US 12,233,133 B2
Preparation of solid cyclodextrin complexes for ophthalmic active pharmaceutical ingredient delivery
Thorsteinn Loftsson, Reykjavik (IS); and Zoltán Fülöp, Budapest (HU)
Assigned to Oculis Operations Sàrl, Lausanne (CH)
Filed by Oculis Operations Sàrl, Lausanne (CH)
Filed on Nov. 22, 2023, as Appl. No. 18/517,529.
Application 18/517,529 is a continuation of application No. 17/955,064, filed on Sep. 28, 2022, abandoned.
Application 17/955,064 is a continuation of application No. 17/487,354, filed on Sep. 28, 2021, granted, now 11,491,240, issued on Nov. 8, 2022.
Application 17/487,354 is a continuation of application No. 15/826,247, filed on Nov. 29, 2017, granted, now 11,135,311, issued on Oct. 5, 2021.
Claims priority of provisional application 62/427,737, filed on Nov. 29, 2016.
Prior Publication US 2024/0091377 A1, Mar. 21, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/69 (2017.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 9/10 (2006.01); A61K 9/14 (2006.01); A61K 9/50 (2006.01); A61K 9/51 (2006.01); A61K 31/4184 (2006.01); A61K 31/573 (2006.01); A61K 47/02 (2006.01); A61K 47/10 (2017.01); A61K 47/12 (2006.01); A61K 47/18 (2017.01); A61K 47/34 (2017.01); A61K 47/38 (2006.01); A61P 27/02 (2006.01); A61K 47/40 (2006.01)
CPC A61K 47/6951 (2017.08) [A61K 9/0048 (2013.01); A61K 9/08 (2013.01); A61K 9/10 (2013.01); A61K 9/146 (2013.01); A61K 9/50 (2013.01); A61K 9/51 (2013.01); A61K 31/4184 (2013.01); A61K 31/573 (2013.01); A61K 47/02 (2013.01); A61K 47/10 (2013.01); A61K 47/12 (2013.01); A61K 47/186 (2013.01); A61K 47/34 (2013.01); A61K 47/38 (2013.01); A61P 27/02 (2018.01); A61K 47/40 (2013.01)] 29 Claims
 
1. A topical ophthalmic microsuspension comprising in an ophthalmically acceptable medium:
a solid complex comprising dexamethasone and cyclodextrin,
wherein the cyclodextrin consists of γ-cyclodextrin which is the only cyclodextrin in the microsuspension;
wherein the dexamethasone is the only active agent and is present in the microsuspension at a concentration of about 1% to about 2% by weight based on the volume of the microsuspension (w/v); and
wherein the γ-cyclodextrin is present at a concentration of about 5% to about 20% (w/v);
wherein the solid complex has a diameter D50 from about 1 μm to about 10 μm; and,
wherein the microsuspension comprises a mixture of dexamethasone enol aldehydes at a concentration of less than 0.5% by weight based on the weight of the dexamethasone, wherein the dexamethasone enol aldehydes have the structures:

OG Complex Work Unit Chemistry
wherein the topical ophthalmic microsuspension is obtained by heating to dissolution dexamethasone in an ophthalmically acceptable medium separately from γ-cyclodextrin in a second ophthalmically acceptable medium, cooling and then combining the dexamethasone solution and the γ-cyclodextrin solution to provide the topical ophthalmic microsuspension.