Cyclosporin pro-dispersion liposphere formulation.
OBJECTIVE
Preparation and characterization of an oral pro-dispersion liposphere formulation for cyclosporin, a water insoluble drug with limited bioavailability.


METHODS
Pro-dispersion formulation consisted of a solid fat, dispersing agents and amphiphilic solvents as the major components besides cyclosporin A (CsA) were prepared in the present work. For preparation of this formulation, phospholipid was dissolved in pharmaceutically acceptable water soluble organic solvent, thereafter CsA along with other components was added and formulation optimization was carried out. After formulation preparation, particle size determination and in vitro release study was carried out. Additionally, ultracentrifugation, TEM, Cryo-TEM and DSC techniques were used for in vitro characterization of formulation. The prepared system was also compared with marketed Neoral® microemulsion formulation.


RESULTS
Liposphere formulations were prepared and optimized as according to procedure. Though, determination of in vitro characteristics of such formulations is complex and difficult, yet selected and performed tests confirmed formation and existence of solid liposphere particles upon dispersion of formulation in water. It was also observed that particle size is influenced by the type of solid fat used and amphiphilic solvent present in the formulation. Prepared pro-dispersion was found to be stable for 2 years under normal storage conditions.


CONCLUSIONS
Prepared pro-dispersion liposphere formulation is a homogeneous solution of a lipophilic drug such as cyclosporin in a mixture of surfactants, lipids and ethyl lactate proved to spontaneously form dispersion when added to aqueous media. This formulation concept has a potential clinical use for improved bioavailability of water insoluble drugs.
Department of Medicinal Chemistry, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Avi
A
Avramoff
Wahid
W
Khan
Aviva
A
Ezra
Anna
A
Elgart
Amnon
A
Hoffman
Abraham J
AJ
Domb
D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D020285:Cryoelectron Microscopy; D016572:Cyclosporine / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D014280:Triglycerides / Q000737:chemistry*
D004337:Drug Carriers; D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine