US20110139995A1 - Methods and devices to test diffusion rates of ocular drug delivery systems - Google Patents
Methods and devices to test diffusion rates of ocular drug delivery systems Download PDFInfo
- Publication number
- US20110139995A1 US20110139995A1 US13/034,522 US201113034522A US2011139995A1 US 20110139995 A1 US20110139995 A1 US 20110139995A1 US 201113034522 A US201113034522 A US 201113034522A US 2011139995 A1 US2011139995 A1 US 2011139995A1
- Authority
- US
- United States
- Prior art keywords
- canceled
- ophthalmic lens
- solution
- ketotifen
- pharmaceutical agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/16—Intraocular lenses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
- A61F2240/008—Means for testing implantable prostheses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
Definitions
- This invention related to devices and methods to test the diffusion rates of pharmaceutical agents through ophthalmic lens.
- FIG. 1 Illustrates a container with a sample area and a detecting area
- FIG. 2 Illustrates a decoupled testing apparatus
- FIG. 3 Illustrates a closed testing apparatus.
- This invention includes a method of measuring the discharge rate of a pharmaceutical agent from an ophthalmic lens, wherein the method comprises the steps of
- pharmaceutical agents refers to pharmaceutical or nutraceutical compounds used to treat conditions of the eye, and such compound degrade in the presence of oxygen and certain transition metals.
- pharmaceutical compounds include antihistamines, antibiotics, antibacterial agents, antiviral agents, antifungal agents, analgesics, anesthetics, antiallergenic agents, mast cell stabilizers, steroidal and non-steroidal anti-inflammatory agents, angiogenesis inhibitors; antimetabolites, fibrinolytics, neuroprotective drugs, angiostatic steroids, mydriatics, cyclopegic mydriatics; miotics; vasoconstrictors; vasodilators, anticlotting agents; anticancer agents, antisense agents, immunomodulatory agents, carbonic anhydrase inhibitors, integrin antabonistsl; cyclooxygenase inhibitors, VEGF antagonists; immunosuppressant agents and the like.
- examples of pharmaceutical compounds include but are not limited to acrivastine, antazoline, astemizole, azatadine, azelastine, buclizine, bupivacaine, cetirizine, clemastine, cyclizine, cyproheptadine, ebastine, emedastine, ephedrine, eucatropine, fexofenadine, homatropine, hydroxyzine, ketotifen, levocabastine, levoceterizine, lomefloxacin, meclizine, mepivacaine, mequitazine, methdilazine, methapyrilene, mianserin, naphazoline norastemizole, norebastine, ofloxacin, oxymetazoline, pheniramine, phenylephrine, physostigmine, picumast, promethazine, scopolamine, terf
- Preferred pharmaceutical compounds include acrivatine, antazoline, astemizole, azatadine, azelastine, clemastine, cyproheptadine, ebastine, emedastine, eucatropine, fexofenadine, homatropine, hydroxyzine, ketotife, levocabastine, levoceterizine, meclizine, mequitazine, methdialazine, methapyrilene, norastemizole, norebastine, oxymetazoline, physootigmine, picumast, promethazine, scopolamine, terfenadine, tetrahyerozoline, fimilol, trimeprazine, triprolidine, and pharmaceutically acceptable salts thereof.
- Particularly preferred pharmaceutical compounds include phenarimine, ketotifen, ketotifen fumarate nor ketotifen fumarate, 11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde (CAS# 147084-10-4), olapatadine and mixtures thereof. More particularly preferred pharmaceutical compounds include ketotifen fumarate, 11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde (CAS# 147084-10-4) and mixtures thereof.
- nutraceutical compounds include vitamins and supplements such as vitamins A, D, E, lutein, zeaxanthin, lipoic acid, flavonoids, ophthalmicially compatible fatty acids, such as omega 3 and omega 6 fatty acids, combinations thereof, combinations with pharmaceutical compounds and the like.
- the methods of the invention may be used to detect the discharge rate (or uptake rate) of ophthalmic lenses containing about 8 ⁇ g or more of pharmaceutical agent.
- the discharge rate for ophthalmic lenses that contain about 8 ⁇ g to about 90 ⁇ g, more preferably about 10 ⁇ g to about 40 ⁇ g, more preferably about 10 ⁇ g to about 25 ⁇ g may be determined by the methods of this invention.
- Ophthalmic lens refers to a device that resides in or on the eye. These devices can provide optical correction or may be cosmetic. Ophthalmic lenses include but are not limited to soft contact lenses, intraocular lenses, overlay lenses, ocular inserts, and optical inserts.
- the preferred lenses of the invention are soft contact lenses made from silicone elastomers or hydrogels, which include but are not limited to silicone hydrogels, and fluorohydrogels.
- Soft contact lens formulations are disclosed in U.S. Pat. No. 5,710,302, WO 9421698, EP 406161, JP 2000016905, U.S. Pat. No. 5,998,498, U.S. Pat. No. 6,087,415, U.S. Pat. No.
- the particularly preferred ophthalmic lenses of the inventions are known by the United States Approved Names of acofilcon A, alofilcon A, alphafilcon A, amifilcon A, astifilcon A, atalafilcon A, balafilcon A, bisfilcon A, bufilcon A, comfilcon, crofilcon A, cyclofilcon A,balilcon A, deltafilcon A, deltafilcon B, dimefilcon A, drooxifilcon A, epsifilcon A, esterifilcon A, etafilcon A, focofilcon A, galfilcon A, genfilcon A, govafilcon A, hefilcon A, hefilcon B, hefilcon D, hilafilcon A, hilafilcon B, hioxifilcon B, hioxifilcon C, hixoifilcon A, hydrofilcon A, lenefilcon A, licryfilcon A, licryfilcon B, lidofilcon
- More particularly preferred ophthalmic lenses of the invention are galfilcon A, genfilcon A, lenefilcon A, senofilcon A, comfilcon, lotrafilcon A, lotraifilcon B, and balafilcon A.
- the most preferred lenses include etafilcon A, nelfilcon A, hilafilcon, vifilcon, and polymacon.
- Detecting chamber refers to an enclosure that houses the solution but not the ophthalmic lens. It is attached to the sampling chamber to permit solution to flow from one chamber to the other.
- the detecting chamber may be closed, open, or connected to other devices such as an HPLC.
- the detecting chamber preferably contains an optically transparent portion. This optically transparent portion permits light to pass through to the ophthalmic lens and the solution as well as reflect light from those sources. It is preferred that the detecting chamber contain an optically transparent portion.
- sample chamber refers to an enclosure that is attached to the detecting chamber to permit the flow of solution from one chamber to the other.
- the sample chamber may be closed open, or connected to a device that delivers solutions, other ophthalmic lenses, inert gases and the like to the chamber.
- solutions may be water-based solutions.
- Typical solutions include, without limitation, saline solutions, other buffered solutions, and deionized water.
- the preferred aqueous solution is deioinized water or saline solution containing salts including, without limitation, sodium chloride, sodium borate, sodium phosphate, sodium hydrogenphosphate, sodium dihydrogenphosphate, or the corresponding potassium salts of the same.
- salts including, without limitation, sodium chloride, sodium borate, sodium phosphate, sodium hydrogenphosphate, sodium dihydrogenphosphate, or the corresponding potassium salts of the same.
- the buffered solutions may additionally include 2-(N-morpholino)ethanesulfonic acid (MES), sodium hydroxide, 2,2-bis(hydroxymethyl)-2,2′,2′′-nitrilotriethanol, n-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, citric acid, sodium citrate, sodium carbonate, sodium bicarbonate, acetic acid, sodium acetate, ethylenediamine tetraacetic acid and the like and combinations thereof.
- the solution is a borate buffered or phosphate buffered saline solution or deionized water.
- the particularly preferred solution contains about 1,850 ppm to about 18,500 ppm sodium borate, most particularly preferred about 3,700 ppm of sodium borate.
- the “effective amount” of the solution is enough to immerse the lens, but not so much that the level of pharmaceutical agent that is discharged from the lens (or as described below absorbed by the lens) cannot be detected.
- the preferred effective amount is about 1 mL to about 3 mL, more preferably about 1 mL to about 2 mL.
- the “second amount” of solution is substantially similar to the effective amount but is not necessarily equivalent to the effective amount. It is preferred that the second amount is about 0.5 mL to about 3 mL, more preferably about 0.5 mL to about 1 mL.
- monitoring refers to methods of analyzing the solution to determine the concentration of pharmaceutical agent in the solution. Examples of such detecting methods include but are not limited to HPLC, UV Spectormeters and the like. The preferred monitoring method is UV visible spectroscopy.
- the invention includes, a method of measuring the uptake rate of a pharmaceutical agent to an ophthalmic lens, wherein the method comprises the steps of
- FIG. 1 illustrates a chamber that is used in the methods of the invention.
- An ophthalmic lens 10 and a solution are inserted into container 20 from end 30 .
- the solution fills the detecting chamber 40 and the sample chamber 60 .
- Detecting chamber 40 is bordered on its sides by solid areas 50 .
- Lens 10 rests in the sample chamber 60 , which starts at end 30 and terminates in at the detecting area.
- Container 20 is made of an optically transparent material area.
- a UV-Vis spectrometer is placed above the detecting chamber and the spectrometer monitors the amount of increase or decrease at wavelengths associated with the pharmaceutical agent.
- the invention includes, a method of measuring the discharge rate of a pharmaceutical agent from an ophthalmic lens, wherein the method comprises the steps of
- the terms pharmaceutical agent, ophthalmic lens, solution(s) and monitoring all have their aforementioned meanings and preferred ranges.
- the term “sufficient amount” refers to the quantity of solution that permits one to monitor the pharmaceutical agent as it disperses from the ophthalmic lens. For example, if an ophthalmic lens contains about 100 mg of ketotifen fumarate, and the solution is deionized water, the sufficient amount of deionized water is about 25 mL.
- testing apparatus refers to a container that encloses the ophthalmic lens and permits solution to flow through said lens.
- FIGS. 2 and 3 illustrate a suitable testing apparatus.
- Male top 100 contains a convex portion 110 , an O-ring 112 and holder 114 .
- the convex portion 110 has several radial openings 116 , to permit solution to reach an ophthalmic lens enclosed in the testing apparatus.
- the female bottom 200 has a concave portion 210 and a seating ridge 212 that is sized to mate with the male top when the testing apparatus is closed.
- the concave portion 210 contains several apertures to permit solution to reach enclosed ophthalmic lenses.
- FIG. 3 illustrates that holder 114 is adapted to connect to a shaft 118 .
- This shaft is connected to a motor that rotates the testing apparatus in solutions.
- the testing apparatuses are rotated during diffusion testing.
- the system is maintained at room temperature throughout the solution making process. All components 1-6 are added in any order and stirred using a magnetic or mechanical stirrer until the solution is homogeneous. Ketotifen fumarate is added last and the mixture is stirred for an additional 30 minutes or as long as it takes to make the solution homogeneous.
- 1-Day Acuvue® Brand Contact Lenses (etafilcon A +3.00) were removed from their packages and repackaged in glass vials containing 3.0 mL of the 25 ⁇ g/mL ketotifen fumarate solutions described above to produce K-Lens 25.
- the vials were sealed with PTFE coated rubber stoppers and heated for 18 minutes at 124° C.
- a lens of Example 1 was placed in a chamber of FIG. 1 with 1 mL of packaging solution (ingredients 1-5 of Example 1 in the same proportions) that does not contain ketotifen. UV-VIS spectrometer readings were taken at 299 nm at one minute intervals and plotted to determine the dissolution rate of ketotifen from the lens.
- a 1-Day Acuvue® Brand Contact Lens was placed in a chamber of FIG. 1 with 1 mL of the 25 ⁇ g/mL ketotifen fumarate of Example 1. UV-VIS spectrometer readings were taken at 299 nm at one minute intervals and plotted to determine the uptake rate of ketotifen to the lens.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Food Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Eyeglasses (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Methods of detecting the discharge and uptake rates of ophthalmic lenses containing pharmaceutical agents are disclosed herein.
Description
- This application is a non-provisional filing of a provisional application, U.S. Ser. No. 60/863,587, filed on Oct. 31, 2006.
- This invention related to devices and methods to test the diffusion rates of pharmaceutical agents through ophthalmic lens.
- Most diseases of the eye are treated with topical ophthalmic solutions containing pharmaceutical agents. It has been postulated that delivery and efficacy of these agents would be greatly increased if the agents were incorporated in ophthalmic lenses and those lenses were used as drug delivery devices. These agents may be added to the ophthalmic lenses by a variety of methods including soaking the agent into a formed lens, adding the agent to the formulation of the lens prior to its formation and the like. Despite the teachings of many, to date, there are no commercially available products for patients.
- In order to gain approval for such a device, one must demonstrate the rate at which the pharmaceutical agent diffuses into and out of the ophthalmic lens. One of the possible reasons for the lack of commercial products is that current test methods to demonstrate dissolution rates of pharmaceutical agents through contact lenses are cumbersome. These methods rely on discrete sampling and are known to be labor intensive and expensive. In addition, these methods do not allow one to obtain continuous dissolution data. Therefore, it would be useful if devices and methods that to determine dissolution rates, and more particularly, continuous dissolution rates of pharmaceutical agents through ophthalmic lenses, would be useful. This need is met by the following invention
-
FIG. 1 Illustrates a container with a sample area and a detecting area -
FIG. 2 . Illustrates a decoupled testing apparatus -
FIG. 3 . Illustrates a closed testing apparatus. - This invention includes a method of measuring the discharge rate of a pharmaceutical agent from an ophthalmic lens, wherein the method comprises the steps of
- (a) placing said ophthalmic lens comprising said pharmaceutical agent in a container comprising a sample chamber and a detecting chamber, wherein said sample chamber is sized to contain an ophthalmic lens and an effective amount of a solution and said detecting chamber is sized contain a second amount the solution, but is not sized to contain an ophthalmic lens, wherein said sample chamber and said detecting chamber are connected to allow solution to flow between said sample chamber to said detecting chamber but to contain said ophthalmic lens within said sample chamber,
- (b) monitoring the detecting chamber to determine the presence or absence of said pharmaceutical agent in solution contained within said detecting chamber.
- As used herein, “pharmaceutical agents refers to pharmaceutical or nutraceutical compounds used to treat conditions of the eye, and such compound degrade in the presence of oxygen and certain transition metals. Examples of pharmaceutical compounds include antihistamines, antibiotics, antibacterial agents, antiviral agents, antifungal agents, analgesics, anesthetics, antiallergenic agents, mast cell stabilizers, steroidal and non-steroidal anti-inflammatory agents, angiogenesis inhibitors; antimetabolites, fibrinolytics, neuroprotective drugs, angiostatic steroids, mydriatics, cyclopegic mydriatics; miotics; vasoconstrictors; vasodilators, anticlotting agents; anticancer agents, antisense agents, immunomodulatory agents, carbonic anhydrase inhibitors, integrin antabonistsl; cyclooxygenase inhibitors, VEGF antagonists; immunosuppressant agents and the like. Particularly, examples of pharmaceutical compounds include but are not limited to acrivastine, antazoline, astemizole, azatadine, azelastine, buclizine, bupivacaine, cetirizine, clemastine, cyclizine, cyproheptadine, ebastine, emedastine, ephedrine, eucatropine, fexofenadine, homatropine, hydroxyzine, ketotifen, levocabastine, levoceterizine, lomefloxacin, meclizine, mepivacaine, mequitazine, methdilazine, methapyrilene, mianserin, naphazoline norastemizole, norebastine, ofloxacin, oxymetazoline, pheniramine, phenylephrine, physostigmine, picumast, promethazine, scopolamine, terfenadine, tetrahydrozoline, thiethylperazine, timolol, trimeprazine, triprolidine, pharmaceutically acceptable salts and mixtures thereof. Preferred pharmaceutical compounds include acrivatine, antazoline, astemizole, azatadine, azelastine, clemastine, cyproheptadine, ebastine, emedastine, eucatropine, fexofenadine, homatropine, hydroxyzine, ketotife, levocabastine, levoceterizine, meclizine, mequitazine, methdialazine, methapyrilene, norastemizole, norebastine, oxymetazoline, physootigmine, picumast, promethazine, scopolamine, terfenadine, tetrahyerozoline, fimilol, trimeprazine, triprolidine, and pharmaceutically acceptable salts thereof. Particularly preferred pharmaceutical compounds include phenarimine, ketotifen, ketotifen fumarate nor ketotifen fumarate, 11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde (CAS# 147084-10-4), olapatadine and mixtures thereof. More particularly preferred pharmaceutical compounds include ketotifen fumarate, 11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde (CAS# 147084-10-4) and mixtures thereof.
- Examples of nutraceutical compounds include vitamins and supplements such as vitamins A, D, E, lutein, zeaxanthin, lipoic acid, flavonoids, ophthalmicially compatible fatty acids, such as omega 3 and omega 6 fatty acids, combinations thereof, combinations with pharmaceutical compounds and the like. The methods of the invention may be used to detect the discharge rate (or uptake rate) of ophthalmic lenses containing about 8 μg or more of pharmaceutical agent. Preferably, the discharge rate for ophthalmic lenses that contain about 8 μg to about 90 μg, more preferably about 10 μg to about 40 μg, more preferably about 10 μg to about 25 μg may be determined by the methods of this invention.
- As used herein, “ophthalmic lens” refers to a device that resides in or on the eye. These devices can provide optical correction or may be cosmetic. Ophthalmic lenses include but are not limited to soft contact lenses, intraocular lenses, overlay lenses, ocular inserts, and optical inserts. The preferred lenses of the invention are soft contact lenses made from silicone elastomers or hydrogels, which include but are not limited to silicone hydrogels, and fluorohydrogels. Soft contact lens formulations are disclosed in U.S. Pat. No. 5,710,302, WO 9421698, EP 406161, JP 2000016905, U.S. Pat. No. 5,998,498, U.S. Pat. No. 6,087,415, U.S. Pat. No. 5,760,100, U.S. Pat. No. 5,776,999, U.S. Pat. No. 5,789,461, U.S. Pat. No. 5,849,811, and U.S. Pat. No. 5,965,631. The foregoing references are hereby incorporated by reference in their entirety. The particularly preferred ophthalmic lenses of the inventions are known by the United States Approved Names of acofilcon A, alofilcon A, alphafilcon A, amifilcon A, astifilcon A, atalafilcon A, balafilcon A, bisfilcon A, bufilcon A, comfilcon, crofilcon A, cyclofilcon A, darfilcon A, deltafilcon A, deltafilcon B, dimefilcon A, drooxifilcon A, epsifilcon A, esterifilcon A, etafilcon A, focofilcon A, galfilcon A, genfilcon A, govafilcon A, hefilcon A, hefilcon B, hefilcon D, hilafilcon A, hilafilcon B, hioxifilcon B, hioxifilcon C, hixoifilcon A, hydrofilcon A, lenefilcon A, licryfilcon A, licryfilcon B, lidofilcon A, lidofilcon B, lotrafilcon A, lotrafilcon B, mafilcon A, mesifilcon A, methafilcon B, mipafilcon A, nelfilcon A, netrafilcon A, ocufilcon A, ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ofilcon A, omafilcon A, oxyfilcon A, pentafilcon A, perfilcon A, pevafilcon A, phemfilcon A, polymacon, senofilcon A, silafilcon A, siloxyfilcon A, tefilcon A, tetrafilcon A, trifilcon A, vifilcon, and xylofilcon A. More particularly preferred ophthalmic lenses of the invention are galfilcon A, genfilcon A, lenefilcon A, senofilcon A, comfilcon, lotrafilcon A, lotraifilcon B, and balafilcon A. The most preferred lenses include etafilcon A, nelfilcon A, hilafilcon, vifilcon, and polymacon.
- “Detecting chamber” refers to an enclosure that houses the solution but not the ophthalmic lens. It is attached to the sampling chamber to permit solution to flow from one chamber to the other. The detecting chamber may be closed, open, or connected to other devices such as an HPLC. The detecting chamber preferably contains an optically transparent portion. This optically transparent portion permits light to pass through to the ophthalmic lens and the solution as well as reflect light from those sources. It is preferred that the detecting chamber contain an optically transparent portion.
- As used herein “sample chamber” refers to an enclosure that is attached to the detecting chamber to permit the flow of solution from one chamber to the other. The sample chamber may be closed open, or connected to a device that delivers solutions, other ophthalmic lenses, inert gases and the like to the chamber.
- The “solutions” that are used in methods of this invention may be water-based solutions. Typical solutions include, without limitation, saline solutions, other buffered solutions, and deionized water. The preferred aqueous solution is deioinized water or saline solution containing salts including, without limitation, sodium chloride, sodium borate, sodium phosphate, sodium hydrogenphosphate, sodium dihydrogenphosphate, or the corresponding potassium salts of the same. These ingredients are generally combined to form buffered solutions that include an acid and its conjugate base, so that addition of acids and bases cause only a relatively small change in pH. The buffered solutions may additionally include 2-(N-morpholino)ethanesulfonic acid (MES), sodium hydroxide, 2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol, n-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, citric acid, sodium citrate, sodium carbonate, sodium bicarbonate, acetic acid, sodium acetate, ethylenediamine tetraacetic acid and the like and combinations thereof. Preferably, the solution is a borate buffered or phosphate buffered saline solution or deionized water. The particularly preferred solution contains about 1,850 ppm to about 18,500 ppm sodium borate, most particularly preferred about 3,700 ppm of sodium borate. The “effective amount” of the solution is enough to immerse the lens, but not so much that the level of pharmaceutical agent that is discharged from the lens (or as described below absorbed by the lens) cannot be detected. The preferred effective amount is about 1 mL to about 3 mL, more preferably about 1 mL to about 2 mL. The “second amount” of solution is substantially similar to the effective amount but is not necessarily equivalent to the effective amount. It is preferred that the second amount is about 0.5 mL to about 3 mL, more preferably about 0.5 mL to about 1 mL.
- As used herein “monitoring” refers to methods of analyzing the solution to determine the concentration of pharmaceutical agent in the solution. Examples of such detecting methods include but are not limited to HPLC, UV Spectormeters and the like. The preferred monitoring method is UV visible spectroscopy.
- Further the invention includes, a method of measuring the uptake rate of a pharmaceutical agent to an ophthalmic lens, wherein the method comprises the steps of
- (a) placing said ophthalmic lens in container comprising a sample chamber and a detecting chamber, wherein said sample chamber is sized to contain an ophthalmic lens and an effective amount of a solution and said detecting chamber is sized to contain a second amount the solution, but is not sized to contain an ophthalmic lens, wherein said sample chamber and said detecting chamber are connected to allow solution to flow between said sample chamber to said detecting chamber but to contain said ophthalmic lens within said sample chamber and said effective amount of solution and said second amount of solution comprise a pharmaceutical agent,
- (b) monitoring the detecting chamber to determine the presence or absence of said pharmaceutical agent in solution contained within said detecting chamber. The terms pharmaceutical agent, sample chamber, ophthalmic lens detecting, chamber, solution, effective amount, second amount and monitoring all have their aforementioned meanings and preferred ranges.
-
FIG. 1 illustrates a chamber that is used in the methods of the invention. Anophthalmic lens 10 and a solution are inserted intocontainer 20 fromend 30. The solution fills the detectingchamber 40 and thesample chamber 60. Detectingchamber 40 is bordered on its sides bysolid areas 50.Lens 10 rests in thesample chamber 60, which starts atend 30 and terminates in at the detecting area.Container 20 is made of an optically transparent material area. A UV-Vis spectrometer is placed above the detecting chamber and the spectrometer monitors the amount of increase or decrease at wavelengths associated with the pharmaceutical agent. - Still further the invention includes, a method of measuring the discharge rate of a pharmaceutical agent from an ophthalmic lens, wherein the method comprises the steps of
- (a) placing said ophthalmic lens comprising said pharmaceutical agent a testing apparatus, wherein said testing apparatus is sized to enclose said ophthalmic lens and to permit solutions to contact said ophthalmic lens,
- (b) placing said enclosed ophthalmic lens into a sufficient amount of solutions,
- (c) monitoring sufficient amount of solution to determine the presence or absence of said pharmaceutical agent in said solution.
- The terms pharmaceutical agent, ophthalmic lens, solution(s) and monitoring all have their aforementioned meanings and preferred ranges. The term “sufficient amount” refers to the quantity of solution that permits one to monitor the pharmaceutical agent as it disperses from the ophthalmic lens. For example, if an ophthalmic lens contains about 100 mg of ketotifen fumarate, and the solution is deionized water, the sufficient amount of deionized water is about 25 mL.
- The term testing apparatus refers to a container that encloses the ophthalmic lens and permits solution to flow through said lens.
FIGS. 2 and 3 , illustrate a suitable testing apparatus. - Male top 100 contains a
convex portion 110, an O-ring 112 andholder 114. Theconvex portion 110 has severalradial openings 116, to permit solution to reach an ophthalmic lens enclosed in the testing apparatus. Thefemale bottom 200 has aconcave portion 210 and aseating ridge 212 that is sized to mate with the male top when the testing apparatus is closed. Theconcave portion 210 contains several apertures to permit solution to reach enclosed ophthalmic lenses. - Even though the concave and convex portions of the testing device are illustrated with apertures and radial openings, either piece can contains such openings, or any other suitable openings.
FIG. 3 illustrates thatholder 114 is adapted to connect to ashaft 118. This shaft is connected to a motor that rotates the testing apparatus in solutions. In the preferred methods of the invention, the testing apparatuses are rotated during diffusion testing. - In order to illustrate the invention the following examples are included. These examples do not limit the invention. They are meant only to suggest a method of practicing the invention. Those knowledgeable in contact lenses as well as other specialties may find other methods of practicing the invention. However, those methods are deemed to be within the scope of this invention.
- To prepare 1000 g of a 25 μg/mL ketotifen fumarate (“K-25:
- 1. 9.10 g of boric acid
- 2. 1.00 g of sodium borate decahydrate
- 3. 8.30 g of sodium chloride
- 4. 0.10 g of Ca2DTPA
- 5. 981.475 g of deionized water
- 6. 0.025 g of ketotifen fumarate
- The system is maintained at room temperature throughout the solution making process. All components 1-6 are added in any order and stirred using a magnetic or mechanical stirrer until the solution is homogeneous. Ketotifen fumarate is added last and the mixture is stirred for an additional 30 minutes or as long as it takes to make the solution homogeneous.
- 1-Day Acuvue® Brand Contact Lenses (etafilcon A +3.00) were removed from their packages and repackaged in glass vials containing 3.0 mL of the 25 μg/mL ketotifen fumarate solutions described above to produce K-Lens 25. The vials were sealed with PTFE coated rubber stoppers and heated for 18 minutes at 124° C.
- A lens of Example 1 was placed in a chamber of
FIG. 1 with 1 mL of packaging solution (ingredients 1-5 of Example 1 in the same proportions) that does not contain ketotifen. UV-VIS spectrometer readings were taken at 299 nm at one minute intervals and plotted to determine the dissolution rate of ketotifen from the lens. - A 1-Day Acuvue® Brand Contact Lens was placed in a chamber of
FIG. 1 with 1 mL of the 25 μg/mL ketotifen fumarate of Example 1. UV-VIS spectrometer readings were taken at 299 nm at one minute intervals and plotted to determine the uptake rate of ketotifen to the lens.
Claims (24)
1. (canceled)
2. (canceled)
3. (canceled)
4. (canceled)
5. (canceled)
6. (canceled)
7. (canceled)
8. (canceled)
9. (canceled)
10. (canceled)
11. (canceled)
12. (canceled)
13. (canceled)
14. (canceled)
15. (canceled)
16. (canceled)
17. (canceled)
18. (canceled)
19. A method of measuring the discharge rate of a pharmaceutical agent from an ophthalmic lens, wherein the method comprises the steps of
(a) placing said ophthalmic lens comprising said pharmaceutical agent a testing apparatus, wherein said testing apparatus is sized to enclose said ophthalmic lens and to permit solutions to contact said ophthalmic lens,
(b) placing said enclosed ophthalmic lens into a sufficient amount of solutions,
(c) monitoring sufficient amount of solution to determine the presence or absence of said pharmaceutical agent in said solution
20. The method of claim 19 wherein the sufficient amount of solution is about 25 mL.
21. The method of claim 19 wherein the pharmaceutical agent is selected from the group consisting of ketotifen, ketotifen, nor ketotifen, 11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde, olapatadine, and pharmaceutically acceptable salts and mixtures thereof.
22. The method of claim 19 wherein the ophthalmic lens is selected from the group consisting of acofilcon A, alofilcon A, alphafilcon A, amifilcon A, astifilcon A, atalafilcon A, balafilcon A, bisfilcon A, bufilcon A, comfilcon, crofilcon A, cyclofilcon A, darfilcon A, deltafilcon A, deltafilcon B, dimefilcon A, drooxifilcon A, epsifilcon A, esterifilcon A, etafilcon A, focofilcon A, galfilcon A, genfilcon A, govafilcon A, hefilcon A, hefilcon B, hefilcon D, hilafilcon A, hilafilcon B, hioxifilcon B, hioxifilcon C, hixoifilcon A, hydrofilcon A, lenefilcon A, licryfilcon A, licryfilcon B, lidofilcon A, lidofilcon B, lotrafilcon A, lotrafilcon B, mafilcon A, mesifilcon A, methafilcon B, mipafilcon A, nelfilcon A, netrafilcon A, ocufilcon A, ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, ofilcon A, omafilcon A, oxyfilcon A, pentafilcon A, perfilcon A, pevafilcon A, phemfilcon A, polymacon, senofilcon A, silafilcon A, siloxyfilcon A, tefilcon A, tetrafilcon A, trifilcon A, vifilcon, and xylofilcon A.
23. The method of claim 19 wherein monitoring comprises analyzing the solution by UV Visible Spectroscopy.
24. The method of claim 23 wherein the ophthalmic lens is etafilcon A and the pharmaceutical agent is selected from the group consisting of ketotifen, ketotifen, nor ketotifen, 11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde, olapatadine, and pharmaceutically acceptable salts and mixtures thereof.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/034,522 US20110139995A1 (en) | 2006-10-31 | 2011-02-24 | Methods and devices to test diffusion rates of ocular drug delivery systems |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86358706P | 2006-10-31 | 2006-10-31 | |
US11/930,597 US7918125B2 (en) | 2006-10-31 | 2007-10-31 | Methods and devices to test diffusion rates of ocular drug delivery systems |
US13/034,522 US20110139995A1 (en) | 2006-10-31 | 2011-02-24 | Methods and devices to test diffusion rates of ocular drug delivery systems |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/930,597 Division US7918125B2 (en) | 2006-10-31 | 2007-10-31 | Methods and devices to test diffusion rates of ocular drug delivery systems |
Publications (1)
Publication Number | Publication Date |
---|---|
US20110139995A1 true US20110139995A1 (en) | 2011-06-16 |
Family
ID=39344997
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/930,597 Expired - Fee Related US7918125B2 (en) | 2006-10-31 | 2007-10-31 | Methods and devices to test diffusion rates of ocular drug delivery systems |
US13/034,522 Abandoned US20110139995A1 (en) | 2006-10-31 | 2011-02-24 | Methods and devices to test diffusion rates of ocular drug delivery systems |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/930,597 Expired - Fee Related US7918125B2 (en) | 2006-10-31 | 2007-10-31 | Methods and devices to test diffusion rates of ocular drug delivery systems |
Country Status (11)
Country | Link |
---|---|
US (2) | US7918125B2 (en) |
EP (1) | EP2083793A2 (en) |
JP (1) | JP2010508122A (en) |
KR (1) | KR20090106463A (en) |
CN (1) | CN101573102B (en) |
AR (1) | AR063751A1 (en) |
AU (1) | AU2007313875A1 (en) |
CA (1) | CA2668273A1 (en) |
RU (1) | RU2431468C2 (en) |
TW (1) | TW200835909A (en) |
WO (1) | WO2008055032A2 (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7793535B2 (en) * | 2006-10-31 | 2010-09-14 | Johnson & Johnson Vision Care, Inc. | Devices and methods to simulate an ocular environment |
US8815182B2 (en) * | 2010-11-03 | 2014-08-26 | Agilent Technologies, Inc. | Apparatus and method for holding a contact lens during in vitro testing |
CA2846078C (en) * | 2011-08-31 | 2019-05-28 | Johnson & Johnson Vision Care, Inc. | Method of treating an ophthalmic lens forming optic |
TWI641892B (en) * | 2016-09-30 | 2018-11-21 | 星歐光學股份有限公司 | Contact lens and contact lens product |
CN108872405B (en) * | 2017-05-11 | 2021-06-01 | 武汉先路医药科技股份有限公司 | HPLC analysis detection method for relative substances of lodoxylamine tromethamine |
Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0674893A (en) * | 1992-08-28 | 1994-03-18 | Kakuji Tojo | Circulation type cornea transmission experimental device |
US5627071A (en) * | 1993-09-09 | 1997-05-06 | Copan Italia S.P.A. | Device for sample collection and in vitro transport, mainly for diagnostic use |
US5817924A (en) * | 1998-01-21 | 1998-10-06 | Modern Controls, Inc. | Method and apparatus for measuring oxygen transmission through contact lenses |
US5849811A (en) * | 1994-09-06 | 1998-12-15 | Ciba Vision Corporation | Extended wear ophthalmic lens |
US20010006968A1 (en) * | 1999-12-23 | 2001-07-05 | Julian Trimming | Use of ophthalmic agent |
US6298713B1 (en) * | 2000-05-10 | 2001-10-09 | Bausch & Lomb Incorporated | Method for determination of water transport in biocompatible materials |
US20030024829A1 (en) * | 2001-05-23 | 2003-02-06 | Yasuo Matsuzawa | Basket for holding a medical device |
US20030103201A1 (en) * | 2001-11-30 | 2003-06-05 | Frumusa Gerald F. | Ophthalmic article inspection system |
WO2003053480A1 (en) * | 2001-12-20 | 2003-07-03 | Bausch & Lomb Incorporated | Composition for treating contact lenses in the eye |
JP2005104970A (en) * | 2003-09-10 | 2005-04-21 | Rohto Pharmaceut Co Ltd | Composition for contact lens |
US20050260249A1 (en) * | 2000-12-21 | 2005-11-24 | Neely Frank L | Antimicrobial contact lenses and methods for their production |
US6981403B2 (en) * | 2003-10-31 | 2006-01-03 | Mocon, Inc. | Method and apparatus for measuring gas transmission rates of deformable or brittle materials |
US20060177483A1 (en) * | 2005-02-04 | 2006-08-10 | Byrne Mark E | Contact drug delivery system |
US20080100795A1 (en) * | 2006-10-31 | 2008-05-01 | Dubey Dharmesh K | Devices and methods to simulate an ocular environment |
US20080233006A1 (en) * | 2005-02-25 | 2008-09-25 | The University Of Akron | Method and Apparatus For Determining the Oxygen Permeability of a Polymer |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5115056A (en) | 1989-06-20 | 1992-05-19 | Ciba-Geigy Corporation | Fluorine and/or silicone containing poly(alkylene-oxide)-block copolymers and contact lenses thereof |
US5374662A (en) | 1993-03-15 | 1994-12-20 | Bausch & Lomb Incorporated | Fumarate and fumaramide siloxane hydrogel compositions |
TW585882B (en) * | 1995-04-04 | 2004-05-01 | Novartis Ag | A method of using a contact lens as an extended wear lens and a method of screening an ophthalmic lens for utility as an extended-wear lens |
JP2001518061A (en) * | 1995-12-07 | 2001-10-09 | ボシュ アンド ロム インコーポレイテッド | Monomer units useful for reducing the modulus of silicone hydrogels |
US5998498A (en) * | 1998-03-02 | 1999-12-07 | Johnson & Johnson Vision Products, Inc. | Soft contact lenses |
US6087415A (en) * | 1998-06-11 | 2000-07-11 | Johnson & Johnson Vision Care, Inc. | Biomedical devices with hydrophilic coatings |
JP2000016905A (en) | 1998-07-01 | 2000-01-18 | Tokuriki Kagaku Kenkyusho:Kk | Antibacterial-fungal agent and antibacterial-fungal material |
US6764651B2 (en) * | 2001-11-07 | 2004-07-20 | Varian, Inc. | Fiber-optic dissolution systems, devices, and methods |
US8273366B2 (en) * | 2002-06-05 | 2012-09-25 | University Of Florida Research Foundation, Incorporated | Ophthalmic drug delivery system |
US7380737B2 (en) * | 2006-03-22 | 2008-06-03 | Duo Yeu Metal. Col, Ltd. | Electric seasoning mill |
-
2007
- 2007-10-24 AU AU2007313875A patent/AU2007313875A1/en not_active Abandoned
- 2007-10-24 RU RU2009120580/15A patent/RU2431468C2/en not_active IP Right Cessation
- 2007-10-24 WO PCT/US2007/082335 patent/WO2008055032A2/en active Application Filing
- 2007-10-24 CA CA002668273A patent/CA2668273A1/en not_active Abandoned
- 2007-10-24 EP EP07844557A patent/EP2083793A2/en not_active Withdrawn
- 2007-10-24 JP JP2009535396A patent/JP2010508122A/en not_active Abandoned
- 2007-10-24 KR KR1020097010992A patent/KR20090106463A/en not_active Application Discontinuation
- 2007-10-24 CN CN2007800489730A patent/CN101573102B/en not_active Expired - Fee Related
- 2007-10-30 TW TW096140678A patent/TW200835909A/en unknown
- 2007-10-31 US US11/930,597 patent/US7918125B2/en not_active Expired - Fee Related
- 2007-10-31 AR ARP070104837A patent/AR063751A1/en not_active Application Discontinuation
-
2011
- 2011-02-24 US US13/034,522 patent/US20110139995A1/en not_active Abandoned
Patent Citations (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0674893A (en) * | 1992-08-28 | 1994-03-18 | Kakuji Tojo | Circulation type cornea transmission experimental device |
US5627071A (en) * | 1993-09-09 | 1997-05-06 | Copan Italia S.P.A. | Device for sample collection and in vitro transport, mainly for diagnostic use |
US6951894B1 (en) * | 1994-09-06 | 2005-10-04 | Ciba Vision Corporation | Extended wear ophthalmic lens |
US5849811B1 (en) * | 1994-09-06 | 2000-11-14 | Ciba Vision Corporatin | Extended wear ophthalmic lens |
US5849811A (en) * | 1994-09-06 | 1998-12-15 | Ciba Vision Corporation | Extended wear ophthalmic lens |
US5817924A (en) * | 1998-01-21 | 1998-10-06 | Modern Controls, Inc. | Method and apparatus for measuring oxygen transmission through contact lenses |
US20010006968A1 (en) * | 1999-12-23 | 2001-07-05 | Julian Trimming | Use of ophthalmic agent |
US6395756B2 (en) * | 1999-12-23 | 2002-05-28 | Novartis Ag | Use of ophthalmic agent |
US6298713B1 (en) * | 2000-05-10 | 2001-10-09 | Bausch & Lomb Incorporated | Method for determination of water transport in biocompatible materials |
US20050260249A1 (en) * | 2000-12-21 | 2005-11-24 | Neely Frank L | Antimicrobial contact lenses and methods for their production |
US20030024829A1 (en) * | 2001-05-23 | 2003-02-06 | Yasuo Matsuzawa | Basket for holding a medical device |
US20030103201A1 (en) * | 2001-11-30 | 2003-06-05 | Frumusa Gerald F. | Ophthalmic article inspection system |
WO2003053480A1 (en) * | 2001-12-20 | 2003-07-03 | Bausch & Lomb Incorporated | Composition for treating contact lenses in the eye |
JP2005104970A (en) * | 2003-09-10 | 2005-04-21 | Rohto Pharmaceut Co Ltd | Composition for contact lens |
US6981403B2 (en) * | 2003-10-31 | 2006-01-03 | Mocon, Inc. | Method and apparatus for measuring gas transmission rates of deformable or brittle materials |
US20060177483A1 (en) * | 2005-02-04 | 2006-08-10 | Byrne Mark E | Contact drug delivery system |
US20080233006A1 (en) * | 2005-02-25 | 2008-09-25 | The University Of Akron | Method and Apparatus For Determining the Oxygen Permeability of a Polymer |
US20080100795A1 (en) * | 2006-10-31 | 2008-05-01 | Dubey Dharmesh K | Devices and methods to simulate an ocular environment |
Non-Patent Citations (1)
Title |
---|
Morrison et al., "Permeability of Hydrophilic Contact Lenses", Investigative Opthamology, Jan. 1972 * |
Also Published As
Publication number | Publication date |
---|---|
CN101573102A (en) | 2009-11-04 |
US7918125B2 (en) | 2011-04-05 |
KR20090106463A (en) | 2009-10-09 |
TW200835909A (en) | 2008-09-01 |
CN101573102B (en) | 2012-05-09 |
US20080190221A1 (en) | 2008-08-14 |
RU2009120580A (en) | 2010-12-10 |
RU2431468C2 (en) | 2011-10-20 |
WO2008055032A3 (en) | 2008-08-21 |
JP2010508122A (en) | 2010-03-18 |
CA2668273A1 (en) | 2008-05-08 |
EP2083793A2 (en) | 2009-08-05 |
WO2008055032A2 (en) | 2008-05-08 |
AU2007313875A1 (en) | 2008-05-08 |
AR063751A1 (en) | 2009-02-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10045975B2 (en) | Methods and ophthalmic devices used in the treatment of ocular allergies | |
US20110139995A1 (en) | Methods and devices to test diffusion rates of ocular drug delivery systems | |
US20100300182A1 (en) | Devices and methods to simulate an ocular environment | |
AU2007305205B2 (en) | Methods and ophthalmic devices used in the treatment of ocular allergies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO PAY ISSUE FEE |