ABSTRACT
Instron Residual Seal Force (IRSF) of 13 mm glass vial/rubber closure systems was determined using an Instron 4501 Materials Testing System and computerized data analysis. A series of three cap anvils varying in shape and dimensions were machined to optimize cap anvil performance. Cap anvils with spherical top surfaces and narrow internal dimensions produced uniform stress-deformation curves from which precise IRSF values were derived.
Subject(s)
Drug Packaging/methods , Glass , Materials Testing , Pressure , Rubber , Technology, PharmaceuticalABSTRACT
Instron Residual Seal Force (IRSF) of glass vial/rubber closure systems was determined using an Instron 4501 Materials Testing System. Computer programs were written to process raw data and calculate IRSF values. Preliminary experiments indicated both the appearance of the stress-deformation curves and precision of the derived IRSF values were dependent on the internal dimensions and top surface geometry of the cap anvil. Therefore, a series of five cap anvils varying in shape and dimensions were machined to optimize performance and precision. Vials capped with West 4416/50 PURCOAT button closures or Helvoet compound 6207 lyophilization closures were tested with each cap anvil. Cap anvils with spherical top surfaces and narrow internal dimensions produced more precise results and more uniform stress-deformation curves than cap anvils with flat top surfaces and wider internal dimensions.
Subject(s)
Computer-Aided Design , Drug Packaging/methods , Electronic Data Processing , Equipment Design , Evaluation Studies as Topic , Freeze Drying , Models, Theoretical , Stress, MechanicalABSTRACT
The thermal inactivation of three endotoxin preparations on the inner surface of glass capillary tubes was studied. The samples were exposed to precisely controlled dry heat conditions at study temperatures ranging from 170 degrees to 350 degrees C, and were assayed using the gel-clot method of the Limulus Amebocyte Lysate test. Plots of the log of the amount of pyrogenic material remaining versus heating time revealed apparently biphasic destruction curves. The initial slopes were linear to a minimum 3-log unit reduction, and were followed by slower destruction rates for the terminal slopes. D values were calculated from the initial slopes of the destruction data, and Z values were estimated from the D values. The D and Z values were found to vary with the initial charged amounts of endotoxin. A second-order equation was found to be an inappropriate model for the inactivation process at temperatures between 170 degrees and 250 degrees C, but was found to be suitable for temperatures between 250 degrees and 325 degrees C. The data were successfully fit to a biexponential equation for all the temperatures studied. The overall inactivation rate of the endotoxin material formulated with fillers was apparently faster than that for the pure endotoxin preparations.
Subject(s)
Endotoxins , Hot Temperature , Sterilization/methods , Escherichia coli , Glass , In Vitro TechniquesABSTRACT
The gel-clot method of the Limulus Amebocyte Lysate (LAL) test was used to determine the recovery efficiency of four different endotoxin preparations from Type I glass capillary tubes. Each capillary tube was charged with 10,000 endotoxin units (EU) and vacuum-dried at 50 degrees C. Average recovery for the Whittaker M.A. Bioproducts Control Standard Endotoxin (CSE), which contained fillers, was 90% (80-100%), for the Difco Laboratories and Associates of Cape Cod endotoxins 47% (40-80% and 20-100%, respectively), and for the rough lipopolysaccharide 70% (40-100%). The presence of fillers appears to increase the percentage of endotoxin recovered and decrease the inconsistency in recovery results. The overall recovery rates for the pure endotoxin formulations were higher and slightly more consistent than those reported in previous studies.
