Journal of pharmaceutical science and technology : the official journal of PDA最新文献

The amount and pyrogenicity of challenged endotoxin (derived from E. coli 055:B5, 10,000 endotoxin units, EU) processed in a dry heat oven at 200 degrees and 250 degrees C was measured and compared with the predicted amount and pyrogenicity calculated from destruction kinetics. The values for the assayed amount and pyrogenicity of the endotoxin processed in the dry heat oven at 200 degrees and 250 degrees C were fairly close to the predicted values. When the challenged endotoxin was exposed for 60 min in a dry heat oven at 200 degrees C, the amount of destruction did not reach a 3 log cycle reduction, although the pyrogenicity of the endotoxin was sufficiently reduced. However, at 250 degrees C for 30 min in the dry heat oven, the amount of endotoxin destroyed quickly reached a 3 log cycle reduction, and the pyrogenicity was quickly reduced to a sufficient level.

An instrumental method to analyze protein solutions for visual appearance is described which is based on spectrophotometric comparison to reference suspensions with varying degrees of turbidity. This method provides a useful substitute for visual inspection of uniform opalescent suspensions in that it is more convenient and less time-consuming and has the potential to be more reproducible, accurate and objective. Established categories of opalescence based on European Pharmacopoeial reference suspensions were determined using turbidity measured as optical density in the 340-360 nm range. A comparison of the mean optical density of a protein sample to those of the reference suspensions allowed a more reproducible assignment of the sample's category of opalescence than that of visual inspection.

Microbiological control in clean piping systems is limited by transport processes that distribute the disinfecting medium. The critical locations where transport resistance can be expected are the piping dead legs. Transport in dead legs was analyzed theoretically for two common disinfection methods: thermal; and ozone treatment. Established guidelines for clean piping design should not be universally applied. Specific guidelines for these different technologies are proposed. By differentiating between permanent and temporary dead legs, ozonated systems can be designed to be at least as reliable as thermal systems. Scale-up of thermal systems should include increasing the circulating velocity of the loop.

Parenteral or dietary lipids have been shown to alter the acyl composition of tissue lipids effectively. It has been suggested that the changes in the acyl composition would modulate physiological responses by altering the kinetic properties and/or activity of the cellular enzymes. One such enzyme is protein kinase C whose activity is regulated by receptor-mediated phospholipid hydrolysis. In this study, we have examined the effect of cis-unsaturated fatty acid on the activity of protein kinase C and protein phosphorylation in the hippocampus. Our results suggest that cis-fatty acid indeed modulates protein phosphorylation in the hippocampus and the cis-fatty acid-induced protein phosphorylation can be attributed to the activation of protein kinase C.

Reduction in subvisible particle counts in parenteral formulations is an important requirement. Despite selection of best container/closure and use of processing conditions where the drug is most soluble and stable, lyophilized formulations often demonstrate problems of subvisible particle counts greater than the permitted compendial limits. We have studied some formulation and processing approaches with different compounds with the intention of developing lyophilized products, which after reconstitution, pass compendial subvisible particle limits for large volume parenterals (LVP). The approaches studied were targeted to reduce "intrinsic" subvisible particle counts and included the addition of a solubilizing agent, pH adjustment, charcoal treatment of the process solution, and use of a filter with finer pore size for filtering the solution prior to lyophilization. Although the relative efficiency of each of these parameters in reducing subvisible particle counts was found to be slightly different for each compound, the inclusion of a solubilizing agent and charcoal treatment of the processing solution were found to have the most pronounced effect. The combination of two or more parameters was often found to be even more effective. It is suggested that these approaches may be useful in developing other lyophilized products that yield low subvisible particle counts on reconstitution.

AG-331, a water-soluble glucuronate salt of a potential anticancer drug, was synthesized using a technology described as "Protein Structure-based Drug Design." A lyophilized product containing 44.4% (w/w) of AG-331, 55.6% (w/w) of mannitol and trace of water was developed for parenteral delivery of AG-331. The pre-lyophilized solution, which contains 2.0% (w/v) of AG-331 and 2.5% (w/v) mannitol can be aseptically filtered through commonly used 0.2-micron filters without significant AG-331 loss. The filter of choice was made of PTFE (polytetrafluoroethylene) membrane. The lyophilized product is stable under accelerated conditions for at least 6 months. The product can be sterilized with gamma-irradiation. The AG-331 reconstituted solution in 5% Dextrose Injection, USP is stable in PVC infusion bags for at least 2 days at 5 degrees C and 30 degrees C.