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PubMed2003

[Estimation of the intake of food additives--methods applied in the European Union].

Guidelines for estimation of food additives intake were prepared by Codex Committee on Food Additives and Contaminants (CCFAC) in 1989. During the period 1994, 1995 three specific directives have been adopted, each of them including an obligation for Member States to introduce systems to monitor the usage and consumption of food additives and to report their findings to the Commission. Recommendations of Commission's experts which should be taken into account for preparing the monitoring system by Member States are based on decision tree, which systematizes proceeding procedures. Above mentioned decision tree might be a tool for elimination of the food additive which intake does not pose a health hazard. ADI (Acceptable Daily Intake) plays the essential role in the risk assessment of food additives intake. The food additives, which were not eliminated during the decision tree considerations require detailed revision of the conditions of their use. Poland, as a Candidate Country for EU, after the accession will also be obligated to introduce the system to monitor the usage and consumption of food additives and to report relevant report to the Commission.

Decision Trees↗
PubMed1990

[Effect of a differentiated additive KNO3 on the quality of Zuławski cheese. I. Nitrate changes in maturing Zuławski cheese].

18 gyle of cheese in three experimental variants were produced: O variant--control product without additive KNO3; 1 variant--with 0.01% of additive KNO3; 2 variant--with 0.02% of additive KNO3. It was found that raw and pasteurized milk was not an essential source of nitrates. During the summer and autumn cycles of production it was noted respectively: 0.0-0.8 mg NO3-/kg and 0.0-7.4 mg NO3-/kg. Content of NO3- ions in cheese starter approximated their content in raw milk. However, content of nitrates in milk after preparing depended mostly on the quantity of added saltpeter. The cheese made without saltpeter was characterized by low level of nitrates, not exceeding 4.2 mg NO3-/kg, and by vestigial presence nitrites. Whereas the cheese made with additive KNO3 included to 40 mg NO3-/kg for 0.01% of additive KNO3 and to 80 mg NO3-/kg for 0.02% of additive KNO3. It was found that the most intense reduction of nitrates in cheese (to 75%) occurred between the phase of pressing and up to the first two weeks of its ripening. After four weeks' ripening process the level of nitrates in cheese became stabilized independently of the quantity of additive KNO3. After six weeks' ripening process, that is when the cheese is sent into consumption, the level of nitrates and nitrites was quite low and did not exceed 3.0 mg NO3-/kg and 1.2 mg NO2-/kg. Manufactured cheese met the requirements of FIL/IDF while taken into consideration the content of nitrates and nitrites.

Cheese↗
PubMed1993

Food additives and allergy.

There is ample evidence that food additives of several sorts may precipitate adverse reactions. Some of these have catastrophic potential such as sulfite sensitivity in asthmatic patients. Fortunately, asthmatic responses to a variety of additives are certainly not as prevalent as once feared, and are probably unusual. Restricted diets are of no general benefit in asthmatic patients. In contrast to asthma, urticarial or other cutaneous reactions to food additives are more common. A restricted diet for a few months' duration may be beneficial, although the mechanism through which this is achieved is unclear. Suspected food additive sensitivities are best documented by oral challenges, preferably in a double-blind manner. Challenges in asthmatic patients need to be done with patients continuing on their routine medications to avoid false positives. All care should be taken to titrate the doses and schedule the doses appropriately, since several of these agents could provoke large drops in pulmonary function. With urticarial patients, an adequate baseline of urticarial activity needs to be established before the challenges so that fluctuations in normal activity are not construed as a positive result. Despite a large number of studies evaluating the role of food additives in hyperkinesis, results are not uniform. Evidence does suggest that there is a small subset of primarily younger children in whom additives will impact on behavior. As with asthma and additives, the problem appears to be much smaller than originally postulated.

Food Additives↗
PubMed2000

A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder.

BACKGROUND: To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone. METHODS: Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition. RESULTS: For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated. CONCLUSION: These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy.

Adult↗
PubMed2006

Enantio- and diastereoselective Michael addition reactions of unmodified aldehydes and ketones with nitroolefins catalyzed by a pyrrolidine sulfonamide.

Chiral (S)-pyrrolidine trifluoromethanesulfonamide has been shown to serve as an effective catalyst for direct Michael addition reactions of aldehydes and ketones with nitroolefins. A wide range of aldehydes and ketones as Michael donors and nitroolefins as acceptors participate in the process, which proceeds with high levels of enantioselectivity (up to 99 % ee) and diastereoselectivity (up to 50:1 d.r.). The methodology has been employed successfully in an efficient synthesis of the potent H(3) agonist Sch 50917. In addition, a practical three-step procedure for the preparation of (S)-pyrrolidine trifluoromethanesulfonamide has been developed. The high levels of stereochemical control attending Michael addition reactions catalyzed by this pyrrolidine sulfonamide, have been investigated by using ab initio and density functional methods. Transition state structures for the rate-limiting C--C bond-forming step, corresponding to re- and si-face addition to the reactive conformation of the key enamine intermediates have been calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis and that the energy barrier for si-face attack in reactions of aldehydes to form 2R,3S products is lower than that for the re-face attack leading to 2S,3R products. In contrast, the energy barrier for re-face addition is lower than that for si-face addition in reactions of ketones. The computational results, which are in good agreement with the experimental observations, are discussed in the context of the stereochemical course of these Michael addition reactions.

Journal Article↗
PubMed1983

Effect of inorganic additives on solutions of nonionic surfactants V: Emulsion stability.

Electrolytes often break emulsions to which they were added as active ingredients, adjuvants, or impurities. The stability of oil-in-water emulsions containing octoxynol 9 NF as the emulsifier and various added electrolytes was investigated by measuring droplet size, turbidity, and oil separation on storage at various temperatures and in a centrifugal field at 25 degrees. Electrolytes were added to hexadecane emulsions after emulsification (direct addition); alternatively, hexadecane was emulsified in octoxynol 9-electrolyte mixtures (reverse addition). Xylene emulsions were prepared by direct addition only. Hexadecane emulsions containing 0.10% octoxynol 9 were considerably more stable than xylene emulsions containing 0.60% because the surfactant is practically insoluble in hexadecane, but miscible in all proportions with xylene. An emulsifier soluble in the disperse phase as well as the continuous phase evidently forms less stable interfacial films. The electrolytes investigated were sulfuric and hydrochloric acids, magnesium nitrate, and aluminum nitrate, which salt octoxynol 9 in by complexation between its ether groups and their cations; sodium thiocyanate, which salts the surfactant in by destructuring water; and sodium chloride and sodium sulfate, which salt octoxynol 9 out. The addition of these electrolytes at concentrations up to 2 or 3 m to hexadecane emulsions produced fast and extensive creaming, little or no flocculation, no coalescence, and only minor changes in droplet size or turbidity on storage at room temperature. The extent of coalescence during centrifugation was actually reduced by the additives. Such stability is unusual. Droplet size and turbidity depended mainly on octoxynol 9 concentration. The greatest decrease in the former and increase in the latter occurred when the concentration was increased from 0.10 to approximately 0.4%. All emulsions became slightly coarser on storage at 25 degrees. Stability at 50 degrees was impaired by aluminum nitrate and magnesium nitrate and to a lesser extent by sodium sulfate and sodium chloride. Reverse-addition emulsions differentiated better between the electrolytes than direct-addition emulsions. Electrolytes salting octoxynol 9 in, especially by complexation, generally produced the finest and most stable emulsions. Similarly, xylene emulsions were destabilized more by the electrolytes which salted the emulsifier out than by those salting it in. Centrifugation of hexadecane emulsions at 7800 X g compressed the creamed emulsion layer into a plug of clear, transparent, isotropic gel from which coalesced hexadecane separated slowly on further centrifugation.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena↗
PubMed2006

Direct comparison between genomic constitution and flavonoid contents in Allium multiple alien addition lines reveals chromosomal locations of genes related to biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of shallot (Allium cepa L.).

The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot monosomic addition lines (FF+nA). This study deals with the production and biochemical characterisation of A. fistulosum-shallot multiple alien addition lines carrying at least 5A to determine the chromosomal locations of genes for quercetin formation. The multiple alien additions were selected from the crossing between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113 plants obtained from this cross were analysed by a chromosome 5A-specific PGI isozyme marker of shallot. Thirty plants were preliminarily selected for an alien addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to 23. The other extrachromosomes in 19 plants were completely identified by using seven other chromosome markers of shallot. High-performance liquid chromatography analyses of the 19 multiple additions were conducted to identify the flavonoid compounds produced in the scaly leaves. Direct comparisons between the chromosomal constitution and the flavonoid contents of the multiple alien additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis of quercetin from kaempferol was located on 7A and that an anonymous gene involved in the glucosidation of quercetin was on 3A or 4A. As a result of supplemental SCAR analyses by using genomic DNAs from two complete sets of A. fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol synthase to 4A.

Allium↗
PubMed2003

Control of Lactobacillus contaminants in continuous fuel ethanol fermentations by constant or pulsed addition of penicillin G.

The addition of penicillin G to combat microbial contamination in continuous fuel alcohol fermentations was performed using both continuous and pulsed addition regimes. In continuous fermentations where both Saccharomyces cerevisiae and Lactobacillus paracasei were present, the mode of addition of penicillin G determined final numbers of viable L. paracasei. When the same overall average concentration of penicillin G was added in both pulsed and continuous modes, the initial viable number of L. paracasei (8.0 x 10(9) cfu ml(-1)) decreased to a greater degree (1.02 x 10(5) cfu ml(-1) L. paracasei) when penicillin G was pulsed at 6 h frequencies at an overall average concentration of 2,475 U/l than when penicillin G was added continuously at 2,475 U/l (2.77 x 10(5) cfu ml(-1) L. paracasei). Pulsed additions over longer frequencies at 2,475 U/l were not as effective in reducing viable bacteria. Viable yeasts increased during both treatment conditions by more than 2-fold. The two addition regimes also eliminated the 40% decrease in ethanol concentration caused by the intentional bacterial infection. Although there was 3 times more bacterial death with 6 h pulsed additions compared to continuous additions of penicillin G at 2,475 U/l, there was, by that point, no practical difference in either final ethanol concentration or relative ethanol recovery.

Anti-Bacterial Agents↗
PubMed2005

Widespread evidence for non-additive genetic variation in Cloninger's and Eysenck's personality dimensions using a twin plus sibling design.

Studies using the classical twin design often conclude that most genetic variation underlying personality is additive in nature. However, studies analyzing only twins are very limited in their ability to detect non-additive genetic variation and are unable to detect sources of variation unique to twins, which can mask non-additive genetic variation. The current study assessed 9672 MZ and DZ twin individuals and 3241 of their siblings to investigate the environmental and genetic architecture underlying eight dimensions of personality: four from Eysenck's Personality Questionnaire and four from Cloninger's Temperament and Character Inventory. Broad-sense heritability estimates from best-fitting models were two to three times greater than the narrow-sense heritability estimates for Harm Avoidance, Novelty Seeking, Reward Dependence, Persistence, Extraversion, and Neuroticism. This genetic non-additivity could be due to dominance, additive-by-additive epistasis, or to additive genetic effects combined with higher-order epistasis. Environmental effects unique to twins were detected for both Lie and Psychoticism but accounted for little overall variation. Our results illustrate the increased sensitivity afforded by extending the classical twin design to include siblings, and may provide clues to the evolutionary origins of genetic variation underlying personality.

Australia↗
PubMed1990

Addition of a hypoxic cell selective cytotoxic agent (mitomycin C or porfiromycin) to Fluosol-DA/carbogen/radiation.

In an effort to develop effective combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen (95% O2/5% CO2) breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiation, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cytotoxicity of radiation (10 Gy) more in the bright cell subpopulation (4-fold) than in the dim cell subpopulation (2-fold) resulting in an overall 4-fold sparing of the dim subpopulation. Mitomycin C and porfiromycin were both more toxic toward the dim cell subpopulations. Addition of mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation (10 Gy) resulted in a primarily additive effect of the drugs and radiation killing in both tumor cell subpopulations. Thus, with mitomycin C/Fluosol-DA/carbogen and radiation there was a 2-fold sparing of dim cells and with porfiromycin in the combined treatment a 1.6-fold sparing of the dim cell population. Our results indicate that treatment strategies directed against both oxic and hypoxic tumor subpopulations can markedly increase the tumor cell kill achieved by radiation.

Animals↗
PubMed1995

The safety and regulatory status of food, drug and cosmetics colour additives exempt from certification.

Colour additives exempt from certification (also known as 'natural colour additives') are commonly used in the United States to colour foods, drugs and cosmetics. The US Food and Drug Administration established regulations governing the use of these colour additives, and the labelling of the products that contain them. The safety of these colour additives has been demonstrated by safety testing programs that have yielded a significant amount of toxicology data, and also by a long and well documented history of safe use in the United States and elsewhere. In this report we review the data supporting the safety of the colour additives that are exempt from certification and approved for use in the USA, and conclude that the safety of these colour additives is well supported by the available data. Relevant aspects of the regulation of these colour additives are also described.

Cosmetics↗
PubMed2003

Susceptibility of the hydroxyl groups in serine and threonine to beta-elimination/Michael addition under commonly used moderately high-temperature conditions.

The beta-elimination/Michael addition reaction has been employed for the modification of O-acylated and phosphorylated Ser and Thr residues in a variety of derivatives. The modified Ser and Thr can be analyzed by amino acid composition analysis, N-terminal Edman degradation sequence analysis, and tandem mass spectrometric sequencing which generally allows the identification and localization of the phosphorylation or glycosylation sites. However, the reactivity of the free hydroxyl group on serine and threonine by sodium hydroxide-induced beta-elimination has not been critically examined. In this study, two analogous phosphopeptides, KMpSTLSYR and KMSpTLSYR, were subjected to beta-elimination under the widely used conditions previously reported, followed by sulfite or ethanethiol addition. After treatment of the phosphopeptides in 0.1 N NaOH/0.6 M Na(2)SO(3) at 37 degrees C for 24 h, matrix-assisted laser desorption ionization-time of flight mass spectrometric analyses of the products revealed an appreciable mass peak with an additional observed mass of 64 compared to the expected mass from the conversion of phosphate to sulfite. Similarly, treatment of the phosphopeptides in 0.52 N NaOH/1.36 M ethanethiol at 50 degrees C for 18 h or for even as short as 1h also yielded additional 44 mass of ethylthiogroup in excess of the expected mass for the modified phosphopeptide. Electrospray ionization tandem mass spectrometric analysis confirms that the modification occurred on the hydroxyl group of Ser and Thr in addition to P-Ser and P-Thr. On the other hand, modification on the free hydroxyl group of Ser or Thr was not detected under the mild condition of 0.1 N NaOH/0.6 M Na(2)SO(3) at 25 degrees C for 24 h as previously reported. This finding suggests that temperatures above 25 degrees C and excessive alkalinity should be avoided to prevent the beta-elimination of the hydroxyl group of Ser and Thr in peptides. This is of particular concern when employing highly sensitive tandem mass spectrometric methods for the identification and localization of Ser and Thr as modification sites by the beta-elimination/Michael addition reaction. The additional modification site(s) may complicate the interpretation of data and lead to an erroneous conclusion.

Hydroxyl Radical↗
PubMed2004

CaO--P2O5--Na2O-based sintering additives for hydroxyapatite (HAp) ceramics.

We have assessed the effect of CaO--P2O5--Na2O-based sintering additives on mechanical and biological properties of hydroxyapatite (HAp) ceramics. Five different compositions of sintering additives were selected and prepared by mixing of CaO, P2O5, and Na2CO3 powders. 2.5 wt% of each additive was combined with commercial HAp powder, separately, followed by ball milling, and sintering at 1250 degrees C and 1300 degrees C in a muffle furnace. Green and sintered densities of the compacts were analyzed for the influence of additives on densification of HAp. Phase analyses were carried out using an X-ray diffractometer. Vickers microhardness testing was used to evaluate hardness of sintered compacts of different compositions. A maximum microhardness of 4.6 (+/- 0.28) GPa was attained for a composition with 2.5 wt% addition of CaO:P2O5:Na2O in the ratio of 3:3:4. Results from mechanical property evaluation showed that some of these sintering additives improved failure strength of HAp under compressive loading. Maximum compressive strength was observed for samples with 2.5 wt% addition of CaO. Average failure strength for this set of samples was calculated to be 220 (+/- 50) MPa. Cytotoxicity, and cell attachment studies were carried out using a modified human osteoblast cell line called OPC-1. In vitro results showed that these compositions were non-toxic. Some sintering aids enhanced cell attachment and proliferation, which was revealed from SEM examination of the scaffolds seeded with OPC-1 cells.

Bone Substitutes↗
PubMed2006

Recovery of dynamic balance after additional small divided doses of midazolam given intravenously for sedation.

We have previously reported that a dynamic balance test with perturbation stimuli and computerised dynamic posturography sensitively reflected the inhibitory effect on balance of intravenous midazolam sedation given intravenously as a single dose, and recovery time was within 80 min. The purpose of this study was to investigate the recovery of dynamic balance after additional doses of midazolam. Eighteen young adult male volunteers were sedated with midazolam given intravenously. The initial dose was given until the Wilson sedation score reached 3, and an additional dose was given until the same score was obtained 40 min later. They were tested with perturbation stimuli 40, 80, 100, and 120 min after the additional doses had been given. Their recovery time was recorded. The mean (S.D.) initial dose of midazolam was 0.07 (0.005) mg kg(-1), and additional doses were 41 (7)% of the initial dose. The serial changes in bispectral index after initial and additional doses were similar. The recovery time for the dynamic balance test (within 80 min) was the same as that recorded in the previous single-dose study. The recovery time of the psychomotor function test was within 75 min. Additional doses of midazolam aiming for a Wilson sedation score of 3 at a dose about 40% of the initial dose and given 40 min after the initial dose are valid in terms of the maintenance of sedation and recovery of dynamic balance. Complete recovery time, including psychomotor function, was within 80 min of the additional dose of the drug.

Adult↗
PubMed2006

Influence of additives on the properties of Bis-GMA/Bis-GMA analog comonomers and corresponding copolymers.

OBJECTIVES: The purpose of this study was to evaluate the effect of two additives: propionaldehyde (aldehyde) and 2,3-butanedione (diketone) on the properties of Bis-GMA diluted with TEGDMA and the synthesized Bis-GMA analogs, propoxylated Bis-GMA (CH(3)Bis-GMA) and propoxylated fluorinated Bis-GMA (CF(3)Bis-GMA). METHODS: Nine experimental comonomers were prepared combining Bis-GMA and TEGDMA, CH(3)Bis-GMA, CF(3)Bis-GMA, with aldehyde (32mol%) and diketone (32mol%). Photopolymerization was effected by using Camphorquinone (0.2wt%) and N,N-dimethyl-p-toluidine (0.2wt%). Experimental comonomer viscosity (Brookfield viscometer), polymerization shrinkage (gravimetrically), degree of conversion (FT-IR) and contact angles (contact angle goniometer) were determined. Comonomer and copolymer T(g)s (DSC and Fox equation) were also evaluated. Data were analyzed by one-way ANOVA and Tukey test (alpha=0.05). RESULTS: Bis-GMA/CH(3)Bis-GMA and Bis-GMA/CF(3)Bis-GMA with additives exhibited lower viscosities (p<0.01). Inclusion of additives into the comonomer systems did not produce significant increase in polymerization shrinkage (p>0.05). A significant increase in degree of conversion was shown for Bis-GMA/TEGDMA and Bis-GMA/CH(3)Bis-GMA with additives (p<0.01). Additives reduced contact angle and comonomer T(g) values, whereas the corresponding copolymers with additives showed an increase in T(g). SIGNIFICANCE: Use of novel comonomer systems with the addition of aldehyde and diketone functional groups would improve dental resin composite properties.

Aldehydes↗
PubMed2004

Limitations of additive EuroSCORE for measuring risk stratified mortality in combined coronary and valve surgery.

OBJECTIVE: To study the use of the additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) to predict mortality following adult combined coronary artery bypass grafting (CABG) and valve surgery. METHODS: Data were collected prospectively, from all four centres providing adult cardiac surgery in the north west of England, on 1769 consecutive patients undergoing combined CABG and valve surgery between April 1997 and March 2002. Observed in-hospital mortality was compared to predicted mortality as determined by both additive and logistic EuroSCORE. RESULTS: Observed mortality for simultaneous CABG and valve surgery was 8.7%, compared to 6.7% (additive) and 9.4% (logistic). Sixty-five percent of patients were classified as high-risk (additive EuroSCORE >5); the observed mortality was 11.5%, compared to 8.1% (additive) and 12.8% (logistic). Discrimination was similar in both systems as measured by the C statistic (additive 0.73, logistic 0.73). CONCLUSIONS: The logistic EuroSCORE is more accurate at predicting mortality in simultaneous CABG and valve surgery, as the additive EuroSCORE significantly under-predicts in this high-risk group.

Adult↗
PubMed2005

Percolation phenomenon in mixed reverse micelles: the effect of additives.

The conductivity of AOT/IPM/water reverse micellar systems as a function of temperature, has been found to be non-percolating at three different concentrations (100, 175 and 250 mM), while the addition of nonionic surfactants [polyoxyethylene(10) cetyl ether (Brij-56) and polyoxyethylene(20) cetyl ether (Brij-58)] to these systems exhibits temperature-induced percolation in conductance in non-percolating AOT/isopropyl myristate (IPM)/water system at constant compositions (i.e., at fixed total surfactant concentration, omega and X(nonionic)). The influence of total surfactant concentration (micellar concentration) on the temperature-induced percolation behaviors of these systems has been investigated. The effect of Brij-58 is more pronounced than that of Brij-56 in inducing percolation. The threshold percolation temperature, Tp has been determined for these systems in presence of additives of different molecular structures, physical parameters and/or interfacial properties. The additives have shown both assisting and resisting effects on the percolation threshold. The additives, bile salt (sodium cholate), urea, formamide, cholesteryl acetate, cholesteryl benzoate, toluene, a triblock copolymer [(EO)13(PO)30(EO)13, Pluronic, PL64], polybutadiene, sucrose esters (sucrose dodecanoates, L-1695 and sucrose monostearate S-1670), formamide distinctively fall in the former category, whereas sodium chloride, cholesteryl palmitate, crown ether, ethylene glycol constitute the latter for both systems. Sucrose dodecanoates (L-595) had almost marginal effect on the process. The observed behavior of these additives on the percolation phenomenon has been explained in terms of critical packing parameter and/or other factors, which influence the texture of the interface and solution properties of the mixed reverse micellar systems. The activation energy, Ep for the percolation process has been evaluated. Ep values for the AOT/Brij-56 systems have been found to be lower than those of AOT/Brij-58 systems. The concentration of additives influence the parameters Tp and Ep for both systems. A preliminary report for the first time on the percolation phenomenon in mixed reverse micelles in presence of additives has been suggested on the basis of these parameters (Tp and Ep).

Journal Article↗
PubMed2005

Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel--effect of additives.

Injectable polymeric formulation for paclitaxel was studied. Poly ricinoleic acid and sebacic acid were synthesized. The effect of additives on the viscosity of polymer, paclitaxel release, and polymer degradation was investigated both in vitro and in vivo. Additives that were used in this study were ricinoleic acid, phospholipid, PEG 400, and PEG 2000. Addition of 20% ricinoleic acid to P(SA:RA)3:7 liquefied the formulation and allowed injection of the formulation containing paclitaxel via a 22-G needle at room temperature with no effect on paclitaxel release rate. Addition of PEG 400, PEG 2000, and phospholipid to the formulation did not affect the paclitaxel release from the formulation. The degradation of modified formulations with paclitaxel and additives was examined in vitro and by subcutaneous injection of liquid formulations to the backspace via a 22-G needle into seven groups of four C3H mice. In vivo formulations with additives (20% ricinoleic acid and PEG or phospholipid) and 5% paclitaxel content degraded faster than the formulation with only 20% ricinoleic acid and the same paclitaxel content: 51% and 54% versus 43%. The slowest degradation (26% in 1 week) was of the formulation containing 10% paclitaxel. The release rate in vivo was affected by the paclitaxel content; the higher the content, the slower was the release. By using additives, we could adjust the physical characteristics of the surgical paste while maintaining a desirable system for sustained paclitaxel release.

Animals↗