Use of liquid medium exchange by cross flow filtration in the preparation of drug suspensions
Disclosed is a method of making particles of a drug wherein use is made of diafiltration. The diafiltration can be with anti-solvent, in which case a precipitate is obtained of particles as such. The diafiltration can also be with a pharmaceutically acceptable suspension medium. In that case several process steps of isolating, drying, transporting of particles can be avoided, because the suspension resulting from the synthesis of the particles is directly turned into a final drug product formulation.
1. A method of making a pharmaceutical composition comprising particles of a drug, wherein the drug is initially produced in the form of a suspension in a first liquid medium, wherein the suspension is subjected to cross-flow filtration against a further liquid medium, said further liquid medium being a pharmaceutically acceptable media capable of retaining the drug as a suspension,
wherein the suspension in the first liquid medium is subjected to cross-flow filtration against a second liquid medium so as to obtain a suspension in the second liquid medium, said suspension in the second liquid medium being subjected to crossflow filtration against the pharmaceutically acceptable liquid medium, wherein the first liquid medium is acetone, a mixture of acetone and water or fractionated vegetable oil, wherein the second liquid medium is acetone, a mixture of acetone and water, fractionated vegetable oil or ethyl oleate, wherein the pharmaceutically acceptable media is paraffin or ethyl oleate; and
wherein when the first liquid medium is acetone, the second liquid medium is not acetone, when the first liquid medium is acetone and water, the second liquid medium is not acetone and water and when the first liquid medium is fractionated vegetable oil, the second liquid medium is not fractionated vegetable oil, and when the second liquid medium is ethyl oleate, the pharmaceutically acceptable media is not ethyl oleate.
2. The method according to claim 1 , wherein the further liquid medium is a pharmaceutically acceptable medium capable of retaining the drug in suspension, and the produced composition comprising particles of a drug is a suspension of the drug in a pharmaceutically acceptable liquid medium.
3. The method according to claim 1 , wherein the second liquid medium is selected from the group consisting of ethyl oleate and fractionated vegetable oil, and the further liquid medium is liquid paraffin.
4. The method of claim 1 , wherein the drug is a cephalosporin antibiotic.
5. The method according to claim 2 , wherein the drug is a cephalosporin antibiotic.
6. The method according to claim 1 , wherein the drug is a cephalosporin antibiotic and the first liquid medium is acetone or a mixture of acetone and water and the pharmaceutically acceptable medium is ethyl oleate.
7. The method according to claim 1 , wherein the drug is a cephalosporin antibiotic and the first liquid medium is fractionated vegetable oil, the second liquid medium is acetone or a mixture of acetone and water and the pharmaceutically acceptable medium is liquid paraffin.
8. The method of claim 1 , wherein the fractionated vegetable oil is capric/caprylic triglycerides or propylene glycol dicaprylate/caprate.
9. The method of claim 3 , wherein the fractionated vegetable oil is capric/caprylic triglycerides or propylene glycol dicaprylate/caprate.
10. The method of claim 7 , wherein the fractionated vegetable oil is capric/caprylic triglycerides or propylene glycol dicaprylate/caprate.