization, then inclusion complex formation occurs, but the derivatives remain insoluble or poorly soluble
Solution Approach 1:
The patent applies local quality modification by using hydroxypropyl-beta-cyclodextrin, which has modified hydrophilic groups on the cyclodextrin ring. This local modification of the cyclodextrin structure enhances the overall water solubility of the inclusion complex while maintaining the inclusion capability.
Data Source
AI summary
It is the object of the present invention a composition containing an N-acyl-ethanolamine in a solubilized form, particularly a solution for ophthalmic, intra-articular or intravesical use. Particularly, the present invention relates to a water-soluble composition comprising one or more N-acylethanolamines (NAE) in the form of an inclusion complex in methyl-beta-cyclodextrin (MβCD).