Membrane-adherent self-assembled systems for treatment of ocular disorders
Inventors
Barman, Shikha P. • Ward, Kevin L. • Cromwick, Anne-Marie • Barman, Koushik • Thekkedath, Ritesh V.
Assignees
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Publication Number
US-10603273-B2
Publication Date
2020-03-31
Expiration Date
Abstract
A liquid crystalline drug delivery system for ocular administration. The drug delivery system, which is mucoadhesive, biocompatible, non-irritating, and tissue permeable, contains nanoparticles stably dispersed in an aqueous solution and can be formulated for sustained release. Also provided are methods for producing the drug delivery system and methods for treating ocular disorders by administering it to a subject.
Core Innovation
The invention relates to a mucoadhesive, biocompatible liquid crystalline drug delivery system for ocular administration. The system includes nanoparticles dispersed in an aqueous solution, where the nanoparticles include a lipidic component and the aqueous solution contains a mucoadhesive hydrophilic polymer and a buffer. The nanoparticles have a size of 40 nm to 900 nm, and the liquid crystalline system provides sustained release and improved bioavailability, including improved corneal permeability compared with suspensions and reference formulations.
The disclosed system addresses the need for improved corneal permeability and bioavailability in ocular drug delivery while also benefiting from mucoadhesion and sustained release. It combines a lipidic component with a mucoadhesive hydrophilic polymer in an aqueous buffer and forms a liquid crystalline drug delivery system from a combined nano/micro-dispersion. The system is described with controlled formulation temperatures and a weight ratio between the first solution and the second solution of 1:1 to 1:15.
The production method forms a first solution containing an API and a lipidic component, obtains a second aqueous solution including a mucoadhesive hydrophilic polymer and a buffer, and mixes the two solutions by ultrasonication, high shear homogenization, high shear mixing, high pressure homogenization, or a combination thereof to form a combined nano/micro-dispersion. The nano/micro-dispersion is then cooled to form the liquid crystalline drug delivery system. The document also specifies blepharitis and glaucoma formulations with defined excipients and physicochemical parameters.
Claims Coverage
The document includes four independent claim sets that cover four inventive features: a method of producing a liquid crystalline drug delivery system, the liquid crystalline drug delivery system as a composition, a blepharitis-specific liquid crystalline formulation, and glaucoma/posterior-segment disease formulations.
Liquid crystalline drug delivery system production by two-solution mixing and controlled cooling
forming a first solution containing an API and a lipidic component; obtaining a second solution including a mucoadhesive hydrophilic polymer and a buffer; mixing the first and second solutions to form a combined nano/micro-dispersion; and cooling the nano/micro-dispersion to form a liquid crystalline drug delivery system, with a weight ratio between the first solution and the second solution of 1:1 to 1:15.
Liquid crystalline drug delivery system with specified nanoparticle size and mucoadhesive aqueous phase
nanoparticles dispersed in an aqueous solution, the nanoparticles including a lipidic component, the aqueous solution containing a mucoadhesive hydrophilic polymer and a buffer, and the nanoparticles having a size of 40 nm to 900 nm.
Blepharitis treating liquid crystalline drug delivery system with quantified composition and physicochemical parameters
a liquid crystalline drug delivery system for treating blepharitis comprising fluticasone propionate or fluticasone furoate, medium chain triglycerides, castor oil, PEG-stearate, cetyl alcohol, tyloxapol, poloxamer 407, PEG-400, monosodium phosphate, disodium phosphate, tween 80, and a mucoadhesive polymer, wherein the system has a pH of 6-7.5, an osmolality of 250-340 mOsm/kg, and a viscosity of 200-1000 cP.
Liquid crystalline dispersion for treating glaucoma with specified excipient composition and physicochemical parameters
a liquid crystalline dispersion for treating glaucoma comprising an anti-glaucoma drug, a mucoadhesive polymer, medium chain triglycerides, castor oil, PEG-stearate, cetyl alcohol, tyloxapol, poloxamer 407, PEG-400, monosodium phosphate, disodium phosphate, and tween 80, wherein the dispersion has a pH of 6-7.5, an osmolality of 250-340 mOsm/kg, and a viscosity of 200-1000 cP.
Overall, the claims cover production of a liquid crystalline drug delivery system by mixing an API/lipidic first solution with an aqueous mucoadhesive polymer/buffer second solution and cooling to form the liquid crystalline system, the composition itself as nanoparticles in a mucoadhesive aqueous buffered phase with defined size, and specific ocular disease-targeted formulations for blepharitis and glaucoma.
Stated Advantages
Improved corneal permeability compared with suspensions and commercial reference formulations.
Improved bioavailability.
Sustained release.
Extended dispersion stability (no settling) for 90 days.
Documented Applications
Treating blepharitis by administering a liquid crystalline drug delivery system to the eye.
Treating glaucoma by administering a liquid crystalline dispersion to a subject’s eye.
Treating a posterior segment ocular disease with an injectable composition including a liquid crystalline dispersion.
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