DEPOT FORMULATIONS
Disclosed are formulations and related methods that comprise a non-polymeric, non-water soluble high viscosity liquid carrier material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient or physiological conditions; a specified linear polymer comprising lactide repeat units; and one or more solvents that have a solvent capacity.
1 .- 40 . (canceled)
41 . A method of treating a patient comprising:
injecting the patient with a formulation comprising:
an effective amount of risperidone or a pharmaceutically acceptable salt thereof; and
a vehicle comprising:
(i) sucrose acetate isobutyrate (SAIB) in an amount of from 30 to 65 wt % based on the total weight of the formulation;
(ii) a linear poly(lactide-co-glycolide) in an amount of from 10 to 25 wt % based on the total weight of the formulation, wherein the linear poly(lactide-co-glycolide) possesses a ratio R of lactide repeat units to total repeat units in the linear poly(lactide-co-glycolide), wherein R satisfies the following: 0.55≦R≦0.95, and wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 15,000 Daltons; and
(iii) one or more solvents in an amount greater than 25 wt % based on the total weight of the formulation,
wherein the one or more solvents dissolve the SAIB and the linear poly(lactide-co-glycolide), and wherein the SAIB, linear poly(lactide-co-glycolide), and one or more solvents are monophasic when maintained at approximately 25° C. for a one-week period, and
wherein the method provides controlled delivery of the risperidone or pharmaceutically acceptable salt thereof to the patient.
42 . The method of claim 41 , wherein the one or more solvents comprise ethanol, ethyl lactate, propylene carbonate, glycofurol, N-methylpyrrolidone, 2-pyrrolidone, benzyl benzoate, caprylic/capric triglyceride, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, benzyl alcohol, triacetin, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, 1-dodecylazacycloheptan-2-one, and combinations thereof.
43 . The method of claim 41 , wherein the one or more solvents comprises N-methylpyrrolidone.
44 . The method of claim 41 , wherein the one or more solvents are present in an amount of from 25 to 35 wt % based on the total weight of the formulation.
45 . The method of claim 41 , wherein the SAIB is present in an amount of from 45 to 65 wt % based on the total weight of the formulation.
46 . The method of claim 41 , wherein the SAIB is present in an amount of from 30 to 60 wt % based on the total weight of the formulation.
47 . The method of claim 41 , wherein the SAIB is present in an amount of from 45 to 55 wt % based on the total weight of the formulation.
48 . The method of claim 41 , wherein the linear poly(lactide-co-glycolide) is present in an amount of from 15 to 25 wt % based on the total weight of the formulation.
49 . The method of claim 41 , wherein R satisfies the following: 0.65≦R≦0.95.
50 . The method of claim 41 , wherein R satisfies the following: 0.65≦R≦0.85.
51 . The method of claim 41 , wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 12,500 Daltons.
52 . The method of claim 41 , wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 10,000 Daltons.
53 . The method of claim 41 , wherein the one or more solvents comprises N-methylpyrrolidone, and the one or more solvents are present in an amount of from 25 to 35 wt % based on the total weight of the formulation.
54 . The method of claim 41 , wherein the one or more solvents comprises N-methylpyrrolidone, and wherein the SAIB is present in an amount of from 30 to 60 wt % based on the total weight of the formulation.
55 . The method of claim 41 , wherein the one or more solvents comprises N-methylpyrrolidone, and the linear poly(lactide-co-glycolide) is present in an amount of from 15 to 25 wt % based on the total weight of the formulation.
56 . The method of claim 41 , wherein the one or more solvents comprises N-methylpyrrolidone, and wherein R satisfies the following: 0.65≦R≦0.95.
57 . The method of claim 41 , wherein the one or more solvents comprises N-methylpyrrolidone, and wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 12,500 Daltons.
58 . The method of claim 41 , wherein R satisfies the following: 0.65≦R≦0.95, and wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 12,500 Daltons.
59 . A method of treating a patient comprising:
injecting the patient with a formulation comprising:
an effective amount risperidone or a pharmaceutically acceptable salt thereof; and
a vehicle comprising:
(i) sucrose acetate isobutyrate (SAIB) in an amount of from 30 to 55 wt % based on the total weight of the formulation;
(ii) a linear poly(lactide-co-glycolide) in an amount of from 15 to 25 wt % based on the total weight of the formulation, wherein the linear poly(lactide-co-glycolide) possesses a ratio R of lactide repeat units to total repeat units in the linear poly(lactide-co-glycolide), wherein R satisfies the following: 0.65≦R≦0.85, and wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 12,500 Daltons; and
(iii) N-methylpyrrolidone in an amount of from 25 to 35 wt % based on the total weight of the formulation,
wherein the N-methylpyrrolidone dissolves the SAIB and the linear poly(lactide-co-glycolide), and wherein the SAIB, linear poly(lactide-co-glycolide), and N-methylpyrrolidone are monophasic when maintained at approximately 25° C. for a one-week period
wherein the method provides controlled delivery of the risperidone or pharmaceutically acceptable salt thereof to the patient.
60 . The method of claim 59 , wherein the linear poly(lactide-co-glycolide) has a weight average molecular weight less than or equal to 10,000 Daltons.