Labdane Diterpene Thermoformed Extrudate for Aqueous Solubility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current formulations of labdane diterpenes, such as andrographolide, face challenges due to low solubility in aqueous phases and bioavailability, necessitating complex and restrictive manufacturing methods that often involve organic solvents, limiting their therapeutic effectiveness.
Innovation Solution
A thermoformed extrudate composition comprising labdane diterpenes combined with natural or synthetic polymers like amino acids, peptides, proteins, or oligosaccharides, achieved through hot melt extrusion, which increases solubility and bioavailability while being easier and more economical to produce.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If labdane diterpenes are formulated using current methods (extrusion/spheronisation or Tween screw granulation), then particles or granules can be produced, but the solubility in aqueous phase remains too low and bioavailability is poor
Solution Approach 1:
The patent uses cyclodextrins as intermediary molecules that form inclusion complexes with labdane diterpenes. The cyclodextrin cavity accommodates the hydrophobic diterpene molecule, while the hydrophilic outer surface of cyclodextrin enables solubility in aqueous media, thereby mediating between the incompatible requirements of maintaining diterpene structure and achieving aqueous solubility
Solution Approach 2:
The patent modifies the physical-chemical parameters of labdane diterpenes by forming molecular complexes with cyclodextrins. This changes the solubility parameter from extremely low (practically insoluble) to sufficiently high for therapeutic use, while maintaining the pharmacologically active diterpene structure intact
2Reliability
If labdane diterpene-cyclodextrin complexes are formed to increase solubility, then bioavailability improves, but the manufacturing method becomes particularly restrictive and requires organic solvents
Solution Approach 1:
The patent extracts and eliminates the problematic step of using organic solvents from the manufacturing process. By employing direct co-precipitation or freeze-drying methods where cyclodextrin and diterpene are mixed in aqueous or alcoholic solutions that are then evaporated or frozen, the method removes the need for separate organic solvent solubilization steps, simplifying the overall manufacturing process
Solution Approach 2:
The patent enables the system to self-assemble into the desired complex form through spontaneous inclusion complex formation when cyclodextrin and labdane diterpene are brought together in appropriate conditions. This self-organization eliminates the need for complex controlled synthesis procedures, allowing simple mixing followed by solvent removal to yield the active complex
3Quantity of substance
If organic solvents are used to solubilise labdane diterpenes before complex formation, then the diterpene can be dissolved, but the process becomes more complex involving evaporation and filtration steps
Solution Approach 1:
The patent merges the solubilization function and complex formation function into a single integrated step. By using cyclodextrin-containing aqueous or alcoholic solutions directly as the dissolution medium, the diterpene dissolves and forms the inclusion complex simultaneously, eliminating separate solubilization and complexation steps that would otherwise require multiple unit operations
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 exhibits significantly enhanced solubility and bioavailability of labdane diterpenes, maintaining stability over time and facilitating their therapeutic properties, particularly in aqueous environments like the intestinal medium.
Implementation Method 1
hot melt extrusion, which increases solubility and bioavailability
Implementation Method 2
achieved through hot melt extrusion
Data Source
AI summary
The present invention relates to a composition in the form of a thermoformed extrudate comprising at least one labdane diterpene (also called labdane), and at least one natural or synthetic polymer selected from the group made up of amino acids, natural or synthetic peptides and polypeptides, natural or synthetic proteins, natural or synthetic oligosaccharides, natural or synthetic non-cellulose polysaccharides, derivatives thereof and mixtures thereof.