Biphasic Excipient Composition for Hydrophobic Drug Bioavailability
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Solution Overview
Problem
Bioactive agents with high octanol-water partition coefficients exhibit poor oral bioavailability and pharmacokinetics due to aggregation in lipid phases and hepatic-portal circulation, leading to inefficient absorption and metabolism.
Innovation Solution
Formulating bioactive agents in biphasic compositions with a high surface-area-to-volume ratio solid phase and specific excipients that dissolve in the buccal cavity, allowing for partitioning into the gastrointestinal epithelium and bypassing hepatic-portal circulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hydrophobic bioactive agents are administered orally, then they can be delivered to the body, but they aggregate in lipid phases and have poor oral bioavailability
Solution Approach 1:
The invention divides the single-phase system into a biphasic composition with distinct hydrophobic and hydrophilic phases. The hydrophobic bioactive agent is dispersed in the hydrophobic phase with high surface area, while the hydrophilic phase contains water-soluble excipients. This segmentation prevents aggregation by maintaining phase separation and providing a hydrophilic pathway for absorption.
Solution Approach 2:
The invention changes the physical parameters of the composition by creating a biphasic system with specific phase ratios and surface area characteristics. The hydrophobic phase is formulated with high surface area-to-volume ratio to increase dissolution rate, while the hydrophilic phase is optimized for water solubility. These parameter changes enable the hydrophobic agent to dissolve rapidly and partition into the hydrophilic phase for absorption.
2Productivity
If hydrophobic agents partition into lipid phase in the gastrointestinal tract, then they can be released from the composition, but they are excreted rather than absorbed
Solution Approach 1:
The hydrophilic phase acts as an intermediary between the hydrophobic bioactive agent and the aqueous gastrointestinal environment. The water-soluble excipients in the hydrophilic phase facilitate dissolution and create a hydrophilic medium that enables the hydrophobic agent to partition into the gastrointestinal epithelium rather than remaining in lipid phases where it would be excreted.
Solution Approach 2:
The invention changes the solubility parameters by formulating a hydrophilic phase with water-soluble excipients that creates a favorable partitioning environment. This parameter change enables the hydrophobic agent to transition from a lipid-phase-bound state to a hydrophilic-dissolved state, facilitating absorption into the gastrointestinal epithelium and preventing excretion.
3Reliability
If excipients are used to disperse hydrophobic agents in biphasic compositions, then dissolution and absorption are enhanced, but the formulation complexity increases
Solution Approach 1:
The hydrophilic phase serves multiple functions simultaneously: it provides a water-soluble medium for dissolution, acts as a vehicle for the hydrophobic agent, facilitates partitioning into the gastrointestinal epithelium, and enables bypassing of hepatic-portal circulation. This multi-functionality reduces the need for additional separate components, thereby managing formulation complexity while achieving improved bioavailability.
Solution Approach 2:
The hydrophilic phase with water-soluble excipients serves as an intermediary that simplifies the overall formulation by providing a single hydrophilic vehicle that handles dissolution, transport, and absorption facilitation. This intermediary approach avoids the need for multiple separate excipients or complex delivery systems, managing formulation complexity while achieving the desired bioavailability enhancement.
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
Improves oral bioavailability and pharmacokinetics by enhancing dissolution and absorption of hydrophobic agents directly into the gastrointestinal tract, thereby increasing their systemic availability.
Implementation Method 1
excipients that readily dissolve in water
Implementation Method 2
the dissolution of the excipients results in the partitioning of the hydrophobic agents into the gastrointestinal epithelium
Implementation Method 3
the solid phase has a surface-area-to-volume ratio that is greater than 500 per meter, and the composition comprises the solid phase at a greater concentration by mass than the liquid phase. Without limiting this disclosure or any claim that matures from this patent document, increasing the surface area of the solid phase increases the surface area of the liquid phase, which accelerates dissolution of the composition following consumption
Data Source
AI summary
Various aspects of this disclosure relate to excipients that comprise a solid phase and a liquid phase, wherein the solid phase has a surface-area-to-volume ratio of at least 500 per meter. In various embodiments, the liquid phase comprises an active ingredient, and the liquid phase coats substantially all of the solid phase, which increases the surface area of the liquid phase and thereby improves the bioavailability and pharmacokinetics of the active ingredient.