US20130029919A1 - Two part formulation system for opthalmic delivery - Google Patents

Two part formulation system for opthalmic delivery Download PDF

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Publication number
US20130029919A1
US20130029919A1 US13/557,611 US201213557611A US2013029919A1 US 20130029919 A1 US20130029919 A1 US 20130029919A1 US 201213557611 A US201213557611 A US 201213557611A US 2013029919 A1 US2013029919 A1 US 2013029919A1
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Prior art keywords
active agent
therapeutically active
product
listed
stabilizing
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US13/557,611
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English (en)
Inventor
Anuradha V. Gore
Sai M. SHANKAR
Sukhon Likitlersuang
Chetan P. Pujara
Sesha Neervannan
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Allergan Inc
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Allergan Inc
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Priority to US13/557,611 priority Critical patent/US20130029919A1/en
Assigned to ALLERGAN, INC. reassignment ALLERGAN, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NEERVANNAN, Sesha, PUJARA, CHETAN P., GORE, ANURADHA V., LIKITLERSUANG, SUKHON, SHANKAR, SAI
Publication of US20130029919A1 publication Critical patent/US20130029919A1/en
Priority to US15/135,925 priority patent/US9616017B2/en
Priority to US15/483,162 priority patent/US10314887B2/en
Priority to US16/436,200 priority patent/US20190290722A1/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/417—Imidazole-alkylamines, e.g. histamine, phentolamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/559—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing hetero atoms other than oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents

Definitions

  • Embodiments include ophthalmic, otic and intranasal products and methods.
  • labile therapeutically active agents For labile therapeutically active agents, traditional formulation development would include use of stabilizers and/or selection of pH range to optimize stability of the therapeutically active agents. However, high concentrations of stabilizers or selection of product pH that is outside physiological range may lead to safety and tolerability concerns for the product.
  • Some pharmaceutical products intended for ophthalmic, otic and intranasal delivery may be stabilized by making an ophthalmically acceptable liquid by reconstitution prior to dose delivery. This may be an advantage for chemically labile therapeutically active agents which may have a limited shelf life in a formulation suitable for ophthalmic delivery due to their rapid degradation rates.
  • Some embodiments include an ophthalmic pharmaceutical product comprising: a stabilizing composition comprising a therapeutically active agent; a liquid vehicle composition; a removable barrier; wherein the barrier is configured to prevent contact between the stabilizing composition and the liquid vehicle composition; and wherein the product is configured to allow removal of the barrier; wherein the product is configured so that removal of the barrier allows mixing of the stabilizing composition and the vehicle composition to provide a sterile ophthalmically acceptable liquid; wherein the ophthalmically acceptable liquid comprises a therapeutic amount of the therapeutically active agent.
  • Some embodiments include a method of stabilizing a therapeutically active agent for use in an ophthalmically acceptable liquid comprising: providing a stabilizing system comprising: a stabilizing composition comprising the therapeutically active agent; a vehicle composition comprising at least one of: a solublilizer, a surfactant, an osmolality agent, a buffer, and a preservative; and a removable barrier separating the stabilizing composition from the vehicle composition; wherein the system is configured so that removal of the barrier allows mixing between the stabilizing system and the vehicle to provide a sterile ophthalmically acceptable liquid; and wherein the ophthalmically acceptable liquid comprises about 0.0001% to about 5% therapeutically active agent by weight.
  • Some embodiments may include a two part formulation product, which can be reconstituted by mixing the two parts.
  • a stabilizing composition contains a therapeutically active agent in a formulation matrix that may improve the stability or shelf-life of the therapeutically active agent in the formulation matrix.
  • the product also comprises a liquid vehicle composition.
  • the stabilizing composition is separated from the liquid vehicle composition by a removable barrier. Removal of the barrier may allow the two parts to be mixed, so that they may form an ophthalmically acceptable liquid. This may allow the ophthalmically acceptable liquid to have a long enough shelf-life.
  • the removable barrier may have any of a variety of structural features as long as it can separate a stabilizing composition from a liquid vehicle composition and be removed so as to allow mixing of the two compositions.
  • the removable barrier may be two separate containers for the two compositions having removable openings such as caps or lids.
  • the removable barrier may be a feature of a single container having two compartments separated by the removable barrier. Removal of the barrier may damage or destroy the barrier so that it may not be used again.
  • the removable barrier may be reusable.
  • Some advantages of these ophthalmic pharmaceutical products may include: longer product shelf life, reduced degradation of the therapeutically active agent, lower levels of degradants in product, and/or improved safety and/or tolerability of the product.
  • a stabilizing composition comprises a therapeutically active agent and other components that may increase stability or are compatible with storage of the therapeutically active agent, such as a solubilizer or dispersing agent, an osmolality agent, a buffer, a preservative, a diluent or bulking agent, and the like.
  • a stabilizing composition may be a solid, containing the therapeutically active agent substantially alone.
  • the solid may be prepared by lyophilization, blending, milling, granulation or other pharmaceutical processing.
  • a stabilizing composition may also be a liquid, which contains the therapeutically active agent in solution or suspension in an appropriate stabilizing vehicle.
  • a stabilizing vehicle may be aqueous or non-aqueous, with appropriate stabilizers or excipients included as appropriate.
  • a liquid stabilizing composition may comprise a solubilizer or dispersing agent, a stabilizer, a buffer, a vehicle, etc.
  • any therapeutically active agent may be used in the stabilizing composition.
  • the therapeutically active agent is unstable to the extent that it cannot be stored for a sufficient time, such as for at least about 3 months, at least about 6 months, or at least about 1 year, in an ophthalmically acceptable liquid.
  • Some non-limiting examples of the therapeutically active agent may include: Phentolamine, Compound 1, Compound 2, DHA, EPA, ALA, cyclosporine, ketorolac, testosterone or a derivative thereof, or pharmaceutically acceptable salts thereof.
  • a solubilizer or a dispersing agent may be any compound or substance that can help to solubilize or disperse a therapeutically active agent or another dispersant in a liquid. If a surfactant is used, the surfactant used may vary, and may include any compound or salt that is surface active or can form micelles. A surfactant may be used for assisting in dissolving an excipient or an active agent, dispersing a solid or liquid in a composition, enhancing wetting, modifying drop size, stabilizing an emulsion, or a number of other purposes.
  • Useful surfactants include, but are not limited to, surfactants of the following classes: alcohols; amine oxides; block polymers; carboxylated alcohol or alkylphenol ethoxylates; carboxylic acids/fatty acids; ethoxylated alcohols; ethoxylated alkylphenols; ethoxylated aryl phenols; ethoxylated fatty acids; ethoxylated; fatty esters or oils (animal & vegetable); fatty esters; fatty acid methyl ester ethoxylates; glycerol esters; glycol esters; lanolin-based derivatives; lecithin and lecithin derivatives; lignin and lignin derivatives; methyl esters; monoglycerides and derivatives; polyethylene glycols; polymeric surfactants; propoxylated and ethoxylated fatty acids, alcohols, or alkyl phenols; protein-based surfactants; sarcosine derivatives;
  • the surfactant may include polyethylene glycol (15)-hydroxystearate (CAS Number 70142-34-6, available as SOLUTOL HS 15® from BASF), polyoxyethylene-polyoxypropylene block copolymer (CAS No. 9003-11-6, available as PLURONIC® F-68 from BASF), polyoxyethylene 40 stearate (P0E40 stearate), polysorbate 80 or polyoxyethylene (80) sorbitan monooleate (CAS No. 9005-65-6), sorbitan monostearate (CAS No. 1338-41-6, available as SPANTM 60 from Croda International PLC), polyoxyethylenglyceroltriricinoleate 35 (CAS No.
  • the amount of surfactant may vary. In some embodiments, the amount of any surfactant such as those listed above may be about 0.001% to about 5%, about 0.1% to about 2%, or about 0.1% to about 1%.
  • the solubilizer or dispersing agent may comprise: polyethylene glycol (15)-hydroxystearate, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene 40 stearate, polysorbate, sorbitane, polyoxyethylenglyceroltriricinoleate 35, or a cyclodextrin.
  • solubilizing or dispersing agents may be used that are not surface active, but may be useful in solubilizing or dispersing a solid without substantial surface activity.
  • Some non-limiting examples of other solubilizing or dispersing agents that may have mimimal surface activity include cyclodextrins, polyvinyl alcohol, povidone, hydroxypropyl methyl cellulose, poloxamers, carboxymethyl cellulose, hydroxyethyl cellulose, acrylates (e.g. PEMULEN®), etc.
  • the amount of a solubilizing or dispersing agent without substantial surface activity may be about 0.001% to about 20%.
  • the osmolality agent may vary, and may include any compound or substance useful for adjusting the osmolality of an ophthalmic liquid. Examples include, but are not limited to, salts, particularly sodium chloride or potassium chloride, mannitol glycerin, etc.
  • the amount of osmolality agent may vary depending upon whether an isosmotic, hyperosmotic, or a hyposmotic liquid is desired. In some embodiments, the amount of an osmolality agent such as those listed above may be at least about 0.0001% up to about 1%, about 2%, or about 5%.
  • the buffer may vary, and may include any weak conjugate acid-base pair suitable for maintaining a desirable pH range. Examples include, but are not limited to, acetate buffers, citrate buffers, phosphate buffers, borate buffers, lactate buffers, NaOH trolamine buffers, or a combination thereof. Acids or bases may be used to adjust the pH of these formulations as needed.
  • the amount of buffer used may vary. In some embodiments, the amount of buffer used may be sufficient so that the buffer has a concentration in a range of about 1 nM to about 100 mM in the ophthalmically acceptable liquid.
  • the preservative may vary, and may include any compound or substance suitable for prevent microbial contamination in an ophthalmic liquid subject to multiple uses from the same container.
  • Preservatives that may be used in the pharmaceutical compositions disclosed herein include, but are not limited to, cationic preservatives such as quaternary ammonium compounds including benzalkonium chloride, polyquad, and the like; guanidine-based preservatives including PHMB, chlorhexidine, and the like; chlorobutanol; mercury preservatives such as thimerosal, phenylmercuric acetate and phenylmercuric nitrate; and oxidizing preservatives such as stabilized oxychloro complexes (e.g.
  • PURITE® for liquid stabilizing compositions.
  • Combinations of preservatives are also included such as of benzalkonium ion and an oxy-chlorite moiety wherein the benzalkonium ion is benzalkonium chloride and the oxy-chlorite moiety is Purite®.
  • Other preservatives include polyhexamethylene biguanide alone and in combination with benzalkonium chloride and Purite®.
  • the diluent or bulking agent may vary, and may include any compound or substance to add bulk to a stabilizing composition for ease of handling, or for adjusting a solid stabilizing composition so that it has a desirable solid properties for handling.
  • Non-limiting examples may include mannitol, lactose, trehalose, and the like.
  • a vehicle may be used.
  • the vehicle may be any compound or substance that can dissolve or disperse any solids in a stabilizing composition so that the stabilizing composition is in a liquid form or comprises a solid dispersed in a liquid.
  • Some non-limiting examples of vehicles may include silicones, oils, or water.
  • Suitable oils include, but are not limited to anise oil, castor oil, clove oil, cassia oil, cinnamon oil, almond oil, corn oil, arachis oil, cottonseed oil, safflower oil, maize oil, linseed oil, rapeseed oil, soybean oil, olive oil, caraway oil, rosemary oil, peanut oil, peppermint oil, sunflower oil, eucalyptus oil, sesame oil, and the like.
  • a stabilizer may include any compound that is useful in stabilizing a composition, such as an antioxidant or a chelating/complexing agent.
  • the antioxidant may vary, and may include any compound or substance that is useful in reducing oxidation of any compound present in an ophthalmically acceptable liquid. Examples, but are not limited to, ascorbic acid, sodium metabisulfite, sodium thiosulfate, acetylcysteine, butylated hydroxyanisole, and butylated hydroxytoluene.
  • the chelating/complexing agent may vary, and may include any compound or substance that is capable of chelating or complexing a metal or another chemical species. Examples may include, but are not limited to, edetate disodium (EDTA), citrate, phosphate, malonate, maleate, acetate, edetate, ethanol diglycinate, diethanolglycinate, polystyrene sulfonate, etc.
  • EDTA edetate disodium
  • citrate citrate
  • phosphate malonate
  • maleate acetate
  • edetate ethanol diglycinate
  • diethanolglycinate diethanolglycinate
  • polystyrene sulfonate etc.
  • a stabilizing composition comprises polyethylene glycol (15)-hydroxystearate, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene 40 stearate, polysorbate 80, sorbitan monostearate, polyoxyethylenglyceroltriricinoleate 35, a cyclodextrin, or a combination thereof.
  • a stabilizing composition comprises potassium chloride, mannitol, sodium chloride, or a combination thereof.
  • a stabilizing composition comprises a phosphate buffer, a phosphate citrate buffer, NaOH trolamine, a lactate buffer, a borate buffer, a borate citrate buffer, or a combination thereof.
  • a stabilizing composition comprises BAK, Purite, other preservatives or preservative combinations such as combinations of preservatives including benzalkonium ion and an oxy-chlorite moiety wherein the benzalkonium ion is benzalkonium chloride and the oxy-chlorite moiety is Purite®.
  • Other preservatives include polyhexamethylene biguanide alone and in combination with benzalkonium chloride and Purite®.
  • the stabilized composition is non-preserved.
  • a stabilizing composition comprises mannitol, lactose, trehalose, or a combination thereof.
  • a stabilizing composition comprises sodium metabisulfite, ascorbic acid, EDTA, a complexing agent, or a combination thereof.
  • a stabilizing composition is an aqueous liquid that may have a pH of about 1 to about 13.
  • a stabilizing composition is a solid comprising phentolamine or a salt thereof in an amount of about 0.001% wt/wt to about 10% wt/wt and polyethylene glycol (15)-hydroxystearate in amount of about 0.001% wt/wt to about 5% wt/wt.
  • a stabilizing composition is a solid comprising phentolamine or a salt thereof in an amount of about 0.001% wt/wt to about 10% wt/wt and polyoxyethylene-polyoxypropylene block copolymer in amount of about 0.001% wt/wt to about 5% wt/wt.
  • a stabilizing composition is a solid comprising phentolamine or a salt thereof in an amount of about 0.001% wt/wt to about 10% wt/wt and polyoxyethylene 40 stearate in amount of about 0.001% wt/wt to about 1% wt/wt.
  • a stabilizing composition is a solid comprising phentolamine or a salt thereof in an amount of about 0.001% wt/wt to about 10% wt/wt and polyoxyethylenglyceroltriricinoleate 35 in amount of about 0.001% wt/wt to about 1% wt/wt.
  • a stabilizing composition is a solid comprising phentolamine or a salt thereof in an amount of about 0.001% wt/wt to about 10% wt/wt and a cyclodextrin in amount of about 0.001% wt/wt to about 20% wt/wt.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2 and a solubilizer/dispersing agent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2 and an osmolality agent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2 and a buffer listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2 and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2 and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, and a osmolality agent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, and a buffer listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, an osmolality agent listed in Table 2, and a buffer listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, an osmolality agent listed in Table 2, and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, an osmolality agent listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a buffer listed in Table 2, and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a buffer listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a preservative listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, a osmolality agent listed in Table 2, and a buffer listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, a osmolality agent listed in Table 2, and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, a osmolality agent listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, a buffer listed in Table 2, and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, a buffer listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a solubilizer/dispersing agent listed in Table 2, a preservative listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, an osmolality agent listed in Table 2, a buffer listed in Table 2, and a preservative listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, an osmolality agent listed in Table 2, a buffer listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, an osmolality agent listed in Table 2, a preservative listed in Table 2, and a diluent listed in Table 2.
  • a stabilizing composition includes a therapeutically active agent listed in Table 2, a buffer listed in Table 2, a preservative listed in Table 2, and a diluent listed in Table 2.
  • liquid stabilizing compositions are listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3 and a solubilizer/dispersing agent listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3 and a stabilizer listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3 and a buffer listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3, a solubilizer/dispersing agent listed in Table 3 and a stabilizer listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3, a solubilizer/dispersing agent listed in Table 3, and a buffer listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3, a stabilizer listed in Table 3, and a buffer listed in Table 3.
  • the stabilizing composition includes a therapeutically active agent listed in Table 3, a solubilizer/dispersing agent listed in Table 3, a stabilizer listed in Table 3, and a buffer listed in Table 3.
  • a liquid vehicle composition may be any liquid comprising a silicone or water that may be mixed with a stabilizing composition to provide a sterile ophthalmically acceptable liquid.
  • An ophthalmically acceptable liquid includes a liquid that is tolerable to a patient for topical ophthalmic use.
  • a liquid vehicle composition may also comprise any of a solubilizer or dispersing agent, a stabilizer, a buffer, and/or a preservative, as described above.
  • a liquid vehicle composition may have a pH in the range of about 5 to about 8.
  • a stabilizing composition may be about 0.001% to about 10%, or about 0.01% to about 10% of the ophthalmically acceptable liquid.
  • a liquid vehicle composition comprises polyethylene glycol (15)-hydroxystearate, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene 40 stearate, polysorbate 80, sorbitan monostearate, polyoxyethylenglyceroltriricinoleate 35, a cyclodextrin, or a combination thereof.
  • a liquid vehicle composition comprises sodium metabisulfite, ascorbic acid, EDTA, a complexing agent, or a combination thereof.
  • a liquid vehicle composition comprises a phosphate buffer, a phosphate citrate buffer, a NaOH/trolamine buffer, a lactate buffer, a borate buffer, a borate citrate buffer, or a combination thereof.
  • a liquid vehicle composition is non-preserved, or comprises benzalkonium chloride or a stabilized oxychloro complex.
  • a liquid vehicle composition is an aqueous liquid with a pH of about 5 to about 8.
  • a liquid vehicle composition comprises a silicone.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4.
  • a liquid vehicle composition comprises a stabilizer listed in Table 4.
  • a liquid vehicle composition comprises a buffer listed in Table 4.
  • a liquid vehicle composition comprises a preservative listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4 and a stabilizer listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4 and a buffer listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4 and a preservative listed in Table 4.
  • a liquid vehicle composition comprises a stabilizer listed in Table 4 and a buffer listed in Table 4.
  • a liquid vehicle composition comprises a stabilizer listed in Table 4 and a preservative listed in Table 4.
  • a liquid vehicle composition comprises a buffer listed in Table 4 and a preservative listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4, a stabilizer listed in Table 4, and a buffer listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4, a stabilizer listed in Table 4, and a preservative listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4, a buffer listed in Table 4, and a preservative listed in Table 4.
  • a liquid vehicle composition comprises a stabilizer listed in Table 4, a buffer listed in Table 4, and a preservative listed in Table 4.
  • a liquid vehicle composition comprises a solubilizer/dispersing agent listed in Table 4, a stabilizer listed in Table 4, a buffer listed in Table 4, and a preservative listed in Table 4.

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  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Ophthalmology & Optometry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Biochemistry (AREA)
  • Molecular Biology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US13/557,611 2011-07-26 2012-07-25 Two part formulation system for opthalmic delivery Abandoned US20130029919A1 (en)

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US13/557,611 US20130029919A1 (en) 2011-07-26 2012-07-25 Two part formulation system for opthalmic delivery
US15/135,925 US9616017B2 (en) 2011-07-26 2016-04-22 Two part formulation system for ophthalmic delivery
US15/483,162 US10314887B2 (en) 2011-07-26 2017-04-10 Two part formulation system for ophthalmic delivery
US16/436,200 US20190290722A1 (en) 2011-07-26 2019-06-10 Two part formulation system for ophthalmic delivery

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US201161511753P 2011-07-26 2011-07-26
US13/557,611 US20130029919A1 (en) 2011-07-26 2012-07-25 Two part formulation system for opthalmic delivery

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US15/135,925 Expired - Fee Related US9616017B2 (en) 2011-07-26 2016-04-22 Two part formulation system for ophthalmic delivery
US15/483,162 Active US10314887B2 (en) 2011-07-26 2017-04-10 Two part formulation system for ophthalmic delivery
US16/436,200 Abandoned US20190290722A1 (en) 2011-07-26 2019-06-10 Two part formulation system for ophthalmic delivery

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US15/483,162 Active US10314887B2 (en) 2011-07-26 2017-04-10 Two part formulation system for ophthalmic delivery
US16/436,200 Abandoned US20190290722A1 (en) 2011-07-26 2019-06-10 Two part formulation system for ophthalmic delivery

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US (4) US20130029919A1 (enExample)
EP (2) EP3329896A1 (enExample)
JP (2) JP6271423B2 (enExample)
KR (1) KR102031997B1 (enExample)
CN (2) CN103732202A (enExample)
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014121027A1 (en) * 2013-02-01 2014-08-07 Oculars Pharma, Llc Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US9089560B2 (en) 2013-02-01 2015-07-28 Ocularis Pharma, Llc Methods and compositions for daily ophthalmic administration of phentolamine to improve visual performance
US20170112936A1 (en) * 2014-05-23 2017-04-27 Imprimis Pharmaceuticals, Inc. Pharmaceutical compositions comprising gels and methods for fabricating thereof
CN108707212A (zh) * 2018-05-02 2018-10-26 上海交通大学 一种水溶性共轭聚合物纳米粒子的可控制备方法
CN110234324A (zh) * 2016-12-16 2019-09-13 国际药品株式会社 含有柳氮磺胺吡啶和透明质酸的眼用组合物
US10993932B2 (en) 2018-10-26 2021-05-04 Ocuphire Pharma, Inc. Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders
US11566005B2 (en) 2021-05-18 2023-01-31 Ocuphire Pharma, Inc. Highly pure phentolamine mesylate and methods for making same
US12161629B2 (en) 2018-10-15 2024-12-10 Opus Genetics, Inc. Methods and compositions for treatment of glaucoma and related conditions

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101587412B1 (ko) 2014-10-17 2016-01-21 주식회사 휴온스 사이클로스포린 및 트레할로스를 포함하는 안과용 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5409904A (en) * 1984-11-13 1995-04-25 Alcon Laboratories, Inc. Hyaluronic acid compositions and methods
US5474979A (en) * 1994-05-17 1995-12-12 Allergan, Inc. Nonirritating emulsions for sensitive tissue
US7458741B2 (en) * 2003-05-08 2008-12-02 R.P. Scherer Technologies, Inc. Multiple compartment storage and dispensing apparatus
WO2009046967A1 (en) * 2007-10-08 2009-04-16 Fovea Pharmaceuticals Sa Aqueous ophthalmic formulations

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6452722A (en) * 1987-05-01 1989-02-28 Anjierini Pharmaceut Inc Ophthalmic composition
US4879304A (en) 1987-05-01 1989-11-07 Angelini Pharmaceuticals Ltd. Ophthalmic compositions and process for preparing
JPH0558906A (ja) * 1991-09-06 1993-03-09 Sankyo Co Ltd シクロスポリン点眼製剤
CN1185953A (zh) * 1996-12-27 1998-07-01 刘伟中 富氧舒眼液及其生产工艺
AR002194A1 (es) * 1997-03-17 1998-01-07 Sanchez Reynaldo Alemany Instrumento computarizado para el analisis del movimiento.
PT1073413E (pt) * 1998-04-29 2005-04-29 Novartis Ag Metodos e composicoes para estabilizacao de composicoes de acetilcolina
FR2787325B1 (fr) 1998-12-17 2001-01-26 Oreal Nanoemulsion a base d'esters gras de sorbitan oxyethylenes ou non oxyethylenes, et ses utilisations dans les domaines cosmetique, dermatologique et/ou ophtalmologique
US6291498B1 (en) * 1999-09-16 2001-09-18 Gerald Horn Method for optimizing pupil size using alpha antagonist
WO2001041757A1 (en) * 1999-12-10 2001-06-14 Senju Pharmaceutical Co., Ltd. Cyclodextrin-containing pharmaceutical composition
US20060257388A1 (en) * 2005-05-13 2006-11-16 Julius Knowles Drug delivery systems for stabilized formulations of alpha adrenergic receptor antagonists and the uses thereof
US20080004310A1 (en) * 2006-06-19 2008-01-03 Applied Pharmacy Services, Inc. Lyophilized pharmaceutical composition
US9561178B2 (en) * 2006-07-25 2017-02-07 Allergan, Inc. Cyclosporin compositions
US20080095754A1 (en) 2006-10-18 2008-04-24 Burke Susan E Ophthalmic compositions comprising diglycine
CN101528217A (zh) * 2006-10-18 2009-09-09 博士伦公司 包含二甘氨酸的眼用组合物
DE102007021862A1 (de) 2007-05-10 2008-11-13 Merck Patent Gmbh Wässrige pharmazeutische Zubereitung
WO2009020145A1 (ja) * 2007-08-09 2009-02-12 Senju Pharmaceutical Co., Ltd. ピレノキシン含有二液性点眼剤
GB0718816D0 (en) * 2007-09-26 2007-11-07 Intray Ltd Time indicator device
JP5668476B2 (ja) 2007-10-08 2015-02-12 オーリニア・ファーマシューティカルズ・インコーポレイテッドＡｕｒｉｎｉａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． カルシニューリン阻害剤またはｍＴＯＲ阻害剤を含む眼科用組成物
WO2009088570A1 (en) * 2008-01-04 2009-07-16 Sirion Therapeutics, Inc. Stable aqueous cyclosporin compositions
US20090221984A1 (en) * 2008-03-03 2009-09-03 Akram Girgis Method and apparatus for providing therapeutically effective dosage formulations of lidocaine with and without epinephrine
PL2285364T3 (pl) * 2008-05-07 2015-04-30 Univ California Terapeutyczne uzupełnienie i wzbogacenie smarowania powierzchni oka
CN102028697B (zh) * 2009-09-27 2014-01-08 上海信谊药厂有限公司 含非离子表面活性剂的拉坦前列素滴眼液及制备方法
US20110178147A1 (en) * 2009-10-20 2011-07-21 Allergan, Inc. Compositions and methods for controlling pupil dilation
US8952051B2 (en) * 2009-11-05 2015-02-10 Allergan, Inc. Ophthalmic formulations containing substituted gamma lactams and methods for use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5409904A (en) * 1984-11-13 1995-04-25 Alcon Laboratories, Inc. Hyaluronic acid compositions and methods
US5474979A (en) * 1994-05-17 1995-12-12 Allergan, Inc. Nonirritating emulsions for sensitive tissue
US7458741B2 (en) * 2003-05-08 2008-12-02 R.P. Scherer Technologies, Inc. Multiple compartment storage and dispensing apparatus
WO2009046967A1 (en) * 2007-10-08 2009-04-16 Fovea Pharmaceuticals Sa Aqueous ophthalmic formulations

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Lallemand et al., "Cyclosporine A delivery to the eye: A pharmaceutical challenge," Eur. J. Pharma. Biopharma. 56:307-308 92003). *
Wegner et al., "Synthesis of Cyclosporine. Total synthesis of Cylsporin A and Cyclosporin H, two fungal metabolites isolated from the species Tolypocladium Inflatum Gams," Helv. Chim. Acta 67:502-525 (1984). *

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US11000509B2 (en) 2013-02-01 2021-05-11 Ocuphire Pharma, Inc. Methods and compositions for daily ophthalmic administration of phentolamine to improve visual performance
WO2014121027A1 (en) * 2013-02-01 2014-08-07 Oculars Pharma, Llc Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US12350366B2 (en) 2013-02-01 2025-07-08 Opus Genetics, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US9789088B2 (en) 2013-02-01 2017-10-17 Ocularis Pharma, Llc Methods and compositions for daily ophthalmic administration of phentolamine to improve visual performance
US9795560B2 (en) 2013-02-01 2017-10-24 Ocularis Pharma, Llc Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US11844858B2 (en) 2013-02-01 2023-12-19 Ocuphire Pharma, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US10772829B2 (en) 2013-02-01 2020-09-15 Ocuphire Pharma, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
AU2018200566B2 (en) * 2013-02-01 2019-06-13 Ocuphire Pharma, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
AU2018200566B9 (en) * 2013-02-01 2019-06-20 Ocuphire Pharma, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US11090261B2 (en) 2013-02-01 2021-08-17 Ocuphire Pharma, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US9089560B2 (en) 2013-02-01 2015-07-28 Ocularis Pharma, Llc Methods and compositions for daily ophthalmic administration of phentolamine to improve visual performance
US10278918B2 (en) 2013-02-01 2019-05-07 Ocuphire Pharma, Inc. Aqueous ophthalmic solutions of phentolamine and medical uses thereof
US11717510B2 (en) 2013-02-01 2023-08-08 Ocuphire Pharma, Inc. Methods and compositions for daily ophthalmic administration of phentolamine to improve visual performance
US20170112936A1 (en) * 2014-05-23 2017-04-27 Imprimis Pharmaceuticals, Inc. Pharmaceutical compositions comprising gels and methods for fabricating thereof
CN110234324A (zh) * 2016-12-16 2019-09-13 国际药品株式会社 含有柳氮磺胺吡啶和透明质酸的眼用组合物
CN108707212A (zh) * 2018-05-02 2018-10-26 上海交通大学 一种水溶性共轭聚合物纳米粒子的可控制备方法
US12161629B2 (en) 2018-10-15 2024-12-10 Opus Genetics, Inc. Methods and compositions for treatment of glaucoma and related conditions
US11400077B2 (en) 2018-10-26 2022-08-02 Ocuphire Pharma, Inc. Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders
US10993932B2 (en) 2018-10-26 2021-05-04 Ocuphire Pharma, Inc. Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders
US12016841B2 (en) 2018-10-26 2024-06-25 Ocuphire Pharma, Inc. Methods and compositions for treatment of presbyopia, mydriasis, and other ocular disorders
US12201616B2 (en) 2018-10-26 2025-01-21 Opus Genetics, Inc. Methods and compositions for treatment of mydriasis
US12201615B2 (en) 2018-10-26 2025-01-21 Opus Genetics, Inc. Methods and compositions for treatment of mydriasis
US11566005B2 (en) 2021-05-18 2023-01-31 Ocuphire Pharma, Inc. Highly pure phentolamine mesylate and methods for making same
US11976044B2 (en) 2021-05-18 2024-05-07 Ocuphire Pharma, Inc. Highly pure phentolamine mesylate

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US20190290722A1 (en) 2019-09-26
AU2017251720A1 (en) 2017-11-09
US20170209532A1 (en) 2017-07-27
EP3329896A1 (en) 2018-06-06
JP2018062521A (ja) 2018-04-19
JP6271423B2 (ja) 2018-01-31
US20160235666A1 (en) 2016-08-18
CA2843267A1 (en) 2013-01-31
KR20140054125A (ko) 2014-05-08
US9616017B2 (en) 2017-04-11
AU2020267145A1 (en) 2020-12-03
CN108514547A (zh) 2018-09-11
CA2843267C (en) 2020-08-18
EP2736475A1 (en) 2014-06-04
AU2019203069A1 (en) 2019-05-23
KR102031997B1 (ko) 2019-10-14
AU2012286857A1 (en) 2014-02-20
CN103732202A (zh) 2014-04-16

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