All4Nutra
Parenteral administration of Busulfan (BU) conquers the bioavailability and biovariability related issues of oral BU by maintaining the plasma drug concentration in therapeutic range with minimalfluctuations thereby significantly reducing the side effects. Busulfex® is the only commercially available parenteral formulationof BU composed of organic solvents N, N-dimethylacetamide and polyethylene glycol 400. Since, BU is highly susceptible to hydrolytic degradation; Busulfex® has poor physical and chemicalstability in IV fluids. It is quintessential to develop organic solvent free formulation of BU using parenterally acceptable excipients to enhance its solubility and stability in IV fluids. TheProliposomal formulation of BU was prepared by adsorption-sonicaton method using egg phosphotidylcholine, cholesterol, tween 80 and mannitol. Vesicle size and entrapment efficiency were optimizedusing 24 full factorial design and characterized by DSC, PXRD and TEM. Optimized formulation spontaneously forms 74.0±1.7 nm sized nanovesicles with 72.9±1.5 % entrapment efficiency. DSC andPXRD studies revealed that BU was present in phospholipid bilayer in amorphized form and TEM images confirmed the multi lamellar vesicular structure. Physicochemical stability of BU was significantlyenhanced with proliposomal formulation. In-vivo studies in Sprague Dawley rats showed proliposomal formulation has comparable immunosuppression activity and 110.62 % relativebioavailability as compared to marketed Busulfan formulation i.e. Busulfex®.
