Method of producing a cationic liposomal preparation comprising a lipophilic compound
View Patent ↗A method for producing a cationic liposomal preparation comprising a lipophilic active compound with physical and chemical stability during manufacturing, storing and reconstituting, and further a cationic liposomal preparation obtainable by this method as well as specific cationic liposomal preparations as well as pharmaceutical compositions are disclosed.
1. A cationic liposomal suspension having a pH of between about 3 and 7 and comprising at least one cationic lipid of at least 30 mol %, optionally at least one further amphiphile of up to about 69.9 mol %, a lipophilic active compound of at least 2 mol % and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v), wherein said lipophilic active compound is physically and chemically stable for at least 12 hours at about 2 to 8° C., or at least 4 hours at ambient temperature.
2. The suspension of claim 1 comprising
at least one cationic lipid of at least 30 mol %, optionally at least one further amphiphile of up to about 65 mol %, paclitaxel of about 2 mol % to about 5 mol % and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v), wherein said lipophilic active compound is physically and chemically stable for at least 12 hours at about 2 to 8° C., or at least 4 hours at ambient temperature.
3. The suspension of claim 1 comprising at least one cationic lipid of at least 30 mol %, optionally at least one further amphiphile of up to 65 mol %, docetaxel of at least 5 mol % and a stabilizing agent of about 0.1% (m/v) to about 20% (m/v).
4. The suspension of claim 1 , comprising a stabilizing agent in the range of about 5% (m/v) to about 15% (m/v).
5. The suspension of claim 1 , wherein said liposomal suspension comprises liposomes with an average particle size of about 50 nm to about 400 nm.
6. The suspension of claim 1 , wherein said liposomal suspension comprises liposomes having a positive zeta potential in about 0.05 M KCl solution at about pH 7.5 at room temperature.
7. The suspension of claim 1 , wherein said liposomal suspension comprises less than 5% degradation product of said lipophilic active compound.
8. The suspension of claim 2 , wherein said liposomal suspension comprises less than 5% degradation product of paclitaxel.
9. The suspension of claim 8 , wherein said liposomal suspension comprises less than 5% of 7-Epi-Taxol or Baccatin III.
10. A pharmaceutical composition comprising the suspension of claim 1 , together with a pharmaceutically acceptable carrier, diluent, and/or adjuvant.
11. The suspension of claim 1 , wherein the pH is between about 4.0 and 6.5.
12. The suspension of claim 1 , wherein the lipophilic active agent is a taxane.
13. The suspension of claim 12 , wherein the taxane is selected from the group consisting of paclitaxel, docetaxel, or a lipophilic derivative thereof.
14. A cationic liposomal preparation comprising a dehydrated preparation of the suspension of claim 1 .
15. The suspension of claim 5 , wherein said liposomal suspension comprises liposomes with an average particle size of about 100 nm to about 300 nm.
16. The suspension of claim 11 , wherein the pH is between about 4.5 and 5.5.