Kinetic stability of all-in-one parenteral nutrition admixtures in the presence of high dose Ca2+ additive under clinical application circumstances.

BACKGROUND: TPN infusions are usually administered during a treatment period of 10-24 hours per day due to the metabolic capacity of the liver. During this time interval physicochemically stable TPN solution (emulsion) is needed for the treatment. The purpose of the present study was to examine how the kinetic stability features of ready-made total parenteral nutrition admixtures containing olive oil and soybean oil will change under the usage-modeling 24-hour application with and without overdose Ca2+. METHODS: Particle size analysis and zeta potential measurements were carried out to evaluate the possible changes in the kinetic stability of the emulsions. RESULTS: Our results indicate that in two of the four mixtures bimodal droplet-size distribution figures were detected and appearance of fat particles over 5 µm can not be disclosed. The tendency for separation of large diameter droplets in the two types of oil-based emulsion systems was different. In case of soybean containing emulsion second peak of droplets appeared in the bottom of the container in contrast to the olive oil containing emulsions where the second peak appeared in the surface layer. Interestingly this phenomenon is independent of calcium-content. CONCLUSIONS: From therapeutic point the emulsions of the bigger droplets containing upper layer are safer because the potentially dangerous big droplets could remain in the infusion bag after the administration.

[Colloid-physical characterization of supramolecular drug delivery systems]. / Szupramolekuláris gyógyszerhordozó rendszerek kolloidfizikai jellemzése.

Cyclodextrins are well-known biocompatible oligosaccharides capable of forming inclusion complexes with suitable guest molecules. They can be expediently used as solubilizers for hydrophobic pharmacon molecules in aqueous solutions. In this study, the effect of colloidal and non-colloidal additives on the solubility of statins is described. Two statin-derivatives (lovastatin and simvastatin), beta-cyclodextrin (-CD) and randomly methylated beta-cyclodextrin (RAMEB) were used as complexing agents. Those pharmacons are widely used in the management of cardiovascular diseases involving high or elevated blood cholesterol levels. Complexation of the highly lipophilic statin molecules with beta-CD and RAMEB was studied in the presence and the absence of dissolved polyvinyl-pyrrolidone (PVP). For the characterization of the stability of statin-CD complexes, association constant of binary associates have been calculated. It was found that inclusion complexation can beneficially enhance the solubility of both statin-derivatives. In binary statin-CD solutions predominantly associates of 1:1 molar ratio form, which show significant surface activity. In polymer-containing ternary systems, the solubility of the pharmacons can further be increased. This phenomenon can presumably be explained with the formation of statin-CD-polymer ternary associates of supramolecular structure. In such supramolecular assemblies the amphiphilic statin-CD complexes are likely bound to the macromolecules' chains. The wetting properties of solid, dried and powdered complexes were studied by immersion enthalpy measurements. Both in binary and ternary systems a significant increase in the immersion enthalpy values could be detected, which indicates that the complexes exhibit fairly hydrophilic character.

Tracking of the kinetic stability of 2 types of total nutrient admixtures containing different lipid emulsions.

The physical stability of 2 types of total nutrient admixtures was studied as a function of storage time and temperature. One of them contained only structured triglycerides and the other exclusively long-chain triglycerides as lipid components. To evaluate the possible changes in the kinetic stability of the emulsions and in the surface characteristics of the droplets during storage, particle size analysis, zeta potential, and dynamic surface tension measurements were performed. To follow any chemical decomposition processes that occurred during storage, the pH of the emulsions was also monitored. The mean droplet size of emulsions prepared with lipids containing exclusively long-chain triglycerides showed a remarkable increase after 4 days of storage, in contrast with that of the mixtures containing structured lipids. A combination of size distribution, zeta potential, and dynamic surface tension measurements proved to be useful for an adequate tracking of the kinetic stability of total nutrient admixtures. Structured triglycerides not only provide advantageous metabolic effects but improve the physical stability of total parenteral nutrition admixtures.

The effect of structured triglycerides on the kinetic stability of total nutrient admixtures.

PURPOSE: The physical stability of two types of total parenteral nutrient (TPN) admixtures was studied as a function of storage time and temperature. One of them contained only structured triglycerides and the other exclusively long-chain triglycerides as lipid components. METHODS: Droplet size of the mixtures was followed by photon correlation spectroscopy for 10 days. Zeta potential and dynamic surface tension measurements were carried out to evaluate the possible changes in the charge and interfacial surface tension of the emulsion droplets during the storage. pH values were monitored in order to follow the possible decomposition processes in the course of storage. RESULTS: Droplet size of emulsions prepared with lipids containing exclusively long-chain triglycerides showed remarkable increase after 4 days of storage in contrast with that of the mixtures containing structured lipids. CONCLUSIONS: The obtained results indicate that besides the advantageous metabolic effects of structured triglycerides, their application is recommended to improve the physical stability of TPN admixtures.

[Interactions in solution between cyclodextrins and statins]. / Ciklodextrinek es sztatinok kölcsönhatásának in vitro vizsgálatai.

Cyclodextrins (CDs) are cyclic oligosaccharides, capable of forming inclusion complexes with hydrophobic molecules in aqueous solution and therefore, of improving the bioavailability of many drugs. They are biocompatible with living cells and do not cause toxic side effects. In this study, interactions in aqueous solutions between chemically different CDs and lovastatin and simvastatin, respectively, were investigated. It was found that the solubility of both statins can be considerably increased by the CD derivatives. The influence of the chemical structure of CD and of the temperature and pH on the solubility of the statin derivatives is described. Possible ways of increasing the solubility of these cholesterol-lowering drugs and their utilization in practice are also outlined.

[Kinetic study of the liquid uptake of retraction cords]. / Retrakciós fonalak folyadékfelvevó képességének kinetikai vizsgálata.

The soaking time ensured for the liquid uptake of retraction cords is a crucial factor in the successful gingival retraction procedure. The aim of the present investigations was to determine the optimal soaking time for three cords of different thickness. The capability of liquid uptake of the cords was measured by a gravimetric method using four different sulcus retraction solutions. In addition to the time of soaking, the saturation of the cords with the solutions largely depended on the wetting properties and the pore structure of the cords as well. Our results indicate that 20 minutes soaking time is necessary for saturation before using in the clinical application of the cords. This conclusion applies for conditions when air bubbles are manually removed before soaking.

Enhancement of drug solubility in supramolecular and colloidal systems.

Statins, as efficient HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme-A) reductase inhibitors are widely used in the management of cardiovascular diseases. Interactions in aqueous solutions between highly lipophilic statins and cyclodextrins (CDs) in the absence and the presence of a dissolved polymer or its monomeric compound, respectively, were studied. The solubility of lovastatin and simvastatin at various temperatures and pHs were investigated by phase-solubility measurements. Surface activity of solutes in binary (CD-statin) and ternary (CD-statin-polymer) systems was studied by determining the surface tension of the solutions. For the characterization of the CD-statin inclusion complexes, stability constants for associates of different molar ratios have been calculated. It was shown that complexation may lead to improvement of the aqueous solubilities of both statins by 1-2 orders of magnitude. Especially, randomly methylated beta-cyclodextrin (RAMEB) showed outstanding solubilizing effects. In binary systems dominantly CD-statin associates of 1:1 molar ratios form, which exhibit considerable surface activity. RAMEB forms more stable complexes with these drugs than the native beta-CD, and also the surface activity of the former solutes is higher. In polymer-containing ternary systems the solubility of both statins could be further improved. The enhanced drug solubilities can be ascribed to the formation of CD-statin-polymer associates with supramolecular structure. A portion of the surface active CD-statin complexes are very likely anchored at the macromolecular chains. In these solutions, the total amounts of solutes are composed of the sum of the "free" binary and the supramolecular ternary associates.

Influence of the chain composition on the thermodynamic properties of binary and ternary polymer solutions.

Thermodynamic properties of binary and ternary polymer solutions (one or two uncharged polymers in one solvent) were studied. Poly(vinyl pyrrolidone) (PVP), fully hydrolyzed poly(vinyl alcohol) (PVA) homopolymers, and water-soluble poly(vinyl alcohol-co-vinyl acetal, -vinyl propional, and -vinyl butiral) copolymers with various acetal content and chain structure, respectively, were used in the experiments. The hydrophilic/hydrophobic character of the PVA-based macromolecules and their compatibility with the PVP homopolymer were systematically regulated by changing the chemical structure of the copolymers (acetal content and/or length of side chains). The water activities in binary and ternary solutions of the chemically different polymers were determined by a gel-deswelling method developed here for ternary solutions. On the basis of the Flory-Huggins theory, the relevant solvent-segment and segment-segment pair interaction parameters (chi) have been calculated. The chi12 segment-solvent interaction parameters proved to be sensitive indicators for changes in the chemical structure of the copolymers. With increase of either the acetal content or the length of side chains in the copolymer, chi12 approached the value characteristic of a theta condition. No significant differences could be revealed in the segment-segment interaction parameters obtained for the PVP-copolymer mixtures with various acetal derivatives, when the chi12 and chi13 interaction parameters determined in binary solutions were used in the calculations for chi23. Determination of the parameters chi1,23 as suggested by Panayiotou, however, showed that increasing the acetal content or the length of the hydrophobic side chains in the copolymer resulted in a reduction in the interaction between the PVA "acetals" and PVP molecules.

In vitro kinetic study of absorbency of retraction cords.

STATEMENT OF PROBLEM: The soaking time required for liquid uptake by retraction cords is a crucial factor in the successful gingival retraction procedure. PURPOSE: The aim of this investigation was to determine the optimal soaking time for 3 retraction cords of different thickness to ensure adequate uptake of the hemostatic solution. MATERIAL AND METHODS: Braided ULTRAPAC retraction cords of 3 different thicknesses (No. 00, No. 0, and No. 1) with identical lengths (35 mm) were used. The capability of the cords to absorb liquids was measured by a gravimetric method. Different sulcus retraction solutions (epinephrine, aluminum chloride, and ferric sulfate) were tested, with physiological saline solution used as the control. The cords were soaked for various time intervals (2 seconds; 1, 5, and 60 minutes; and 24 hours) in the medicament solutions at room temperature. Immediately before immersion, air inclusions that may have inhibited the inner moistening of the cords were manually pressed out. In each of the 4 treatment groups, 75 pieces of cord were tested by determining the grams of fluid absorbed by grams of dry cord (gram/gram). Before the cord was weighed, excess fluid accumulating on the outer surface of the cord was removed by filter paper saturated in the corresponding test solution. The data were analyzed by F test analysis, and P<.05 was regarded as significant. RESULTS: In each group, regardless of the cord type (No. 00, No. 0, or No. 1) or medicament solutions tested, the amount of fluid absorbed increased with the soaking time, but to different extents. A logarithmic relationship in a linear plot between the amount of fluid absorbed and the soaking time was demonstrated. The relationship established offered an exact determination of both the rate and the saturation level of liquid uptake. The rate of liquid uptake calculated from the saturation equations exhibited significant correlation with the cord thickness (P<.05). The saturation levels of the solutions did not show correlation with the cord thickness (P>.30). CONCLUSION: Within the limitations of this study, the results indicated that 20 minutes of soaking time was necessary for saturation of the cords before use, provided that air trapped within the cords was removed. In addition to the soaking time, the saturation of the cords with the solutions largely depended on the wetting of the cords.