CONTROLLED RELEASE FORMULATIONS OF OCTREOTIDE
A formulation of octreotide or pharmaceutically acceptable salts thereof, which provides controlled release of a therapeutically effective amount of octreotide for a period of at least about two months. Methods of treating acromegaly, decreasing growth hormone, decreasing IGP-1, and treating conditions associated with carcinoid tumors and VIPomas by administering a controlled release formulation of octreotide are provided herein.
1 . A method of treating a patient suffering from a condition associated with carcinoid tumors or suffering from one or more symptoms associated with such condition, the method comprising:
implanting subcutaneously into a patient in need thereof at least one implant comprising a hydrophilic polymer and a pharmaceutical formulation comprising octreotide;
wherein the pharmaceutical formulation is contained within the hydrophilic polymer;
wherein the pharmaceutical formulation contains between about 20 to about 150 milligrams of octreotide, in free form or salt form; and
wherein the at least one implant releases a therapeutically effective amount of the octreotide to the patient over a period of at least about two months,
2 . The method of claim 1 , wherein the effective amount of the octreotide provides an in vivo average C SS in the patient of about 0.1 ng/ml to about 9 ng/ml of octreotide.
3 . The method of claim 1 , wherein the pharmaceutical formulation contains from about 40 to about 90 milligrams of octreotide.
4 . The method of claim 1 , wherein the octreotide is octreotide acetate.
5 . The method of claim 4 , wherein the pharmaceutical formulation contains about 50 milligrams of the octreotide acetate.
6 . The method of claim 4 , wherein the pharmaceutical formulation contains about 80 milligrams of the octreotide acetate.
7 . The method of claim 2 , wherein the effective amount of the octreoti de provides an in vivo average C SS in the patient of about I ng/ml to about 2 ng/ml of octreotide.
8 . The method of claim 1 , wherein the at least one implant releases a therapeutically effective amount of octreotide over a period of about two months to about two years.
9 . The method of claim 1 , wherein the at least one implant releases a therapeutically effective amount of the octreotide over about six months.
10 . The method of claim 1 , Wherein the hydrophilic polymer comprises a copolymer of at least two hydrophilic, ethylenically unsaturated monomers.
11 . The method of claim 10 , wherein the at least two hydrophilic, ethylenically unsaturated monomers arc 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate.
12 . The method of claim 10 , wherein the copolymer comprises about 20% of 2-hydroxyethyl methacrylate and about 30% hydroxypropylmethacrylate.
13 . The method of claim 10 , wherein the copolymer comprises about 40% of 2-hydroxyethyl methacrylate and about 60% hydroxypropylmethacrylate.
14 . The method of claim 1 , wherein the hydrophilic polymer comprises a hydrophilic polyurethane.
15 . The method of claim 1 , wherein the pharmaceutical formulation further comprises hydroxypropylcellulose.
16 . The method of claim 15 , wherein the pharmaceutical formulation contains about 0.5 to 20% w/w of the hydroxypropylcellulose
17 . The method of claim 1 , wherein the pharmaceutical formulation further comprises magnesium stearate.
18 . The method of claim 17 , wherein the pharmaceutical formulation contains about 0.5 to 5% w/w of the magnesium stearate.
19 . The method of claim 1 , wherein the at least one implant releases the octreotide at a rate of about 10 ug to about 1000 ug per day over a period of about six months.
20 . The method of claim 1 , wherein the at least one implant is two or more implants.
21 - 23 . (canceled)