DELIVERY OF DRY FORMULATIONS OF OCTREOTIDE
Methods and devices are described for delivering octreotide to a patient, comprising implanting a controlled release composition for delivering octreotide, wherein the composition does not require hydration prior to implantation, and wherein the composition optionally comprises a release agent.
1 . A method of delivering octreotide to a subject with a substantially zero-order release profile over an extended period of time, but no less than about six months, the method comprising:
subcutaneously implanting in the subject at least one implantable device;
wherein:
the at least one implantable device comprises
a composition comprising octreotide encased in a hydrophilic polymer; and
the implantable device is implanted in a dry state, such that the subject receives on a daily basis over a period of at least about six months dose amounts of octreotide, which are effective to treat the subject.
2 . The method of claim 1 , wherein the hydrophilic polymer comprises a copolymer obtained from the co-polymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers
3 . The method of claim 1 , wherein the hydrophilic polymer comprises one or more methacrylate-based polymers.
4 . The method of claim 1 , wherein the hydrophilic polymer comprises a hydrophilic polyurethane.
5 . The method of claim 1 , wherein the octreotide is in free form, salt form or in the form of a complex thereof.
6 . The method of claim 1 , wherein the octreotide is octreotide acetate.
7 . The method of claim 1 , wherein the subject is afflicted with a GH or IGF-1 hormone disorder or its symptoms.
8 . The method of claim 7 , wherein the GH or IGF-1 disorder is acromegaly.
9 . The method of claim 1 , wherein the subject receives octreotide at an average rate ranging from about 75 μg per day to about 300 μg per day over a period of at least about six months.
10 . The method of claim 1 , wherein the dose amounts of octreotide received by the subject result in octreotide serum levels ranging from about 0.5 ng/ml to about 2 ng/ml.
11 . The method of claim 1 , wherein the subject receives an effective amount of octreotide for a period of at least about twelve months.
12 . The method of claim 1 , wherein the dose amounts of octreotide received by the subject result in octreotide serum levels ranging from about 0.8 ng/ml to about 1.8 ng/ml.
13 . The method of claim 1 , wherein the dose amounts of octreotide received by the subject result in C max for octreotide serum levels below about 1.3 ng/ml.
14 . The method of claim 1 , wherein the dose amounts of octreotide received by the subject result in C max for octreotide serum levels below about 1.0 ng/ml.
15 . The method of claim 1 , wherein release of octreotide occurs at least three to about ten days after implantation.
16 . The method of claim 1 , wherein the subject is afflicted with a condition selected from the group consisting of: carcinoid syndrome, VIPomas, neuroendocrine tumors, proliferative diabetic retinopathy, rosacea, pancreatitis, gastrointestinal bleeding, pancreatic and intestinal fistulas, Graves-Basedow ophthalmopathy, glaucoma, and symptoms associated with chemotherapy or AIDS.
17 . The method of claim 2 , wherein the hydrophilic, ethylenically unsaturated monomers are selected from 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate monomers.
18 . The method of claim 2 , wherein the copolymer comprises about 20% of 2-hydroxyethyl methacrylate and about 80% hydroxypropyl methacrylate.