Amino acids as cryoprotectants for liposomal delivery systems.
Liposomes provide an efficient delivery system for solubilisation and delivery of both small and macro molecules. However, they suffer from the disadvantage of instability when stored as aqueous dispersions. Cryoprotection of the liposomal systems provides an effective approach to overcome poor stability whilst maintaining formulation characteristics, although, the formulation of a freeze-dried product requires the consideration of not only the selection of an appropriate cryoprotectant, but also needs careful consideration of the processing parameters including pre-freezing conditions, primary and secondary drying protocols along with optimisation of cryoprotectant concentration. This current work investigates the application of amino acids as potential cryoprotectants for the stabilisation of liposomes, and results indicate that amino acids show biphasic nature of stabilisation with 4 mol of cryoprotectant per mole of the lipid exhibiting optimum cryoprotection. The investigations of process parameters showed that the pre-freezing temperatures below the glass transition of the amino acids followed by drying for over 6h resulted in stable formulations. Studies investigating the efficiency of drug retention showed that the cryoprotection offered by lysine was similar to that shown by trehalose, suggesting that amino acids act as effective stabilizers. ESEM analysis was carried out to monitor morphology of the rehydrated liposomes.
Mohammed
Afzal R
AR
Medicines Research Unit, Aston Pharmacy School, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Coombes
Allan G A
AG
Perrie
Yvonne
Y
D000596:Amino Acids / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D003451:Cryoprotective Agents / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D005612:Freeze Drying; D006639:Histidine / Q000737:chemistry; D007052:Ibuprofen / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008239:Lysine / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical; D013696:Temperature; D013997:Time Factors; D014199:Trehalose / Q000737:chemistry; D014783:Viscosity; D014867:Water / Q000737:chemistry
D000596:Amino Acids; D003451:Cryoprotective Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D014867:Water; D006639:Histidine; D001120:Arginine; D002784:Cholesterol; D014199:Trehalose; D008239:Lysine; D007052:Ibuprofen