Diketopiperazine salts for drug delivery and related methods

A therapeutic composition comprising a pharmaceutically acceptable salt of a heterocyclic compound according to Formula 1:

• wherein R1 or R2 comprise at least one carboxylate functional group;
• E1 and E2 comprise N or O;
• the salt further comprises at least one cation;
• and
• said composition further comprises a biologically active agent.

A method of preparing a solid composition for drug delivery comprising:

• preparing a solution containing a biologically active agent and a pharmaceutically-acceptable salt of a heterocyclic compound in a solvent;
• removing said solvent by a method selected from the group consisting of distillation, evaporation, spray drying and lyophilization;
• wherein said pharmaceutically acceptable salt of a heterocyclic compound has the structure according to Formula 1:
• wherein R1 or R2 comprise at least one carboxylate functional group;
• E1 and E2 comprise N or O;
• and
• said salt further comprises at least one cation.

A method of preparing a dry powder for drug delivery comprising:

• spray drying a solution of a pharmaceutically acceptable salt of a heterocyclic compound and a biologically active agent to form a dry powder;
• wherein the dry powder releases a biologically active agent;
• and
• wherein said pharmaceutically acceptable salt of a heterocyclic compound has the structure according to Formula 1:
• wherein R1 or R2 comprise at least one carboxylate functional group;
• E1 and E2 comprise N or O;
• and
• said salt further comprises at least one cation.

A composition for delivering biologically active agents wherein said composition comprises a pharmaceutically acceptable salt of a heterocyclic compound and a biologically active agent spray dried to form a dry powder such that said dry powder releases said biologically active agents and said pharmaceutically acceptable salt of a heterocyclic compound has the structure according to Formula 1:

• wherein R1 or R2 comprise at least one carboxylate functional group;
• E1 and E2 comprise N or O;
• and
• said salt further comprises at least one cation.

A microparticulate system for drug delivery comprising a composition of pharmaceutically acceptable salt of a heterocyclic compound and a biologically active agent, wherein said composition releases a biologically active agent, and said heterocyclic compound has the structure according to Formula 1:

• wherein R1 or R2 comprise at least one carboxylate functional group;
• E1 and E2 comprise N or O;
• and
• said salt further comprises at least one cation.

A method for delivery of particles to the pulmonary system comprising:

• administering via inhalation to a patient in need of treatment an effective amount of a biologically active agent in the form of a dry powder, said dry powder prepared by spray drying a solution comprising composition of a pharmaceutically acceptable salt of a heterocyclic compound and a biologically active agent;
• wherein said dry powder releases said biologically active agent in the pulmonary system;
• and
• wherein said pharmaceutically acceptable salt of a heterocyclic compound has the structure according to Formula 1:
• wherein R1 or R2 comprise at least one carboxylate functional group;
• E1 and E2 comprise N or O;
• and
• said salt further comprises at least one cation.