Controlled release formulations of octreotide

Abstract

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 IGF-1, and treating conditions associated with carcinoid tumors and VIPomas by administering a controlled release formulation of octreotide are provided herein.

What is claimed is: 
     
         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 fort on 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 viva 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 octreotide provides an in vivo average C ss  in the patient of about 1 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 o at least two hydrophilic, ethylenically unsaturated monomers. 
     
     
         11 . The method of  claim 10 , wherein the at least two hydrophilic, ethylenically unsaturated monomers are 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate. 
     
     
         12 . The method of  claim 10 , wherein the copolymer comprises about 20% of 2-hydroxyethyl methacrylate and about 80% hydrox.ypropylmethacrylate. 
     
     
         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 . The method of  claim 1 , wherein the at least one implant releases the octreotide at a rate of about 30 μg to about 250 μg per day in vitro. 
     
     
         22 . The method of  claim 1 , wherein the at least one implant is implanted in a dry state. 
     
     
         23 . The method of  claim 1 , wherein the at least one implant is implanted in a hydrated state.