Journal of parenteral science and technology : a publication of the Parenteral Drug Association最新文献

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.

Positively charged membrane filters (Pall, Posidyne) were studied for their ability to retain both bacterial endotoxins and bacteria. Filters (0.2 microns pore size) were challenged with high (up to 5* 10(5) EU) levels of bacterial endotoxin. When the endotoxin was dispersed in water, a more than 10,000 fold reduction of the endotoxin was obtained, whereas the reduction was only a factor 20 when Ringer's solution was used to disperse the endotoxin. Retention of bacteria was dependent on the type of organism, the pore size of the filter and the suspending liquid. Although filters with pore sizes > 0.2 microns were not suitable to be used as a final filter in an aseptic production process, a very reduction in the number of bacteria could be obtained. Possible applications for these filters in the production of sterile pharmaceuticals are discussed.

SVP in glass ampoules are manufactured using two main different technological production processes: the open-ampoule process (O) and the closed-ampoule process (C). In principle, the open-ampoule production technology should lead to better controlled production process. To test this hypothesis and quantify the possible qualitative differences in the manufactured ampoules, a suitable experimental design was set up. The two ampoule production processes have been compared on the basis of the visible particulate burden. Two batches of ampoules filled with water for injections were produced for each type of process, following conventional industrial procedures. Two samples of 20,000 units were taken from each batch and inspected with different automatic inspection systems: two Brevetti CEA machines (S1, S2--light scattering) and two EISAI machines (S3, S4--light absorbtion). The comparison between the processes was based on the rejection percentage. On both inspection machines the open-ampoule production samples present rejection percentages (ranging from 0.154% to 1.248% rejection percentages) which, on average, are lower than those detected in closed-ampoule production (ranging from 1.434% to 3.86% rejection percentages). The difference between the two processes is even more marked if we also consider the data obtained using inspection machines S3 and S4. The substantial differences in performance of the four inspection machines stress the need to provide for adequate validation procedures.

A parenteral admixture composed of 25% of 20% Intralipid, 25% of Azonutril 25, 37.5% of 30% Glucose and 12.5% of 50% Glucose was supplemented with copper, iron and zinc in the organic (gluconate) or inorganic (chloride) form at the following usual final concentrations: copper 0.24 mg/L, iron 0.50 mg/L, zinc 2.00 mg/L. The mixture was stored at 4 degrees C and at 25 degrees C for 24, 48, and 72 hours, and for one week. Determination of the pH indicated good stability of the mixture containing the trace elements in the gluconate form. A significant decrease in the pH of the mixture containing the trace elements as chlorides was noted after one week of storage at both temperatures. Particle size analysis revealed no significant variations between the two formulations after one week of storage. Flocculation kinetics confirmed the results obtained with the other two methods used to determine physicochemical stability. In addition, the kinetics indicated that the possibilities of coalescence processes are highly reduced in all cases. It may be concluded that the two type of mixtures remain stable for Seven days at 4 degrees C and 25 degrees C. However, mixtures containing trace elements in gluconate form should be chosen in cases of longer storage.

Sterility test results gathered over a ten year period have been analysed to determine the effects of the incubation period. Overall there was no difference between the membrane filtration test and direct inoculation in the time required for visible growth of contaminants. Growth occurred earlier if products had no preservative or antimicrobial substances. However use of the membrane filtration method did not significantly enhance the efficiency of detection at seven days incubation. Regardless of the nature of the product or the method of test an unacceptable proportion of contaminants would be missed by limiting incubation to seven days.

Siliconized stoppers, when used with parenteral drug products, have been shown to be a source of particulate contamination. In this study, five different variables: pH of the solution, buffer concentration, Teflon coating on the stopper, autoclaving cycle (F0), and lot-to-lot variation of the siliconization process were evaluated using an eight-run Plackett-Burman design with respect to their impact on the level of particulate contamination from siliconized stoppers. Results show that pH of the solution can significantly affect the particulate level of samples using siliconized stoppers (p < 0.05). An alkaline solution (pH = 8) was shown to produce a higher particulate load than an acid solution (pH = 4). The main effect of the remaining four variables was determined to be statistically insignificant (p > 0.15).

It was clear that there was little consensus among the panel with regard to the need for an informational chapter in USP on microbial classification of cleanrooms. The articulated positions of the individual panelists remained essentially unchanged throughout the session. What agreement was achieved was in a willingness to continue the dialogue, to await the outcome of the PDA activities cited above with the hope that a mutually acceptable compromise can be realized through that process.