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

The chemical stability of the cardioprotective agent ICRF-187 in 0.9% sodium chloride and 5% dextrose infusion fluids has been investigated. The admixtures (concentration: 10 mg/mL and 1 mg/mL) were stored in glass bottles or polyvinyl chloride containers at 4 degrees C in the dark and at room temperature (20-22 degrees C) both protected from light and under normal room fluorescent light conditions in a day-night rhythm. Samples withdrawn immediately after preparation and after 6 hours, 1, 2, 3 and 6 days were analyzed using high performance liquid chromatography with ultraviolet detection. Samples were also inspected for visual changes and tested for changes in pH. Chemical stability of ICRF-187 was also investigated as a function of pH (range 1-12) at room temperature. It is concluded that ICRF-187 is slightly more stable in 5% dextrose than in 0.9% sodium chloride infusion fluids. The stability of the drug is not influenced by normal room fluorescent light nor by the type of container material used. Precipitation occurred in both 5% dextrose and 0.9% sodium chloride with a drug concentration of 10 mg/mL and storage in the refrigerator at 4 degrees C. The chemical stability of ICRF-187 in aqueous solution is mainly a function of pH. At pH 1, no decomposition is detected within 24 hours, at pH 7, 35% decomposition occurs in 21 hours, while at pH 12 it degrades completely within 20.5 hours.

To enhance the physical stability of two model proteins during solution agitation, we investigated the interaction of the nonionic surfactant poloxamer 407 (Pluronic F-127) with each protein. Vigorous agitation of aqueous solutions of interleukin-2 and urease which contained no poloxamer 407 and were maintained at 4 degrees C resulted in a greater than 50% loss in the biological activity at 12 and 24 hours, respectively. Similar aqueous solutions which were maintained at 4 degrees C and contained either urease or interleukin-2 and poloxamer 407 at a concentration of 10% w/w and 0.5% w/w, respectively lost negligible biological activity when left undisturbed for 96 hours. Moreover, when aqueous solutions of urease and interleukin-2 which contained poloxamer 407 at a concentration of 10% w/w and 0.5% w/w, respectively were maintained at 4 degrees C and subjected to agitation for 96 hours, no significant loss in the biological activity was observed for either protein. In addition, urease was observed to have increased enzymatic activity at early time points regardless of the hydrodynamic solution conditions and poloxamer 407 concentrations evaluated. In contrast, a negligible enhancement in the biological activity of interleukin-2 was observed when aqueous solutions of the protein were exposed to similar hydrodynamic conditions employed for urease solutions, but different poloxamer concentrations (0% w/w vs. 0.5% w/w). Results of molar ellipticity, [theta], versus wavelength, lambda, profiles using CD spectropolarimetry on individual aqueous solutions of both proteins containing 2% w/w poloxamer 407 were in close agreement to spectrum obtained with each protein in pH = 7 phosphate buffer (PB).(ABSTRACT TRUNCATED AT 250 WORDS)

An accumulation model for predicting the equilibrium solution concentration of leachables migrating from polymeric containers has been applied to the leaching of several solutes from a blend of a styrene-butadiene-styrene block co-polymer and polypropylene. The model considers three accumulation-limiting mechanisms: total available pool, solute solubility and solute partitioning. Equations relating a solute's solvent-water partition coefficients (Po/w and Ph/w) and its polymer partitioning properties have been developed. With these equations, one can predict leachable accumulation from the container weight, solution volume and the solute's partition coefficients. The maximal accumulation of the leachable in solution will be the lowest value predicted via the three accumulation-limiting mechanisms.

Thermal processing of product in its final container to achieve product safety has been a major process operation of the pharmaceutical and food industries for many years. The original batch type autoclave (retort) is still in prevalent use today. However, high volume continuous and semi-continuous methods are also utilized, primarily in the food industry. Each different terminal sterilization method and load type requires assurance of process adequacy. This paper examines some of the types of moist heat terminal sterilizers in both the pharmaceutical and food industries and compares their features.

Two approaches have been investigated for generating USP sterile, pyrogen-free water for injection (WFI) from potable water in the field. The first approach utilizes reverse osmosis (RO), ion exchange, a solid matrix filter containing activated carbon and zeta adsorbent, a final 0.2 microns pore size sterilizing filter and a device for transferring the WFI to an IV bag; prototype systems based on three different hand-operated RO units weigh 1.5-3.5 kg and are capable of producing WFI at rates of 1-10 L/hr. Parenteral solutions were made by adding WFI to an IV bag containing concentrated Ringer's lactate. The second approach, still in the breadboard stage, is similar but utilizes a larger ion exchange column in place of the RO unit and a multiport distribution head to fill a set of 18 1-L IV bags. This system, considered to be disposable, is capable of generating water of WFI quality at a fill rate of 0.5 L/min from a pressurized source.

The Validation Life Cycle is an implementation mechanism which can assist pharmaceutical (and other types of medical product) manufacturers in the organization and execution of validation activities. A considerable body of work exists which identifies how to validate processes of various type and description. Unfortunately, there is a paucity of information on how to organize these individual validation activities into a cohesive whole. This paper describes a suggested means for achieving an organization's validation goals in a rational and effective fashion. To best understand the advantages of a life cycle for validation, a recap of the history of validation in the U.S. pharmaceutical industry is useful.