Amorphous Intranasal Powder for Bioavailability
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Solution Overview
Problem
Current intranasal pharmaceutical compositions with crystalline active agents have limited bioavailability due to low solubility and poor pharmacokinetic parameters when administered intranasally.
Innovation Solution
Development of an intranasal pharmaceutical powder composition comprising amorphous active agents with a thickening agent, carrier, and sugar alcohol, where at least 20% of the active agent is amorphous, with an average particle size of 10-300 microns, enhancing bioavailability by improving pharmacokinetic parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If crystalline active agents are used in intranasal pharmaceutical compositions, then the composition has good physical stability, but the bioavailability and pharmacokinetic parameters are limited due to low solubility
Solution Approach 1:
The patent applies parameter changes by transforming the active agent from crystalline form to amorphous form, which fundamentally alters the physical state and solubility characteristics. This phase transition enables significantly improved bioavailability and pharmacokinetic parameters while maintaining composition stability through controlled formulation conditions
Solution Approach 2:
The patent employs composite materials by combining amorphous active agents with specific excipients including thickening agents (carboxymethylcellulose, hydroxypropylmethylcellulose), carriers (mannitol, microcrystalline cellulose), and pH adjusting agents. This composite formulation approach maintains physical stability while enabling the amorphous state to provide enhanced bioavailability
2Reliability
If amorphous active agents are used in intranasal pharmaceutical compositions, then the bioavailability and absorption rate improve, but the manufacturing complexity increases
Solution Approach 1:
The patent utilizes phase transitions by employing freeze-drying technology to transform the active agent from crystalline to amorphous form during manufacturing. This controlled phase transition occurs during the freezing and sublimation process, creating the desired amorphous state without requiring complex post-processing or specialized equipment beyond standard freeze-dryers
Solution Approach 2:
The patent applies preliminary action by pre-formulating the active agent with excipients in a specific composition before the freeze-drying process. The formulation is designed in advance to ensure proper amorphous formation and stability, with excipients selected to facilitate the phase transition and maintain the amorphous state during storage
3Speed
If amorphous active agents are used in intranasal pharmaceutical compositions, then the absorption speed increases, but the particle size control becomes more challenging
Solution Approach 1:
The patent applies parameter changes by controlling the freezing rate and temperature during freeze-drying to achieve the desired particle size range (10-300 microns). By adjusting these thermal parameters, the formulation maintains amorphous structure while achieving optimal particle size for rapid nasal absorption
Solution Approach 2:
The patent employs composite materials with specific excipients that influence particle formation during freeze-drying. Mannitol and microcrystalline cellulose serve as structural components that control particle size and morphology, while carboxymethylcellulose and hydroxypropylmethylcellulose provide viscosity control to prevent aggregation, ensuring particles remain within the 10-300 micron range for optimal absorption
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 achieves a significant improvement in pharmacokinetic parameters, including increased relative bioavailability and faster absorption, compared to crystalline forms, with improved stability and retention of the active agent.
Implementation Method 1
at least about 20 percent by weight of the active agent in the particles is amorphous as determined by X-ray diffraction; when the active agent has a crystalline form, a solubility of the active agent in a crystalline form in an aqueous liquid ranges from about 0.1 μg/mL to about 1 mg/mL
Implementation Method 2
particles that comprise an active agent and at least one member selected from the group consisting of a thickening agent, a carrier, a pH adjusting agent, a sugar alcohol
Implementation Method 3
particles that comprise an active agent and at least one member selected from the group consisting of a thickening agent, a carrier, a pH adjusting agent, a sugar alcohol
Data Source
AI summary
Disclosed herein are pharmaceutical powder compositions, methods of making such compositions, and uses thereof.