Porous drug matrices and methods of manufacture thereof

Abstract

Drugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution and hydrophilic or hydrophobic excipients that stabilize the drug and inhibit crystallization, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. Hydrophobic or hydrophilic excipients may be selected to stabilize the drug in crystalline form by inhibiting crystal growth or to stabilize the drug in amorphous form by preventing crystallization. The pore forming agent can be either a volatile liquid that is immiscible with the drug solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. The resulting porous matrix has a faster rate of dissolution following administration to a patient, as compared to non-porous matrix forms of the drug. In a preferred embodiment, microparticles of the porous drug matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration.

1 - 21 . (Canceled)  
     
     
         22 . A method of delivering a drug to a patient in need thereof, comprising 
 administering to the patient a therapeutically or prophylactically effective amount of the drug in a formulation comprising at least one hydrophilic or hydrophobic excipient and microparticles of a drug, wherein the microparticles have a mean diameter between about 0.1 and 5 μm and a total surface area greater than about 0.5 m 2 /mL, and wherein the dry porous matrix is in a dry powder form having a TAP density less than or equal to 1.0 g/mL and having a total surface area of greater than or equal to 0.2 m 2 /g.    
     
     
         23 . The method of  claim 22  wherein the matrix comprises between 1 and 95% drug by weight in combination with at least one hydrophilic or hydrophobic excipient which enhances the rate of drug dissolution and stabilizes the drug in crystalline form by inhibiting crystal growth or stabilizes the drug in amorphous form by preventing crystallization.  
     
     
         24 . The method of  claim 22  wherein the formulation is suitable for administration by a route selected from the group consisting of parenteral, mucosal, oral, and topical administration.  
     
     
         25 . The method of  claim 24  wherein the parenteral route is selected from the group consisting of intraveneous, intraarterial, intracardiac, intrathecal, intraosseous, intraarticular, intrasynovial, intracutaneous, subcutaneous, and intramuscular administration.  
     
     
         26 . The method of  claim 24  wherein the mucosal route is selected from the group consisting of pulmonary, buccal, sublingual, intranasal, rectal, and vaginal administration.  
     
     
         27 . The method of  claim 24  wherein the formulation is suitable for intraocular or conjunctival administration.  
     
     
         28 . The method of  claim 24  wherein the formulation is suitable for intracranial, intralesional, or intratumoral administration.  
     
     
         29 . The method of  claim 24  wherein the formulation is in an aqueous solution or suspension suitable for parenteral administration.  
     
     
         30 . The method of  claim 24  wherein the formulation is in a tablet or capsule suitable for oral administration.  
     
     
         31 . The method of  claim 24  wherein the formulation is in a suppository suitable for vaginal or rectal administration.  
     
     
         32 . The method of  claim 24  wherein the formulation is a dry powder suitable for pulmonary administration.  
     
     
         33 . The method of claims  24  wherein the formulation is in a cream or ointment suitable for topical administration.