LYOPHILIZATION OF LIPOSOME ENCAPSULATED HEMOGLOBIN

VESTAR PROPOSES TO DEVELOP THE METHODS NECESSARY TO LYOPHILIZE LIPOSOME ENCAPSULATED HEMOGLOBIN (IEH) . THE METHODS AND EQUIPMENT UTILIZED WILL BE COMMENSURATE WITH LARGE-SCALE LYOPHILIZATION PRACTICES COMMON TO THE PHARMACEUTICAL INDUSTRY IN FULL ACCORDANCE WITH GOOD MANUFACTURING PRACTICE (GMP) GUIDELINES. PRESENT PRACTICE IN FREEZE-DRYING OF LIPOSOMES CENTERS ON THE USE OF DISACCHARIDES AS A CRYOPROTECTANT. INITIAL WORK WILL FOCUS ON SELECTING THE MOST SUITABLE DISACCHARIDE IN TERMS OF MAINTAINING THE DESIRABLE LIPOSOMAL PROPERTIES OF MEAN DIAMETER, COMPONENT CHEMICAL STABILITY AND HEMOGLOBIN ENCAPSULATION AND SUITABILITY FOR INJECTION IN HUMANS. FOLLOWING, BUT TO SOME EXTENT IN PARALLEL WITH CRYOPROTECTANT SELECTION WORK WILL EMPHASIZE CYCLE PARAMETER IDENTIFICATION USING A SHELF TYPE LYOPHILIZER. THE CONTROLLING PARAMETERS OF FREEZING RATE, FILL HEIGHT, CONTAINER SELECTION, PRIMARY AND SECONDARY DRYING TEMPERATURES AND PRESSURES WILL BE EVALUATED. ANALYTICAL COMPARISON OF PREAND POST-LYOPHILIZATION IEH WILL BE DONE TO DEMONSTRATE THE EFFECTIVENESS OF THE PROPOSED CYCLE. FINAL TESTS WILL BE DONE IN VESTAR'S GMP ASEPTIC FILLING AND LYPHILIZATION COMPLEX UTILIZING STERILE PRODUCT TO DEMONSTRATE POST PROCESS STERILITY. NO IN-VIVA TESTING OF LEH IS PLANNED.