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 process for making a pharmaceutical composition comprising microparticles of crystalline fumaryl diketopiperazine coated with a vasoactive agent comprising:
 (i) dissolving the fumaryl diketopiperazine in a solution;   (ii) obtaining crystalline fumaryl diketopiperazine microparticles in a suspension having a fluid phase;   (iii) dissolving said vasoactive agent in the fluid phase of said suspension;   (iv) increasing the pH of the fluid phase to about 4 to about 5;   (v) adsorbing of said vasoactive agent onto a surfaces of said crystalline fumaryl diketopiperazine microparticles to provide a coating of said vasoactive agent on said crystalline fumaryl diketopiperazine microparticles;   (vi) removing or exchanging said solvent from the suspension;   (vii) forming a dry powder comprising the crystalline fumaryl diketopiperazine microparticles coated with the vasoactive agent.   
     
     
         2 . The process of  claim 1 , further comprising the step of dissolving said vasoactive agent in an alcohol prior to dissolving said vasoactive agent in the fluid phase. 
     
     
         3 . The process of  claim 2 , wherein the alcohol is selected from one or more of the group consisting of: ethanol, methanol, trifluoroethanol and hexafluoroisopropanol. 
     
     
         4 . The process of  claim 2 , wherein the alcohol is ethanol. 
     
     
         5 . The process of  claim 2 , wherein the alcohol is about 5% to about 20% w/v between pH 2.0-4.0 in the suspension.