Solid-state fluorescence of the trihydrate phases of ampicillin and amoxicillin

The purpose of this work was to study the effects of crystal structure on the solid-state photoluminescence of the trihydrate phases of ampicillin and amoxicillin, and to contrast these spectra with analogous spectra obtained on the molecules dissolved in a solution phase. The polymorphic identity of the analytes was established using x-ray powder diffraction and Fourier transform infrared absorption spectroscopy, and the solid-state luminescence spectra obtained under ambient conditions. It was found that the solid-state excitation and emission spectra of ampicillin trihydrate and amoxicillin trihydrate were dominated by energy transfer and exciton effects, which were manifested as decreases in the energy of the excitation and emission bands of the solid-state systems relative to those of the free molecule in solution. The photoluminescence data revealed that in spite of the known structural similarity of ampicillin trihydrate and amoxicillin trihydrate, the magnitude of the Davydov splitting, and the degree of band energy shifting differed between the 2 systems. This finding indicates that the small differences in crystal structure existing between the 2 compounds leads to measurable differences in the patterns of energy transfer. Published: October 22, 2005     

Transformation of lactulose trihydrate into anhydrous lactulose by fluidized bed drying and its characterization

Stable anhydrous lactulose was produced from lactulose trihydrate by stepwise heating on a fluidized bed. The processes were performed on stable powder forms. The anhydrous lactulose was characterized by an opaque white appearance, a coarse surface structure with random cracks and indentations, a high degree of crystallization, stability under humid conditions, and by X-ray powder diffraction, differential thermal analysis, and differential thermogravimetry. Those characteristics were different from those of the original trihydrate, which was transparent, had a smooth surface and a higher degree of crystallization, was stable under humid conditions and had different X-ray powder diffraction, differential thermal analysis, and thermogravimetric characteristics. The transformation was enhanced when the inlet temperature was 45-55 degrees C or when the temperature of the fluidized bed was over 40 degrees C. At these cutoff temperatures, both crystalline forms were observed.     

Comparative bioavailability of three brands of ampicillin

The relative biological availability (bioavailability) of three brands of ampicillin trihydrate capsules marketed in Canada was studied by means of a crossover experimental design and was evaluated by analysis of variance. After administration of a single oral dose (500 mg.) to volunteer subjects, the mean peak ampicillin serum concentration and the area under the time ampicillin serum concentration curve (AUC) were higher for one of the products than for the other two. A second study utilizing the same experimental design revealed no differences in these parameters when different production lots of the more available product were compared. Product bioavailability was not related to the in vitro dissolution time of the capsules. The experimental design and methods of statistical analysis are discussed.     

Vapor-Induced Phase Transformations in Docetaxel

Vapor-induced transformations of docetaxel anhydrous (form D(A)) under ambient conditions have been studied using methanol, ethanol, and water as the solvent media. The online vapor-induced transformations were monitored by powder X-ray diffractometry. New solid forms (solvates/hydrates/anhydrous) of docetaxel anhydrous were obtained in stoichiometric ratios which were characterized completely using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis, and spectroscopic ((13)C solid-state nuclear magnetic spectroscopy, solution (1)H NMR, and Fourier transform infrared) techniques. The new forms namely methanol solvate (D(M)), ethanol solvate (D(E)), monohydrate (D(MH)), trihydrate (D(TH)), and anhydrous (D(AN-I) and D(AN-II)) were identified through structural analysis.     

Toxicological characteristics of ampicillin]

Toxocity of ampicillin trihydrate was studied in acute and chronic experiments. It was shown that the antibiotic had low acute toxicity, did not cumulate and had no skin-irritating effect. On its inhalation in concentrations of 5 mg/m3 for 4 months, ampicillin induced allergization of albino rats, decreased their immunity. The general toxic effect of the drug was slightly pronounced. Ampicillin in a concentration of 0.1 mg/m3 induced tension of the immunological reactivity of the organism. The maximum permissible concentration (MPC) of ampicillin in the working premises equal to 0.1 mg/m3 is recommended. Mark "Allergen" is necessary.     

Drug-polymer microparticles produced by supercritical assisted atomization

The supercritical assisted atomization (SAA) was proposed as a new technique to produce composite microparticles for drug controlled release. Ampicillin trihydrate and chitosan were selected as model drug and carrier, respectively, and 1% v/v acetic acid aqueous solution was used as solvent. The effect of the polymer/drug ratio on particle morphology and drug release rate was evaluated. SEM analysis indicated that non-coalescing spherical microparticles formed by chitosan/ampicillin were produced by SAA. All coprecipitates produced have a sharp particle distribution, with diameters ranging between about 0.1 and 6 microm. SAA composite microparticles were characterized by X-ray, DSC, EDX and UV-vis analysis. A solid solution of the chitosan and ampicillin was produced and a stabilizing effect of the polymer on the drug has resulted that protects ampicillin from thermal degradation. A prolonged release from SAA coprecipitates with respect to raw drug and physical mixtures of chitosan and ampicillin was obtained; moreover, the polymer/drug ratio has revealed to be a controlling parameter for drug release. Drug release mechanisms characteristic of swelling-controlled systems were observed, with ampicillin release depending on both relaxation and diffusive mechanisms. An empirical binomial equation was used to describe experimental data, showing a fair good agreement with ampicillin release data if both the relaxational and the diffusional parameters are function of the polymer/drug ratio.     

坛紫菜叶状体的无菌化培养及其应用

对坛紫菜叶状体的无菌处理方法进行了优化,并利用紫菜外生菌对无菌处理后的紫菜叶片进行了人工感染。经0.7%KI和0.1%(w/v)氨苄青霉素对紫菜叶片进行预处理后,利用氨苄青霉素、硫酸链霉素、新霉素、庆大霉素及卡那霉素等5种抗生素及其不同组合对紫菜叶片进行处理,筛选出最佳抗生素组合、浓度和培养条件。结果表明:氨苄青霉素(终浓度300μg/mL)、卡那霉素(终浓度100μg/mL)与庆大霉素(终浓度100μg/mL)3种抗生素组合对坛紫菜叶状体进行无菌处理18 h,对紫菜细胞的毒害较小,并且3种抗生素合用对89.5%紫菜外生细菌的抑菌率达80%以上;外生菌感染结果研究表明:用105/mL真菌孢子液和细菌菌液回染紫菜,培养22 d后,实验组紫菜生长状况较对照组好,对照组紫菜出现褪色。用108/mL真菌孢子液分别回染健康紫菜、穿刺紫菜(用灭菌刀片在紫菜表面划1～2 mm的伤口),分别在18℃、28℃和35℃条件下培养。实验结果表明28℃和35℃高温和穿刺均会影响无菌紫菜健康生长,且加菌紫菜在高温和穿刺条件下,则会出现明显病斑,而18℃培养的加菌紫菜则生长良好。     

An examination of the moisture sorption characteristics of commercial magnesium stearate

The objective of this study was to characterize the moisture sorption of magnesium stearate and the morphological changes, if any, resulting from moisture sorption. Six samples of commercial magnesium stearate USP were examined. Moisture sorption isotherms were obtained at 25°C and 5% to 98% relative humidity (RH) using a moisture balance. Changes in crystal form resulting from moisture sorption were determined by x-ray diffraction. There were differences in the shape of the isotherm, reversibility of moisture uptake, and shape of the hysteresis loop in the isotherms of crystalline and amorphous magnesium stearates. The isotherm of crystalline magnesium stearate was almost parallel to the pressure axis until and RH of ∼80%. The isotherm of the amorphous sample was characterized by continuous uptake of water over the entire range of RH. Exposure of amorphous magnesium stearate to RH greater than 70% resulted in the formation of the trihydrate. The trihydrate was converted into the anhydrous form when heated to a temperature of 100°C to 105°C. The trihydrate could be generated by exposing the anhydrate to RH higher than 70%.     

Influence of peroxidation products of liposomal lipids on antibacterial activity of liposomes]

The dynamics of accumulation of lipid peroxidation products (LPPs) in suspensions of phosphatidyl choline-cholesterol liposomes at various acidity levels was studied. It was shown that intensity of the accumulation of LPPs was inversely proportional to the suspension pH. When the liposomes were incubated together with the cells of Pseudomonas aeruginosa, there was a decrease in the level of LPPs in comparison to that in the suspension which did not contain bacterial cells. The accumulation of LPPs in the incubation medium correlated with the bacteria death rate in the suspension. There was a direct relationship of the antibacterial activity of the liposomal suspension on its content of LPPs.     

Feasibility of Focused Beam Reflectance Measurement (FBRM) for Analysis of Pharmaceutical Suspensions in Preclinical Development

This study examined the use of focused beam reflectance measurement (FBRM) for qualitative and quantitative analysis of pharmaceutical suspensions with particular application to toxicology supply preparations for use in preclinical studies. Aqueous suspensions of ibuprofen were used as prototype formulations. Initial experiments were conducted to examine the effects of operational conditions including FBRM probe angle, probe location, and mixing (method and rate of mixing) on the FBRM analysis. Once experimental conditions were optimized, the homogeneity and sedimentation-redispersion of particles in the suspensions were assessed. Ibuprofen suspension under continuous agitation was monitored using FBRM for 60 h to study particle size change over time. Another study was performed to determine if particle count rates obtained by FBRM could be correlated to suspension concentration. The location and the angle of the FBRM probe relative to the beaker contents, and the rate and the method of mixing the suspension were found to be sensitive parameters during FBRM analysis. FBRM was able to monitor the process of particle sedimentation in the suspension. The attrition of ibuprofen particles was detectable by FBRM during prolonged stirring with an increase in the number of smaller particles and decrease in the number of larger particles. A strong correlation was observed between particle count rate by FBRM and ibuprofen concentration in the suspension. Also, change in content uniformity in the suspension at different locations of the beaker was represented by FBRM particle count. Overall, FBRM has potential to be a useful tool for qualitative and quantitative analysis of pharmaceutical suspensions.     

Effects of antibiotics on fitness of the B biotype and a non-B biotype of the whitefly Bemisia tabaci

The whitefly, Bemisia tabaci Gennadius (Homoptera: Aleyrodidae), harbors primary and secondary endosymbionts. Previous research showed that the invasive B biotype and an indigenous non‐B biotype (named non‐B ZHJ‐1 population) of B. tabaci from Zhejiang, China, harbored different endosymbionts. To investigate the function of these endosymbionts in the two biotypes of B. tabaci, we fed adult whiteflies with three antibiotics, tetracycline, ampicillin trihydrate, and rifampicin, and evaluated the fitness of their offspring on cotton plants. These three antibiotics did not remove the primary endosymbiont Portiera aleyrodidarum but were capable of eliminating the secondary endosymbionts. In the B biotype, treatments of adults with tetracycline or ampicillin trihydrate accelerated development and increased the survival of their offspring, while treatment of adults with rifampicin significantly retarded the development of their offspring but did not affect their survival. In the non‐B ZHJ‐1 population, treatments of adults with tetracycline or ampicillin trihydrate also accelerated the development of their offspring but did not significantly affect their survival, while treatment of adults with rifampicin significantly retarded development and reduced the survival of their offspring. These results suggest that removal of some secondary endosymbionts and/or reduction of the primary endosymbiont from B. tabaci may produce both favorable and unfavorable effects on the fitness of the host insects.     

Measurements of viscosity of synthetic erythrocyte suspensions

Measurements were made of the viscosity of suspensions of synthetic erythrocytes composed of hemoglobin solutions encapsulated in liposomes, as a function of shear rate, temperature, suspension concentration, lipid membrane composition, and the viscosity of the suspending medium. It was found that the viscous behavior of the synthetic erythrocyte suspensions was non-Newtonian and nearly the same as that of suspensions of natural erythrocytes prepared similarly, with the major difference being that synthetic erythrocyte suspensions are somewhat more viscous. Suspensions of Fluosol FC-43 prepared similarly were found to be essentially Newtonian fluids, and substantially different and more viscous than either erythrocyte suspension. The higher viscosity of synthetic erythrocyte suspensions probably accounts for the ability of these suspensions to maintain normal systemic vascular resistance in transfusion experiments, in spite of the fact that synthetic erythrocytes are smaller than natural erythrocytes.     

Effect of high osmotic media on blood viscosity and red blood cell deformability

Effects of high osmotic media on the shape and deformability of RBC were examined for determining increasing factors of blood viscosity. Dog blood and Urographin (a hypertonic contrast medium) were used; the plasma osmolality was changed by Urografin suspended in blood. The viscosity was measured for normal RBC and glutaraldehyde-treated RBC suspensions with a cell volume concentration. The RBC deformability was evaluated from the difference in viscosity between the two suspensions. It was shown that normal RBC suspension increased the viscosity with increase in osmolality at high shear rate; hardened RBC suspension decreased the viscosity with increase in osmolality. It was concluded that the RBC deformability decreased with increasing osmolality.     

Extraction from Plant Tissue and Germination of Oospores of Peronospora viciae f.sp. pisi

A protocol was developed to extract oospores of Peronospora viciae f.sp. pisi from plant tissue and control bacterial contamination in a germination assay. Oospores were extracted by comminuting infected leaves and pods in water, sonicating the suspension and sieving it through mesh sizes 53 and 20 pm, respectively. Germination of oospores was negatively influenced by addition of chloramphenicol and penicillin. A combination of ampicillin and rifampicin strongly inhibited bacterial growth at 10 C, and did not negatively affect germination. Washing oospores in water or 0.02% Tween-80, and sonication did not influence germination. Treating oospore suspensions with cellulase buffered at pH 4.6 for 2 h digested most plant tissue but did not influence germination. Incubation in 0.05 m acetate buffer delayed germination. Germination was unaffected when oospores were incubated in 0.05 m citrate buffer.     

Shear Flow Behavior of Aqueous Suspensions of Potato Parenchyma Powder

The shear flow behavior of potato powder suspensions prepared from two different particle sizes and with a range of solids volume fraction (Φ) was studied. A concentrated sucrose solution was used as the continuous phase to maintain particle buoyancy. The shear flow properties were measured at 20, 50 and 80 °C. The suspensions obeyed a power-law equation in the dilute regime while the Herschel-Bulkley equation was the best fit for almost all semi-dilute and more concentrated suspensions. With increasing Φ, particle size and temperature, a gradual development of shear-thinning behavior was evident which coincided with an increase in the consistency index and the development of a yield stress in the suspensions. Potato powder suspensions therefore behave very differently to potato starch suspensions, with flow properties dominated by the effect of intra- and inter-cellular components in the potato powder particles that are transferred to the continuous phase and that alter suspension properties.     

Flocculation properties of pectin in various suspensions

Pectin had a flocculating activity and its flocculating activities in various suspensions were investigated. Flocculating activity of pectin in a kaolin suspension was markedly stimulated by the addition of Al3+ and Fe3+ to the suspension. Optimum temperature for flocculating activity of pectin in the kaolin suspension was around 30 degrees C and high flocculating activity was obtained when 30 mg/l of pectin and 0.2 mM Fe3+ were added to the suspension. Other inorganic suspensions of activated carbon and acid clay were flocculated by pectin in the presence of Al3+ or Fe3+. Flocculation of organic suspensions such as cellulose and yeast by pectin occurred when 0.1-0.2 mM Fe3+ was present in the suspensions.     

Properties of intracellular ribonuclease utilized for RNA reduction in disintegrated cells of Saccharomyces cerevisiae.

The properties of intracellular RNase in disintegrated cell suspensions of Saccharomyces cerevisiae have been studied. The influence of salt addition and/or incubation of the suspension on the activity of RNase and on the degradation of endogenous RNA was determined. No significant change in the RNase activity in the disintegrated suspensions was obtained by addition of 3% NaCl or by incubation at 50 degrees C with 3% NaCl. During the incubation with NaCl the active RNase was able to degrade endogenous RNA. By incubation without salt the RNase was inactivated. Inactivation also occurred after extraction at alkaline pH. The RNase had an optima at pH 5-6 and temperatures between 50-60 degrees C. The main part of the RNase in the unincubated suspension was soluble also at pH 4.0. No serious protein degradation occurred during the short time incubation needed for RNA reduction. 70% of the protein in the suspensions was recovered in the precipitate at pH 4.0 after 20 min of incubation. The corresponding protein recovery from unincubated suspensions was 77%.     

A device for aeration and mixing of cell and organelle suspensions during nuclear magnetic resonance studies

A device is described which maintains homogeneous aerobic or anaerobic cell and organelle suspensions within an NMR sample tube. Line broadening due to magnetic field inhomogeneity is reduced by elimination of gas bubbles from the area of the probe receiver coils. The linewidth of the extracellular orthophosphate resonance of a yeast suspension in 31P NMR was 0.21 ppm compared with 0.4-0.7 ppm in conventionally aerated suspensions. Recirculation of the sample results in complete mixing within 90 s of addition of aliquots of acid or alkali. The maximum rate of oxygen transfer from the gaseous to the liquid phase was approximately 600 microM min-1 when aerated with 95% oxygen/5% carbon dioxide. A 60% wet weight suspension of yeast cells was recirculated for 20 h without settling of cells occurring. A method for estimating oxygen transfer rate is described.     

Turbulent flow of red cells in dilute suspensions. Effect on kinetics of O2 uptake.

The turbulent flow properties of dilute (0.06% by volume) suspensions of human red blood cells in 4-mm-bore glass tubing were estimated by laser anemometry. The flow properties of the dilute red cell suspension were similar to those of a dilute suspension of polystyrene spheres (0.5 micron diameter) in isotonic NaCl solution. Flow was found to be laminar when the Reynolds number was below 2,000, transitional in the range of Reynolds numbers from 2,000 to 3,000, and fully turbulent above Reynolds number 3,000. These results differ from previous studies of more concentrated red cell suspensions. The length scales of the turbulence were also estimated: at a Reynolds number near 4,000 the macroscale is about 1.25 mm, the Taylor microscale is about 0.85 mm, and the Kolmogoroff scale is near 0.075 mm. The results are discussed in relation to previous measurements of the rate of oxygen uptake by dilute red cell suspensions in the flow-type rapid reaction apparatus. Our results suggest that under the conditions of most of these oxygen uptake measurements, the turbulent flow is characterized by eddies about 1 mm across, mixing with each other on a time scale of about 45 ms. Since most of the reported oxygen uptake measurements involve a similar time scale, it is possible that an effective "unstirred layer" influenced the reported rate of oxygen uptake.     

Inhibition of anthracycline semiquinone formation by ICRF-187 (Dexrazoxane) in cells

The formation of semiquinone free radicals of doxorubicin, epirubicin, daunorubicin, and idarubicin was measured by electron paramagnetic resonance (EPR) spectroscopy in hypoxic suspensions of chinese hamster ovary (CHO) cells. The amount of semiquinone produced was in the order idarubicin > doxorubicin > daunorubicin > epirubicin. The idarubicin semiquinone signal was both the fastest to be formed and to decay. Idarubicin, which was the most lipophilic of the anthracyclines studied, also displayed the fastest fluorescence-measured cellular uptake of drug. Thus, it was concluded that semiquinone formation was dependent upon the rate of cellular uptake. Lysed cell suspensions were also shown to be capable of producing the doxorubicin semiquinone in the presence of added NADPH. The cardioprotective agent dexrazoxane (ICRF-187) was observed to decrease the amount of doxorubicin semiquinone observed in cell suspensions. Dexrazoxane also decreased the amount of doxorubicin semiquinone observed in the NADPH-lysed cell suspension mixture. Neither bipyridine nor deferoxamine decreased NADPH-dependent doxorubicin semiquinone formation. These results suggest that dexrazoxane does not decrease doxorubicin semiquinone formation through an iron complex formed from hydrolyzed dexrazoxane. Dexrazoxane may be inhibiting an NADPH-dependent enzyme.