Ocular drug delivery devices
A method of forming an ocular delivery device includes exposing a solid, shaped cellulose polymer to a solution including an active pharmaceutical ingredient (API) and a solvent capable of solubilizing the API, wherein the polymer absorbs at least a portion of the solution, including the API and solvent. The method may further include removing at least a portion of the absorbed solvent from the polymer by allowing the absorbed solvent to evaporate from the polymer or by drying the polymer. A variety of cellulose polymers may be used, including hydroxypropyl cellulose. A variety of APIs may be used, including Cyclosporine, Tobramycin and Vancomycin. Ocular delivery devices prepared by the methods may be used to treat a variety of eye disorders.
1. A method of forming an ocular delivery device comprising:
placing a solid, shaped cellulose polymer in a vessel adapted to restrict the swelling of the polymer in at least one direction;
exposing the solid, shaped cellulose polymer, while in said vessel, to a solution comprising an active pharmaceutical ingredient and a solvent capable of solubilizing said active pharmaceutical ingredient, wherein the polymer absorbs at least a portion of the solution, including the active pharmaceutical ingredient and solvent;
allowing the absorbed solvent to evaporate from the polymer or drying the polymer; and
freeing the polymer from the vessel.
2. The method of claim 1 , wherein the at least one direction is a radial direction.
3. The method of claim 1 , wherein the shape and dimension of an interior surface of the vessel substantially matches the shape and dimension of an exterior surface of the polymer.
4. The method of claim 1 , wherein the interior surface of the vessel is coated with a surface-release agent.
5. The method of claim 1 , wherein the ocular delivery device is capable of releasing the active pharmaceutical ingredient upon exposure of the ocular delivery device to a medium.
6. The method of claim 5 , wherein the release of the active pharmaceutical ingredient from the ocular delivery device is substantially zero-order from about two to about six hours after exposing the ocular delivery device to the medium.
7. The method of claim 1 , comprising drying the polymer under vacuum.
8. The method of claim 1 , wherein the polymer is selected from hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, or a mixture of any two or more thereof.
9. The method of claim 1 , wherein the active pharmaceutical ingredient is thermally unstable above about 80° C.
10. The method of claim 1 , wherein the active pharmaceutical ingredient is selected from the group consisting of Acebutolol, Acyclovir, Betaxolol, Bimatoprost, Brimonidine Tartrate, Brinzolamide, Bromfenac Sodium, Cefazolin, Cephalexin, Cephadroxil, Ciprofloxacin, Ciprofloxacin HCl, Cyclosporine, Dexamethasone, Dorzolamide HCl, Epinastine HCl, Erythromycin, Gancicylovir, Gatifloxacin, Gentamicin Sulfate, Ketorolac Tromethamine, Labetalol, Latanoprost, Loteprednol Etabonate, Moxifloxacin HCl, Nepafenac, Ofloxacin, Olopatadine HCl, Penicillin, Pindolol, Prednisolone, Propanolol, Polymyxin B Sulfate/Trimethoprim Sulfate, Sulfacetamide Sodium, Timolol Maleate, Triflourodine, Tobramycin, Travoprost, Vancomycin, Azelastine HCl, Atropine sulfate, Betamethasone, Carbachol, Pheniramine, Cromolyn sodium, Cyclopentolate, Demecarium bromide, Dexamethasone 21-phosphate, Erythromycin Base, Fluorometholone, Gatifloxacin, Homatropine, Hydroxyamphetamine, Idoxuridine, Medrysone, Methylprednisolone, Naphazoline, Resolvins, Phospholipids, Phenylephrine, Phospholine iodide, Prednisolone Acetate, Prednisolone Sodium Sulfate, Sulfisoxazole, Tetrahydrazoline HCl, Timolol, Tobramycin Sulfate, Tropicamide, 6-hydroxy-2-sulfamoylbenzo[b]thiophene, 6-acetoxy-2-sulfamoylbenzo[b]thiophene, 5,6-dihydro-4H-4-hydroxythieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide, and mixtures of any two or more thereof.
11. The method of claim 1 , wherein the solid, shaped cellulose polymer is in the shape of
a half-cylinder, and the vessel comprises a trough; and wherein the trough maintains the shape of the half-cylinder during the exposing.
12. The method of claim 11 , wherein the half-cylinder has a proximal end, a distal end, a diameter of about 0.5 mm to about 4 mm and a length of about 0.5 mm to about 7 mm.
13. The method of claim 11 , wherein the half-cylinder has a surface area to volume ratio greater than about 4 mm 2 :mm 3 .
14. The method of claim 11 , wherein the half-cylinder has a surface area to volume ratio of about 5 mm 2 :mm 3 to about 6 mm 2 :mm 3 .
15. The method of claim 1 , wherein the active pharmaceutical ingredient is Vancomycin or a mixture of Vancomycin and Tobramycin.
16. The method of claim 1 , wherein the active pharmaceutical ingredient is Cyclosporine.
17. The method of claim 1 , wherein the polymer comprises more than 30 wt % hydroxypropyl cellulose.
18. The method of claim 1 , wherein the polymer consists essentially of hydroxypropyl cellulose.
19. The method of claim 1 , wherein the solvent comprises ethanol.
20. The method of claim 1 , wherein the solid, shaped, cellulose polymer has a length from about 1 mm to 7 mm and a width from about 1 mm to 4 mm.