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

It is important to remember that: 1. WHO is an international organization representing 182 member countries. 2. WHO has a constitutional mandate inter alia to "develop, establish and promote international standards with respect to biological, pharmaceutical and similar products." 3. Its present programme covers such activities as WHO Good Manufacturing Practices, the International Pharmacopoeia, International Nonproprietary Names (INN), WHO Certification Scheme, the Model List of Essential Drugs and many other subjects concerning safety, efficacy and quality. 4. Emphasis is now directed to the feasibility of further harmonization of requirements for drug registration and quality control having regard to the number of countries with increasing manufacturing facilities.

Poloxamer (Pluronic) nonionic surfactant vehicles are a series of chemically-related block copolymers finding widespread use in parenteral formulations as solubilizing and wetting agents for traditional, low-molecular weight organic drug molecules, as well as stabilizing agents for proteins and polypeptide drugs. We report the effects of poloxamer 407 (Pluronic F-127) on plasma cholesterol and triglyceride concentrations in rats. Poloxamer 407 injected into rats by intraperitoneal injection (dose = 1.5 gm/kg) resulted in sustained (greater than 96 hour) hypercholesterolemia and hypertriglyceridemia. A larger dose of poloxamer 407 was required to elevate plasma triglyceride relative to total cholesterol. Ingestion of commercial rat chow had a negligible effect on plasma cholesterol and triglycerides levels in control (no poloxamer injection) animals, but consumption of food by animals that received an intraperitoneal injection of poloxamer 407 (30% w/w) resulted in significantly (p < .05) greater elevations in plasma cholesterol and triglycerides than in fasted animals administered poloxamer 407. The route of poloxamer 407 administration, namely intramuscular vs. intraperitoneal injection, was observed to be a more important factor for poloxamer-induced elevations in plasma cholesterol than poloxamer-mediated elevations in plasma triglycerides. Our results also provide suggestive evidence that the mechanism responsible for the elevation of plasma cholesterol following intraperitoneal injection of a poloxamer 407 solution (30% w/w) to rats may be due to stimulation of 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase activity in the liver by the poloxamer vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminium (Al ) is abundant in our environment and is a contaminant of electrolyte solutions used in the manufacture of Total Parenteral Nutrition (TPN) solutions administered to neonates, who are unable to tolerate oral feeding. Previous studies by McHalsky et al. (1) have shown concern over the levels of aluminium in parenteral products, and there are special considerations needed with regard to neonatal TPN solutions, (2). It is felt that neurotoxicology and abnormalities of bone histology may be seen with aluminium deposition in the tissues. In the present study it was shown that the average aluminium contamination in TPN solutions was in the order of 205 micrograms/L. It is well documented that aluminium is chelated successfully in dialysis solutions by desferrioxamine (DFO), Allain et al. (3). Using an AA spectrophotometer equipped with a graphite furnace, the average amount of aluminium in compounded neonatal TPN solutions was determined. Equimolar amounts of DFO to aluminium were added to various neonatal TPN formulations, and the physical stability of each solution was determined using microscopic and electronic particle counting analysis. This study suggests that aluminium can be irreversibly chelated with DFO and stable TPN solutions can be prepared.

A Parenteral Drug Association (PDA) Committee on Software Validation was formed about three years ago to address some of the issues associated with validating automated systems, particularly where all, or part, of the automated system is supplied by outside vendors. A Technical Report that describes a process which emphasizes system definition, a comprehensive system specification, system qualification and ongoing evaluation will issue later this year. The concepts described in this document will be consistent with the PMA's System Development Life Cycle approach which is commonly used for computer system validation. The following article has been developed from the System Definition section of this PDA Technical Report.

Problems inherent in traditional methods of determining the hemolytic activity of parenteral compounds are discussed. Data taken from a study which closely models the conditions present for an intravenous injection are re-examined. An equation is given which combines several variables into a single parameter, the effective concentration. A strong relationship is found between the effective concentration of the compound of interest and the hemolysis produced.

A novel method of determination of protein stability is described, which involves interfacial shear rheology of adsorbed protein layers. This technique provides information on the structural-mechanical properties of the adsorbed protein layers which can be related to: the rate of interfacial adsorption, interfacial interactions, and conformational changes in the adsorbed layers. The interfacial shear rheology of the blood proteins, bovine serum albumin and human immunoglobulin G was investigated. The air/aqueous and oil/aqueous interfaces were studied and the interfacial rheological activity of BSA was shown to be similar at three hydrophobic interfaces: air, squalene and mineral oil. The kinetics of interfacial film formation was shown to be time dependent, and aging effects were detected in both interfacial and bulk molecules. The absolute interfacial elasticity values decreased as the temperature increased. The protein solutions exhibited no interfacial rheological activity in the presence of the small surfactant molecules, Tween 80 and lecithin, under the conditions studied.

Epifluorescence microscopy of the microcolonies obtained after filtration of a deliberately contaminated intravenous solution, was used for the rapid detection and enumeration of the bacteria. The technique is adequate for the test of low volume solution (with low contamination). Also it allows one to detect a single colony forming unit (c.f.u.)/mL, with great correlation between fluorescence counts and pour plate colony counts; the morphology of microcolonies is typical for most of the microorganisms and it allows a primoidentification (for a trained analyst).

Biodegradable microspheres were evaluated as vaccine adjuvants based on their ability to provide prolonged release of incorporated agents. Hepatitis B surface antigen (HBSA) prepared by recombinant DNA technology was chosen as a model antigen and encapsulated into polyglycolic acid (PGA) by solvent extraction and solvent evaporation techniques. Five microsphere formulations were prepared to evaluate effect of microsphere size and the presence of immunostimulants such as muramyl dipeptide (MDP) or aluminum hydroxide. The microspheres were characterized for size distribution, surface morphology and antigenicity. Guinea pigs were chosen as the animal model for evaluation of antigenicity of the formulations. The animals were divided into seven groups of four animals each and the microsphere formulations were injected intraperitoneally, using alum adsorbed HBSA as positive control and placebo microspheres as negative control. Blood samples were withdrawn from the animals by toe clipping at two, four, six and sixteen weeks and plasma was analyzed for antibodies against hepatitis B by an enzyme linked immunoassay. At sixteen weeks, the animals were reinjected and evaluated for antibody response at two, four and six weeks post second injection. Antibody response to the microspheres was higher than control. Smaller size microspheres elicited earlier antibody response while the larger size microspheres provided delayed and longer duration of antibody production. Microspheres with MDP potentiated the antibody response. The results demonstrate the applicability of biodegradable microspheres for immunization against hepatitis B.