Relating to antiviral compositions
Inventors
Foster, Alison J. • Long, James • Rannard, Steven P. • Wang, Dong • Duncalf, David J.
Assignees
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Publication Number
US-9192584-B2
Publication Date
2015-11-24
Expiration Date
Abstract
The present invention provides a composition and an antiviral drug preparation, each comprising at least one water-insoluble antiviral drug and at least one water-soluble carrier material, wherein the water-insoluble antiviral drug is dispersed through the water-soluble carrier material in nano-disperse form. The present invention further provides processes for preparing the compositions and drug preparations, and also aqueous nano-dispersions obtained by combining water and the compositions.
Core Innovation
The invention relates to a substantially solvent-free composition comprising at least one water-insoluble antiviral drug and at least one water-soluble carrier material, where the water-insoluble antiviral drug is dispersed through the water-soluble carrier material in nano-disperse form. The water-soluble carrier material is a water-soluble polymer selected from polyvinylalcohol, polyethylene glycol, polyvinylpyrrolidone, poly(2-ethyl-2-oxazaline), hydroxypropylcellulose, hydroxypropylmethylcellulose, alginates, and mixtures thereof. The nano-disperse form is described by a z-average particle size below 1000 nm.
A process is described for preparing the substantially solvent-free composition by forming an emulsion comprising a solution of the water-insoluble antiviral drug in a water-immiscible solvent and a solution of the water-soluble carrier material in an aqueous solvent. The emulsion or a single phase solution is then spray-dried or freeze-dried to remove the aqueous solvent and the water-immiscible solvent. The result is the substantially solvent-free composition comprising a nano-dispersion of the antiviral drug in the carrier material.
The background problem addressed is that water-insoluble antiviral drugs are difficult to disperse and may have pharmacokinetic limitations, and that aqueous dispersion and improved pharmacokinetic metrics are desired. The document further describes rapid aqueous dispersion, potential water-clear dispersions, and potential pharmacokinetic improvements such as increased AUC and Cmax, earlier Cmax, longer half-life, and reduced fed/fasted variability.
Claims Coverage
The relevant independent claim defines a process for preparing a substantially solvent-free nano-dispersion composition by forming an emulsion of a water-insoluble antiviral in a water-immiscible solvent with a water-soluble polymer in aqueous solvent, followed by spray-drying or freeze-drying to remove solvents. The independent claim centers on the substantially solvent-free nano-dispersion in a water-soluble polymer matrix and the emulsion/drying process for achieving it.
Substantially solvent-free nano-dispersion antiviral composition in a water-soluble polymer carrier
A substantially solvent-free composition comprising at least one water-insoluble antiviral drug and at least one water-soluble carrier material, where the water-insoluble antiviral drug is dispersed through the water-soluble carrier material in nano-disperse form.
Emulsion formation with water-immiscible solvent drug phase and aqueous polymer phase
The process forms an emulsion comprising a solution of the water-insoluble antiviral drug in a water-immiscible solvent and a solution of the water-soluble carrier material in an aqueous solvent.
Spray-drying or freeze-drying to remove solvents and yield the nano-dispersion
The process spray-drying or freeze-drying the emulsion or single phase solution to remove the aqueous solvent and the water-immiscible solvent to obtain the substantially solvent-free composition comprising a nano-dispersion of the antiviral drug in the carrier material.
Nano-dispersion particle size threshold by z-average
The nano-disperse form is characterized by a z-average particle size below 1000 nm.
Selected water-insoluble antiviral classes and pharmaceutically acceptable salts
The water-insoluble antiviral drug is selected from protease inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and pharmaceutically-acceptable salts or mixtures thereof.
Water-soluble carrier materials including optional inorganic, surfactant, or sugar components
The water-soluble carrier material additionally includes a component selected from inorganic materials, water-soluble surfactants, water-soluble sugars, or mixtures thereof.
Across the independent claim and its refinements, the document focuses on forming a substantially solvent-free nano-dispersion of a water-insoluble antiviral drug in a water-soluble polymer carrier, using an emulsion with a drug solution in a specified water-immiscible solvent and a polymer solution in aqueous solvent, then spray-drying or freeze-drying to remove solvents.
Stated Advantages
Rapid aqueous dispersion.
Potential water-clear dispersions.
Improved pharmacokinetic metrics including increased AUC and Cmax.
Earlier Cmax.
Longer half-life.
Reduced fed/fasted variability.
Documented Applications
Antiviral (including antiretroviral) nano-dispersions intended to support aqueous dispersion and improved pharmacokinetic and intestinal permeation behavior, including Caco-2 intestinal permeation comparisons.
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