Membrane-adherent self-assembled system 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-9901544-B2
Publication Date
2018-02-27
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 liquid crystalline drug delivery system comprising nanoparticles dispersed in an aqueous solution, wherein the nanoparticles include a lipidic component and an alcohol. The aqueous solution contains a mucoadhesive hydrophilic polymer and a buffer, and the system is defined by physicochemical ranges including pH of 6-7.5, osmolarity of 250-340 mOsm/L, and viscosity of 200-1000 cP.
The invention also provides a method for producing the liquid crystalline drug delivery system by forming a first solution containing the lipidic component and the alcohol maintained at a temperature of 40-55°C and a second solution including the mucoadhesive hydrophilic polymer and a buffer. The first and second solutions are mixed to form a combined nano/micro-dispersion by a high energy mixing process selected from sonication, high shear mixing, and a combination thereof.
The combined nano/micro-dispersion is subjected to microfluidization at a temperature of <10°C to room temperature to form a nano-dispersion, and the nano-dispersion is incubated at 2-5°C to form a liquid crystalline drug delivery system. The lipidic component includes phosphatidylcholine and medium chain triglycerides, the alcohol is cetyl alcohol, and the mucoadhesive hydrophilic polymer is selected from sodium hyaluronate, xanthan gum, guar gum, carboxymethyl cellulose, 1-4 beta glucan, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), tamarind seed polysaccharide, sodium alginate, polycarbopol, polycarbophil, and a mixture thereof.
Claims Coverage
The partial content includes two independent claims: a method and a liquid crystalline drug delivery system. Across these claims, the inventive features are defined by a specific two-solution formulation strategy with temperature-controlled high energy mixing and microfluidization, followed by cold incubation to form liquid crystalline nanoparticles in a mucoadhesive buffered aqueous system. The claims also impose defined composition selections and physicochemical ranges.
Temperature-controlled two-solution mixing to form a nano/micro-dispersion
Forming a first solution containing a lipidic component and an alcohol maintained at a temperature of 40-55°C; obtaining a second solution including a mucoadhesive hydrophilic polymer and a buffer maintained at a temperature of 5-55°C; and mixing the first solution and the second solution to form a combined nano/micro-dispersion by a high energy mixing process selected from sonication, high shear mixing, and a combination thereof.
Microfluidization and cold incubation to form a liquid crystalline drug delivery system
Subjecting the combined nano/micro-dispersion to microfluidization at a temperature of <10°C to room temperature to form a nano-dispersion and incubating the nano-dispersion at 2-5°C to form a liquid crystalline drug delivery system.
Defined lipidic/alcohol composition and mucoadhesive hydrophilic polymer selection
A weight ratio between the first solution and the second solution of 1:1 to 1:15, wherein the lipidic component includes phosphatidylcholine and medium chain triglycerides, the alcohol is cetyl alcohol, and the mucoadhesive hydrophilic polymer is selected from the group consisting of sodium hyaluronate, xanthan gum, guar gum, carboxymethyl cellulose, 1-4 beta glucan, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), tamarind seed polysaccharide, sodium alginate, polycarbopol, polycarbophil, and a mixture thereof.
Nanoparticles in mucoadhesive buffered aqueous system with specified physicochemical ranges
A liquid crystalline drug delivery system comprising nanoparticles dispersed in an aqueous solution, the nanoparticles including a lipidic component and an alcohol, the aqueous solution containing a mucoadhesive hydrophilic polymer and a buffer, wherein the lipidic component is present at 0.1-1% by weight of the system, the alcohol is present at 0.1-5% by weight of the system, the mucoadhesive hydrophilic polymer is present at 1-5% by weight of the system, the nanoparticles have a size of 40 nm to 900 nm, the system has a pH of 6-7.5, an osmolarity of 250-340 mOsm/L, and a viscosity of 200-1000 cP, the lipidic component includes phosphatidylcholine and medium chain triglycerides, the alcohol is cetyl alcohol, and the mucoadhesive hydrophilic polymer is selected from the group consisting of sodium hyaluronate, xanthan gum, guar gum, carboxymethyl cellulose, 1-4 beta glucan, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), tamarind seed polysaccharide, sodium alginate, polycarbopol, polycarbophil, and a mixture thereof.
Across the independent claims, the claim coverage centers on creating a liquid crystalline drug delivery system with mucoadhesive buffered aqueous conditions. The method claim fixes a temperature-controlled two-solution mixing scheme, followed by microfluidization and incubating at 2-5°C, while the system claim fixes composition selections and ranges for component amounts and key physicochemical properties.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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