Ophthalmic emulsions containing an immunosuppressive agent
Ophthalmic oil-in-water emulsions, which comprises colloid particles having an oily core surrounded by an interfacial film, the emulsion comprising an 10 immunosuppressive agent, an oil, preferably at least 50% of which being MCT, and tyloxapol. Use of such an emulsion for the manufacture of medicament for treatment of eye conditions, particularly of dry eye diseases.
1. An ophthalmic oil-in-water emulsion, which comprises colloid particles having an oily core surrounded by an interfacial film, said emulsion comprising:
0.05 to 0.3% cyclosporine in weight to the total weight (w/w) of the emulsion,
0.5 to 4% w/w medium-chain triglycerides,
0.02% w/w benzalkonium chloride, and
surfactants,
wherein the surfactants consist of a mixture of tyloxapol and poloxamer,
wherein the tyloxapol is present in an amount of 0.3% w/w and the poloxamer is present in an amount of 0.1% w/w, and
wherein said emulsion is cationic,
wherein said emulsion meets zeta potential stability under thermal stress conditions as determined by Test A:
measuring zeta potential, in mV, of said emulsion at the time of preparation is Z 0 ,
sealing 5-10 ml of said emulsion in 10 ml Type I glass vials under nitrogen atmosphere without bubbling,
storing said sealed vials at 80° C. for 7 days,
measuring zeta potential, in mV, of said emulsion at 7 days, Z 7days ,
determining the difference between Z 7days −Z 0 , δA, the emulsion meeting the zeta potential stability under thermal stress conditions according to Test A for a δA less than the 10 mV standard error of zeta potential measurement,
wherein said emulsion does not comprise phospholipids, and
wherein said emulsion does not comprise substances capable of generating a negative charge.
2. The ophthalmic oil-in-water emulsion according to claim 1 , which can be administered topically.
3. The ophthalmic oil-in-water emulsion according to claim 1 , wherein said emulsion comprises 2% w/w of the medium chain triglycerides compared to the total weight of the emulsion.
4. The ophthalmic oil-in-water emulsion according to claim 1 wherein the cyclosporine is or includes cyclosporine A.
5. The ophthalmic oil-in-water emulsion according to claim 1 , further including one or more oils selected from the group consisting of olive, soy, corn, mineral, cottonseed, safflower and sesame.
6. The ophthalmic oil-in-water emulsion according to claim 1 wherein said colloid particles of the emulsion of the invention have an average particle size of equal or less than 1 μm, and its size population distribution is monomodal.
7. The ophthalmic oil-in-water emulsion according to claim 1 wherein said colloid particles of the emulsion of the invention have an average particle size of equal or less than 1 μm.
8. A method for treating a dry eye disease comprising administering an effective amount to a subject in need thereof, the ophthalmic oil-in-water emulsion according to claim 1 .
9. The method according to claim 8 , wherein the dry eye disease is selected from the group consisting of keratoconjunctivis sicca, atopic keratoconjunctivitis sicca and vernal keratoconjunctivitis.