Effects of nonionic surfactants on the physical stability of immunoglobulin G in aqueous solution during mechanical agitation.

The objective of this study was to evaluate the influence of nonionic surfactants in the presence of glycine and sodium chloride on the physical stability of immunoglobulin G (IgG) in aqueous solution. Among surfactants suitable for parenteral preparation, Polysorbate 80 (Tween 80) and Polyoxyl 35 Castor Oil (Cremophor EL) were selected. The physical stability of IgG in the absence and in the presence of excipients was investigated in aqueous solution during mechanical agitation (concentration of IgG 15%; pH 7.1; temperature 6 +/- 2 degrees C). Suitable concentrations of Tween 80 and Cremophor EL were experimentally determined by surface tension measurements at 6 +/- 2 degrees C. Glycine and sodium chloride were used in different concentrations. The influence of the excipients on the physical stability of IgG in solution has been examined by surface tension measurements, protein content assay (Kjeldahl and HPLC) and differential scanning calorimetry (DSC). Based on the results of the investigations, it was found that Tween 80 and Cremophor EL, used in experimentally determined critical micelle concentration (cmc), decreased the physical stability of IgG in solution. Tween 80 and Cremophor EL in the presence of glycine (1.5 g/l) could stabilize the IgG in solution during mechanical agitation. The comparison of the effects of Tween 80 and Cremophor EL on the physical stability of IgG, showed that Tween 80 had better stabilization effects on IgG in solution under the experimental conditions selected.

An investigation into interactions between polyacrylic polymers and a non-ionic surfactant: an emulsion preformulation study.

The aim of this study was to investigate possible interactions between a polymeric emulsifier and a non-ionic surfactant, with a view of achieving better understanding of emulsion stabilisation mechanisms. The polymeric emulsifier used was acrylates/C10-30 alkyl acrylate crosspolymer (Pemulen TR-2(R)), while Polyoxyethylene 20 sorbitan mono-oleate (Polysorbate 80) has been chosen as a model surfactant. Both materials were used within the concentration range relevant for their practical application. A 0.2%w/w aqueous dispersion of polymeric emulsifier, containing various amounts of surfactant (from 0.01 to 1.0% w/w) was used throughout the study. Interfacial aspects of the proposed polymer/surfactant interactions were analysed by means of surface tension measurements. Changes in the network structure of the test dispersions were quantified by continuous shear rheometry, supported by the texture analysis. To analyse the influence of hydrophobic alkyl groups present on the Pemulen TR-2(R) chains, an unmodified, hydrophilic polyacrylic acid polymer, Carbopol 934P(R), was assessed under the same conditions. The results obtained by both surface tension and rheological studies have revealed large differences in behaviour of the two polymers in the presence of the model surfactant. Pemulen TR-2(R) was shown to desorb the surfactant from the surface, within the whole concentration range studied. Furthermore, an increase in viscosity and texture profile parameters with increasing Polysorbate 80 concentration up to 0.3% w/w was evident in the case of Pemulen TR-2(R) dispersions. This was followed by a decrease in the gel network strength at higher surfactant concentrations. On the other hand, Carbopol 934P(R) has shown no signs of surfactant desorption and only small changes in the network structure with the increasing concentration of surfactant. It is shown in this study that an interaction between a polymeric emulsifier Pemulen TR-2(R) and a non-ionic surfactant Polysorbate 80 does occur in their aqueous dispersion, and that it is: (a) hydrophobic in nature; (b) concentration-dependent; and (c) has an impact on the rheological properties of dispersion.

Serum beta-endorphin level in patients with depression on fluvoxamine.

The main interest of the present study was to determine possible alternations in beta-endorphin serum levels in healthy volunteers and in patients with depression, as well as changes in beta-endorphin serum levels caused by fluvoxamine treatment. Fluvoxamine maleate (Fevarin) was administered orally at a dose of 200 mg/day for 4 weeks. The serum levels of beta-endorphin were lower in patients with 'nonendogenous' depression (104.68 +/- 5.29 pg/ml) and those with 'endogenous' depression (36.34 +/- 2.23 pg/ml) than in healthy volunteers (125.19 +/- 1.64 pg/ml). The endogenously depressed patients had significantly lower beta-endorphin levels than the nonendogenous patients. A 4-week treatment of fluvoxamine (200 mg/day) caused a statistically significant increase in beta-endorphin serum levels in all patients (nonendogenous depression 132.10 +/- 2.38 pg/ml and endogenous depression 50.09 +/- 2.45 pg/ml) in comparison to values found before the onset of the therapy. The efficacy of fluvoxamine was 11.0 (+/- 9.0) evaluated by the Hamilton Rating Scale for Depression (HAMD) in the patients with a diagnosis of depression. These results indicate that determination of beta-endorphin serum levels could be a valuable laboratory test in the diagnosis of depression.

The Influence of Processing Variables on Performance of O/W Emulsion Gels Based on Polymeric Emulsifier (Pemulen (R)TR-2NF).

Pemulens(R) (BF Goodrich) are hydrophobically-modified copolymers of acrylic acid (Acrylates/C10-C30 alkyl acrylates) that could act both as primary emulsifiers for o/w emulsions and viscosity enhancing agents. The aim of this study was to assess the influence of different processing conditions (mixing equipment, speed and time of agitation) on the aesthetic characteristics, viscosity and physical stability of o/w emulsion gels based on the polymeric emulsifier (Pemulen TR-2 NF). This objective was achieved by applying a two-factor three-level experimental design at two sets: using a laboratory mixer and a disperser. Independent variables were mixing speed and time and dependant variables i.e. responses, were millimetres of oil phase separated after centrifugation at 3500 rpm in a laboratory centrifuge, and viscosity at shear rate 180 l/s. The responses were fitted into a second order model by means of a multiple regression analysis. For the samples prepared on the laboratory mixer it was shown that mixing time and speed produce a statistically important influence on viscosity, but not on physical stability: with increasing mixing speed and time the viscosity linearly increases. If we assume that greater energy input obtained by increasing the mixing speed and time produces a decrease in drop size and polydispersity and better developed gel network, then the optimal processing conditions will be at the point where maximal viscosity is attained. This result was in accordance with the centrifugation test - the best stability appeared when maximal mixing speed and time were applied, although this effect appeared not to be statistically significant. For samples prepared using dispersers no statistically important influence of processing variables on viscosity and physical stability was found. Additionally, emulsion samples prepared using the laboratory mixer appeared homogenous, while in samples prepared using the disperser, undispersed polymer lumps appeared. Based on physical characteristics of the emulsions, it could be concluded that the disperser is an inappropriate tool for processing the emulsions based on Pemulen polymers.

[Extrapyramidal side effects of 2 different formulations of fluphenazine chloride injections]. / Ekstrapiramidalni sporedni efekti dviju razlicitih formulacija flufenazin-hlorid injekcija.

Comparison of extrapyramidal side effects of two fluphenazine hydrochloride injections. Lyogen and Moditen was carried out by the in vivo experiments in mice. The incidence, intensity and duration of the catalepsy in mice after i. m. application of 10 mg/kg fluphenazine hydrochloride in two forms of sterile water solution have been observed. Catalepsy of significant intensity occurred after a short period of 15 minutes regarding the both formulations and maximal values were observed 30 and 60 minutes after application of Lyogen, and Moditen respectively. Significant values of cataleptic intensity with respect to control group (the water for injection-treated group) were registered during 28 hours after the application of both formulations. This study of cataleptic effects could not confirm significant differences between these two formulations, between the rate of occurrence and duration of effects. On the other hand, the difference between intensities were observed and were more prominent in the period between 6-24 hours. An the most cases they were not significant (p greater than 0.05).