Oligosaccharide Stabilized Kappa Opioid Agonist Formulations
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Solution Overview
Problem
Kappa opioid receptor agonists require new formulations for efficient delivery and bioavailability due to their unique physicochemical properties, and existing formulations face stability issues during storage and interaction of components, leading to unpredictable bioavailability.
Innovation Solution
A formulation combining a kappa opioid receptor agonist with an oligosaccharide stabilizing agent, such as trehalose, for oral delivery, which includes coating or embedding the agonist in particles with absorption enhancers and enteric coatings to maintain stability and enhance bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If kappa opioid receptor agonists are formulated for oral delivery, then bioavailability is improved, but stability during storage deteriorates
Solution Approach 1:
The patent introduces oligosaccharides (such as trehalose, sucrose, lactose, or maltose) as intermediary substances that mediate between the kappa opioid receptor agonist and the storage environment. These oligosaccharides form a protective matrix that stabilizes the peptide agonist during storage while allowing for effective oral delivery and absorption in the gastrointestinal tract, thus resolving the contradiction between storage stability and bioavailability.
Solution Approach 2:
The formulation creates a composite material system consisting of the kappa opioid receptor agonist embedded within or combined with oligosaccharides. This composite structure provides both the stability needed for long-term storage and the bioavailability required for oral delivery, as the oligosaccharide matrix protects the peptide from degradation while maintaining its pharmacological activity.
2Reliability
If formulation components are combined to enhance delivery, then bioavailability is improved, but component interaction leading to instability increases
Solution Approach 1:
The patent utilizes the specific physicochemical properties of oligosaccharides, particularly their ability to form hydrogen bonds and create a protective amorphous matrix. By selecting oligosaccharides with specific molecular structures (such as trehalose with its unique alpha,alpha-1,1-glycosidic linkage), the formulation changes the physical state and interaction parameters between components, reducing unwanted interactions while maintaining stability and enhancing oral bioavailability of the kappa opioid receptor agonist.
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 formulation achieves stability over extended periods and optimized bioavailability, ensuring effective prophylaxis, inhibition, or treatment of kappa opioid receptor-associated diseases by maintaining the kappa opioid receptor agonist's stability and enhancing its absorption in the gastrointestinal system.
Implementation Method 1
the stabilizing agent renders the API in the formulation stable to storage over extended periods of time
Implementation Method 2
may also include an enteric coating to provide for protection of the formulation in acidic conditions and dissolution of the formulation under intestinal physiological conditions
Implementation Method 3
the formulation of the invention includes a kappa opioid receptor agonist and a stabilizing agent, such as an oligosaccharide, and an absorption enhancer
Data Source
AI summary
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist, an oligosaccharide stabilizing agent and an optional absorption enhancer. The kappa opioid receptor agonist may be coated with, embedded in or mixed with an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists, the oligosaccharide and the absorption enhancer of the invention. The invention further provides methods of manufacture of the formulations and methods of their use for the prophylaxis, inhibition and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation. The methods of use include administering to the mammal the formulation of the kappa opioid receptor agonist, oligosaccharide and optional absorption enhancers.