Claims for Patent: 8,597,680

Summary for Patent: 8,597,680

Title:	Microtablets for drug delivery
Abstract:	Methods and systems are provided for making a drug microtablet. The method includes loading a lyophilization capillary channel with a liquid drug solution; lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; compressing the lyophilized drug formulation in the lyophilization capillary channel, or in a compression capillary channel, to form a microtablet; and ejecting the microtablet from the lyophilization capillary channel or compression capillary channel. The methods and systems may provide drug microtablets having improved content uniformity and reduced weight variability.
Inventor(s):	Coppeta; Jonathan R. (Windham, NH), Dyer; Robert (Concord, MA), Stevenson; Cynthia L. (Mountain View, CA)
Assignee:	On Demand Therapeutics, Inc. (Tyngsboro, MA)
Application Number:	13/672,043
Patent Claims:	1. A plurality of drug microtablets produced by a method which comprises: (i) loading a lyophilization capillary channel with a liquid drug solution; (ii) lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; (iii) compressing the lyophilized drug formulation in the lyophilization capillary channel, or in a compression capillary channel, to form one of the microtablets; (iv) ejecting the microtablet from the lyophilization capillary channel or the compression capillary channel; and (v) repeating steps (i) through (iv) in series or parallel to form a second of the microtablets, wherein the largest dimension of any of the microtablets is from 50 microns to 2000 microns, and wherein the microtablets have (i) an actual weight that deviates less than about 10% from a target weight for each microtablet, (ii) an actual amount of a drug that differs from a target amount of the drug for each microtablet by less than about 25% or (iii) both (i) and (ii). 2. The drug microtablets of claim 1, wherein the largest dimension of any of the microtablets is from 50 microns to 1500 microns. 3. The drug microtablets of claim 1, wherein the largest dimension of any of the microtablets is from 50 microns to 1000 microns. 4. The drug microtablets of claim 1, wherein the largest dimension of any of the microtablets is from 50 microns to 750 microns. 5. The drug microtablets of claim 1, wherein the largest dimension of any of the microtablets is from 50 microns to 500 microns. 6. The drug microtablets of claim 1, wherein the drug comprises a protein, antibody, antibody fragment, vaccine, RNA, or DNA. 7. The drug microtablets of claim 6, wherein the drug comprises an anti-VEGF drug. 8. The drug microtablets of claim 7, wherein the anti-VEGF drug comprises ranibizumab, bevacizumab, or aflibercept. 9. The drug microtablets of claim 1, which have a glassy amorphous matrix phase containing the drug and a combination of lyoprotectant, binding agent, buffer, surfactant, and/or slip agent excipients. 10. The drug microtablets of claim 1, wherein the microtablets have a cylindrical or tapered cylindrical walls. 11. The drug microtablets of claim 1, wherein the actual weight deviates less than about 5% from the target weight for each microtablet. 12. The drug microtablets of claim 1, wherein the actual amount of the drug differs from the target amount of the drug by less than about 15%. 13. The microtablets of claim 12, wherein the target amount of the drug for each microtablet is 100 micrograms. 14. A plurality of drug microtablets produced by a method which comprises: (i) loading a lyophilization capillary channel with a liquid drug solution; (ii) lyophilizing the liquid drug solution in the lyophilization capillary channel to produce a lyophilized drug formulation; (iii) compressing the lyophilized drug formulation using a piston having a concave face fir contacting the lyophilized drug formulation, in the lyophilization capillary channel, or in a compression capillary channel, to form one of the microtablets; (iv) ejecting the microtablet from the lyophilization capillary channel or the compression capillary channel; and (v) repeating steps (i) through (iv) in series or parallel to form a second of the microtablets, wherein the largest dimension of any of the microtablets is from 50 microns to 2000 microns, and wherein the microtablets have a convex end surface formed by the concave face of the piston, and the microtablets have (i) an actual weight that deviates less than about 10% from a target amount of the drug for each microtablet by less than about 25%, or (iii) both (i) and (iii). 15. The drug microtablets of claim 14, Wherein the drug comprises a protein, antibody, antibody fragment, vaccine, RNA, or DNA. 16. The drug microtablets of claim 15, wherein the drug comprises an anti-VEGF drug. 17. The drug microtablets of claim 14, wherein the microtablets further comprise lyoprotectant, binding agent, buffer, surfactant, and/or slip agent excipients. 18. The drug microtablets of claim 14, wherein the actual weight deviates less than about 5% from the target weight for each microtablet. 19. The drug microtablets of claim 14, wherein the actual amount of the drug differs from the target amount of the drug by less than about 15%.

Details for Patent 8,597,680

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2031-09-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	06/30/2006		2031-09-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	08/10/2012		2031-09-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	10/13/2016		2031-09-12
Genentech, Inc.	LUCENTIS	ranibizumab	Injection	125156	03/20/2018		2031-09-12
Regeneron Pharmaceuticals, Inc.	EYLEA	aflibercept	Injection	125387	11/18/2011		2031-09-12
Regeneron Pharmaceuticals, Inc.	EYLEA	aflibercept	Injection	125387	08/16/2018		2031-09-12