Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects.

BACKGROUND: Plant sterols have been shown to reduce serum lipid concentrations. The effectiveness is highly dependent on the physical state of the plant sterols. By means of a new crystallizing method, plant sterols can be added into dietary fats and oils homogeneously. In this fat ingredient, plant sterols are in a microcrystalline form. AIMS OF THE STUDY: We investigated the cholesterol-lowering effect and possible side effects of vegetable oil-based spreads fortified with two different doses of microcrystalline plant sterols. METHODS: This double-blind randomized, placebo-controlled study consisted of a 6-wk run-in and a 6-month experimental period. During the run-in period, all 155 hypercholesterolemic subjects received rapeseed oil-based control spread. In the beginning of the experimental period subjects were randomly assigned into one of three experimental groups. The control group continued to use control spread, and the two test groups used spreads with added plant sterols of either 1.5 g/d or 3.0 g/d. The subjects consumed test spreads as a part of their normal diet without any restrictions in lifestyle and diet. RESULTS: Plasma total- and LDL-cholesterol concentrations were significantly reduced by 7.5-11.6% (0.46-0.62 mmol/1) in groups consuming margarine enriched with free plant sterols, compared with the control group. The effects were similar between the two groups consuming either 1.5g or 3.0 g plant sterols per day. No effect on HDL-cholesterol or triacylglycerol concentrations occurred. The test spreads did not induce any adverse effects in blood clinical chemistry, hematology or decreases in serum concentrations of lipid soluble vitamins. CONCLUSIONS: Microcrystalline plant sterols are effective in lowering serum total- and LDL-cholesterol concentrations without obvious side effects. The daily dose of 1.5 g plant sterols is enough to reach the maximum effect.

Visualization of fluid-bed granulation with self-organizing maps.

The degree of the instrumentation of pharmaceutical unit operations has increased. This instrumentation provides information of the state of the process and can be used for both process control and research. However, on-line process data is usually multidimensional, and is difficult to study with traditional trends and scatter plots. The Self-Organizing Map (SOM) is a recognized tool for dimension reduction and process state monitoring. The basics of the SOM and the application to on-line data collected from a fluid-bed granulation process are presented. As a batch process, granulation traversed through a number of process states, which was visualized with SOM as a two-dimensional map. In addition, it is demonstrated how the differences between granulation batches can be studied. The results suggest that SOM together with new in-line process analytical solutions support the in-process control of the pharmaceutical unit operations. Further, a novel research tool for understanding the phenomena during processing is achieved.

Effect of flow rate and type of i.v. container on adsorption of diazepam to i.v. administration systems.

The effect of flow rate and type of i.v. solution container on adsorption of diazepam to i.v. administration systems was studied. Diazepam solutions were prepared in 500 mL of 0.9% sodium chloride injection in glass, polyethylene, and polyvinyl chloride (PVC) containers to a final theoretical concentration of 50 micrograms/mL. PVC administration sets were attached to the containers, and diazepam solution was infused at flow rates of 30, 45, 60, 90, and 120 mL/hr. Solution samples were taken initially and at 0.25, 0.5, 0.75, 1.00, 1.50, 2.00, 3.00, and 4.00 hours after infusion of the first 5 mL of solution through the system. Three infusion trials were performed using each type of container. Adsorption of diazepam to each type of container was evaluated by serial measurements of diazepam concentration over a 168-hour period using five containers of each type. The effect of shaking the container on diazepam adsorption to PVC containers was tested by comparing concentrations in five containers that were shaken during a two-hour period with concentrations in five unshaken containers. Diazepam concentrations were measured spectrophotometrically in duplicate. Diazepam concentrations in glass containers remained unchanged throughout the 168-hour study period; concentrations decreased by about 5% in polyethylene containers and as much as 75% in PVC bags. Shaking increased diazepam adsorption to the PVC container. In the infusion trials, the percentage of diazepam adsorbed increased as flow rate decreased. The amount of diazepam adsorbed to the i.v. administration system was ore dependent on flow rate and infusion time than on the type of container used.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of tubing length on adsorption of diazepam to polyvinyl chloride administration sets.

The effect of administration-set tubing length on adsorption of diazepam to polyvinyl chloride (PVC) tubing was studied, and a simple equation for calculating the dose of diazepam delivered to the patient during an i.v. infusion of diazepam was derived. Diazepam solutions were prepared in 500 mL of 0.9% sodium chloride injection in glass bottles to a final theoretical concentration of 50 micrograms/mL. PVC administration sets were attached to the bottles, and the tubing was then cut to various lengths or the entire length was used for infusion of diazepam solution at a constant rate of 60 mL/hr. Samples of the diazepam solution were collected in glass test tubes initially and after infusion periods of 0.25, 0.5, 0.75, 1.00, 1.50, 2.00, 3.00, and 4.00 hours. Diazepam concentrations were assayed spectrophotometrically in duplicate, and each infusion trial was performed three times. The mean diazepam concentrations in the bottles remained within 100 +/- 1% of initial concentration throughout the study. However, solution samples collected after the four-hour infusion period varied in concentration from 45.5 micrograms/mL using the 23-cm length of tubing to 28.8 micrograms/mL using the entire (185-cm) tubing. Also, the percentage of diazepam adsorbed to the tubing increased as the infusion time decreased. A biexponential equation based on the adsorption data obtained for various tubing lengths was successfully used to calculate the percentage of the theoretical diazepam dose delivered through the tubing during different infusion times. To minimize the adsorption of diazepam to PVC administration sets, the shortest possible length of administration-set tubing should be used.(ABSTRACT TRUNCATED AT 250 WORDS)

Sorptive loss of diazepam and nitroglycerin from solutions to three types of containers.

The sorption of diazepam and of nitroglycerin were studied in glass, polyethylene, and polyvinyl chloride containers with two injectionable solutions. Diazepam and nitroglycerin were diluted to final concentrations of 200 micrograms/ml and 90 micrograms/ml, respectively, in 0.9% sodium chloride or 5% dextrose injection in glass, polyethylene, and polyvinyl chloride containers and stored under room light at 25 +/- 1 degrees C. Samples were taken at 0, 2, 4, 6, and 24 hours after injection of drug. Diazepam was assayed with a spectrophotometer; nitroglycerin was assayed with an automatic chemical analyzer. All solutions were visually compatible. Diazepam and nitroglycerin concentrations remained constant in both i.v. solutions in glass and polyethylene containers. Concentrations of both drugs were reduced in polyvinyl chloride bags to less than 90% of initial within four hours after admixture. No degradation products of either drug were found. It is concluded that sorption of diazepam and nitroglycerin occurs when the drugs are in polyvinyl chloride bags, and that glass and polyethylene containers are superior for these admixtures.