Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces

Abstract

Methods are provided for promoting the adsorption of an active agent to microparticles by modifying the structural properties of the active agent in order to facilitate favorable association to the microparticle.

What is claimed: 
     
         1 . A pharmaceutical composition comprising microparticles made by a method for making a microparticle coated with an active agent that is of pharmaceutical use, the method comprising:
 (i) obtaining a crystalline fumaryl diketopiperazine microparticle wherein the crystalline diketopiperazine microparticle does not comprise an active agent;   (ii) forming a suspension comprising said crystalline diketopiperazine microparticle and a solvent;   (iii) dissolving said active agent in the fluid phase of said suspension;   (iv) increasing the pH of the fluid phase to about  4  to  5 ;   (v) adsorbing of said active agent onto a surface of said crystalline fumaryl diketopiperazine microparticle to provide a coating of said active agent on said crystalline fumaryl diketopiperazine microparticle; and   (vi) removing or exchanging said solvent after step (v).   
     
     
         2 . A pharmaceutical composition comprising microparticles made by the method of  claim 1 . 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the active agent is a protein, peptide, polypeptide, small molecule, or nucleic acid molecule. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the active agent is glucagon-like peptide 1 (GLP-1). 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the active agent is vasoactive, or anticoagulant. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the active agent is a neuroactive agent. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the active agent is a hormone. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the active agent is an, antibiotic agent, antiviral agent, antigenic agent, immunomodulating agent, cytotoxic agent, or antibody.