Naringenin Solubility via pH Adjustment and Cyclodextrin Coating
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Solution Overview
Problem
Naringenin has low solubility and bioavailability when administered orally, leading to low drug concentrations at target sites, and there is a lack of aerosol inhalation formulations for its effective delivery.
Innovation Solution
A solution formulation for aerosol inhalation of naringenin is prepared by regulating the pH value of the solvent and using hydroxypropyl β-cyclodextrin for coating, which increases solubility and stability, allowing for direct delivery to the respiratory tract via an atomizer, enhancing drug concentration and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional coating approach is used to mix naringenin with hydroxypropyl β-cyclodextrin in aqueous solvent, then the solubilization effect is limited by the solubility of naringenin itself in the solvent
Solution Approach 1:
The patent changes the chemical parameters of the solvent system by adjusting pH to 7.4-7.8 and using specific buffer compositions (phosphate buffer, borate buffer, or citrate buffer) to optimize naringenin solubility and cyclodextrin inclusion compound formation, thereby overcoming the limitation of drug solubility in the solvent
Solution Approach 2:
The patent uses hydroxypropyl β-cyclodextrin as an intermediary substance that forms inclusion compounds with naringenin, enabling the drug to be solubilized in aqueous solutions beyond its inherent solubility limits. The cyclodextrin acts as a mediator that encapsulates the drug molecule and facilitates its dissolution
2Quantity of substance
If naringenin is dissolved into ethanol and then mixed with hydroxypropyl β-cyclodextrin to obtain inclusion compound, then the solubility is improved, but the residue of organic solvent limits the population that can use the preparation
Solution Approach 1:
The patent extracts and removes the organic solvent (ethanol) from the system by using aqueous buffers as the solvent base. The formulation completely eliminates organic solvent residue by using water-based buffer systems (phosphate, borate, or citrate buffers at pH 7.4-7.8) to dissolve both the cyclodextrin and the naringenin-cyclodextrin inclusion compounds
Solution Approach 2:
The patent uses aqueous buffers as an intermediary solvent system that allows dissolution of the naringenin-cyclodextrin inclusion compounds without requiring organic solvents. The buffer serves as a mediating medium that maintains appropriate pH and enables complete aqueous solubility
3Reliability
If oral administration route is used for naringenin, then the drug can be administered, but the bioavailability is only approximately 4% and most drug is concentrated at gastrointestinal tract with small fraction reaching lung
Solution Approach 1:
The patent replaces the oral administration mechanical system with an aerosol inhalation system that delivers drug directly to the respiratory tract. The formulation is designed as a nebulizable solution that can be inhaled, substituting the gastrointestinal absorption pathway with direct pulmonary delivery, thereby dramatically improving bioavailability and target site concentration
4Reliability
If aerosol inhalation is used for naringenin delivery, then the drug directly reaches target sites with quick absorption, but there has not been a solution formulation available in the market
Solution Approach 1:
The patent optimizes the formulation parameters including pH (7.4-7.8), buffer composition, ionic strength, and excipient ratios to create a stable, nebulizable solution suitable for aerosol inhalation. These parameter changes enable the formulation to meet both therapeutic effectiveness and manufacturability requirements
Solution Approach 2:
The patent creates a composite formulation system combining naringenin, hydroxypropyl β-cyclodextrin, buffer salts (phosphate, borate, or citrate), and auxiliary excipients in specific proportions. This composite material system provides both the required pharmacological activity and the physical properties needed for aerosol delivery
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 method significantly increases naringenin concentrations at target sites, providing quick efficacy and filling the market gap with a simple, environmentally friendly, and economically viable preparation process suitable for industrial production.
Implementation Method 1
mixing the drug with hydroxypropyl β-cyclodextrin in an aqueous solvent, wherein the solubilization effect is limited by the solubility of the drug itself in the solvent. It is also reported that the drug is firstly dissolved into ethanol and then mixed with hydroxypropyl β-cyclodextrin to obtain the inclusion compound
Implementation Method 2
The obtained solution formulation for aerosol inhalation is directly inhaled into the respiratory system in the atomized form by using an ultrasonic atomizer or an air-compression-type atomizer
Implementation Method 3
The obtained solution formulation for aerosol inhalation is directly inhaled into the respiratory system in the atomized form
Data Source
AI summary
The present invention discloses a solution formulation for aerosol inhalation of naringenin and preparation method thereof. The formulation is prepared from 1 part by weight of naringenin, 15-30 parts by weight of hydroxypropyl β-cyclodextrin, a buffer-salt solution and an appropriate amount of an excipient. The preparation method includes: preparing a buffer-salt solution of a pH value of 7-8.5 by using the buffer salt, adding the naringenin into the buffer-salt solution, then adding the hydroxypropyl β-cyclodextrin, shaking in a constant-temperature air bath till complete dissolving and coating, adding an appropriate amount of the excipient, filtering, filling and sterilizing. The present invention, by firstly increasing the solubility of the free naringenin in the solvent by adjusting the pH value, and then coating the naringenin with the hydroxypropyl β-cyclodextrin, significantly increases the overall concentration of the naringenin in the solvent.