Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

A method for delivering a peptide analog of luteinizing hormone releasing hormone (LHRH) selected from the group consisting of triptorelin, leuprolide, goserelin, buserelin and cetrorelix at a modulated rate to a subject to whom a plurality of microcapsules containing said peptide analog are administered, said method comprising:

• (a) forming a plurality of microcapsules containing the peptide analog by
• (i) dissolving a polymer selected from a polylactic acid polymer or a lactic co-glycolic copolymer and triethyl citrate in a solvent in which said polymer and said triethyl citrate are soluble to form a solution;
• (ii) adding the peptide analog to the solution to form a peptide suspension in said solution;
• (iii) adding an alkyl derivative to the solution to produce deposition of the polymer and the triethyl citrate on the peptide analog;
• (iv) adding the suspension obtained in step (ii) to a solution in which said polymer and triethyl citrate are not soluble to harden and precipitate microcapsules thus formed;
• and
• (v) isolating the microcapsules thus formed,
• wherein the polymer incorporates triethyl citrate as an additive, wherein the triethyl citrate is added in a range of between 2.7% and 4.4% by total weight of the microcapsule components, and
• (b) administering a sufficient amount of said microcapsules containing the peptide analog to provide a therapeutic effect to said subject, wherein the triethyl citrate produces a modulation of the release of the peptide analog from the microcapsules and a reduction of the initial release rate of the peptide analog from the microcapsules as compared to an identical microcapsule in the absence of triethyl citrate.

A microcapsule comprising:

• i. a peptide analog selected from leuprolide, octreotide or triptorelin;
• ii. a polymer selected from a polylactic acid polymer or a lactic-co-glycolic copolymer containing the peptide analog;
• and
• iii. triethyl citrate;
• wherein the polymer incorporates triethyl citrate as an additive, wherein the triethyl citrate is added in a range of between 2.7% and 4.4% by total weight of the microcapsule components and wherein the triethyl citrate produces a modulation of the release of the peptide analog from the microcapsules and a reduction of the initial release rate of the peptide analog from the microcapsules as compared to an identical microcapsule in the absence of triethyl citrate.