Method for improving aqueous solubility of water-insoluble or slightly water-soluble drugs
Inventors
Grassauer, Andreas • Prieschl-Grassauer, Eva • Bodenteich, Angelika • MOROKUTTI-KURZ, Martina • Nakowitsch, Sabine • KAINTZ, Cornelia
Assignees
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Publication Number
US-11510859-B2
Publication Date
2022-11-29
Expiration Date
Abstract
A method of increasing the solubility of a water-insoluble or slightly water-soluble hydrophobic organic compound in an aqueous solvent includes adding a saponin component selected from escin, glycyrrhizin, and Quillaya saponaria extract to the aqueous solvent in an amount sufficient to trigger the formation of micelles, wherein in a first step the hydrophobic organic compound is pre-dissolved in an organic solvent, and in a second step the organic solvent comprising the pre-dissolved compound is admixed to the aqueous solvent, whereby at least a part of the insoluble or slightly soluble hydrophobic organic compound gets solubilized and dissolved in the aqueous solvent, yielding an aqueous composition having an increased concentration of said organic compound dissolved therein. Also indicated are pharmaceutical or cosmetic compositions including a water-insoluble or slightly water-soluble organic compound dissolved in an aqueous solvent at substantially increased concentrations.
Core Innovation
The invention relates to a pharmaceutical or cosmetic composition comprising a water-insoluble or slightly water-soluble hydrophobic organic compound dissolved in an aqueous solvent system. The hydrophobic organic compound is selected from budesonide, tacrolimus and fluticasone, and at least part of the compound is dissolved through solubilization by way of attachment to micelles present in the aqueous solvent system.
The aqueous solvent system comprises a saponin component comprising escin at or above a critical micelle escin concentration, with the concentration of escin in the aqueous solvent system in a range of from 0.01% to 0.1% w/v. The aqueous solvent system further comprises a McIlvaine buffer having a pH of 6, propylene glycol at a concentration of from 5–10%, and dexpanthenol at a concentration of from 1% to 5%.
The invention addresses the low aqueous solubility of water-insoluble or slightly water-soluble hydrophobic organic compounds, including budesonide, fluticasone propionate and tacrolimus, and the related need for improved solubilization and dissolution in an aqueous solvent system. The disclosed compositions are compatible with aqueous delivery and can be provided with optional co-excipients such as carrageenans and hyaluronic acid, and can be prepared in formats that support mucosal delivery.
Claims Coverage
The relevant independent claim is directed to a pharmaceutical or cosmetic composition in which selected hydrophobic organic compounds are dissolved in an aqueous solvent system by solubilization through attachment to micelles formed by a saponin component, specifically with escin at or above a critical micelle concentration and with defined buffer, solvent, and stabilizing components. This claim requires a micelle-mediated dissolution mechanism and a specific solvent system composition, including McIlvaine buffer at pH 6, propylene glycol, and dexpanthenol, together with an escin concentration range.
Micelle-mediated solubilization in an aqueous solvent system
A pharmaceutical or cosmetic composition wherein a water-insoluble or slightly water-insoluble hydrophobic organic compound is dissolved in an aqueous solvent system, and at least part of the compound is dissolved through solubilization by attachment to micelles present in the aqueous solvent system.
Escin at or above critical micelle concentration
The aqueous solvent system comprises a saponin component comprising escin at or above a critical micelle escin concentration, wherein the concentration of escin is from 0.01% to 0.1% w/v.
Defined aqueous solvent system components (McIlvaine pH 6, propylene glycol, dexpanthenol)
The aqueous solvent system comprises a McIlvaine buffer having a pH of 6, propylene glycol at a concentration of from 5–10%, and dexpanthenol at a concentration of from 1% to 5%.
Selected hydrophobic organic compounds (budesonide, tacrolimus, fluticasone)
The water-insoluble or slightly water-soluble hydrophobic organic compound is selected from the group consisting of budesonide, tacrolimus and fluticasone.
Across the independent claim, the inventive coverage centers on dissolving selected hydrophobic compounds in an aqueous solvent system by solubilization via attachment to micelles generated by an escin saponin component at or above its critical micelle concentration, with the aqueous system specified to include a McIlvaine buffer at pH 6, propylene glycol, and dexpanthenol in defined concentration ranges.
Stated Advantages
Improved solubilization/dissolution of water-insoluble or slightly water-soluble hydrophobic organic compounds in an aqueous solvent system via micelle-mediated attachment.
Storage stability of dissolved drugs is addressed in the disclosed examples.
Mucosal penetration and in vivo TNF-α reduction are documented.
Documented Applications
Mucosal delivery, including nasal mucosa penetration, and delivery in formats compatible with mucosal tissues (nasal, eye) are documented.
In vivo evaluation is documented for reduction of TNF-α in an LPS-induced acute lung inflammation context.
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