Characterization of starch, agar and maltodextrin blends for controlled dissolution of edible films.

Biopolymer blend interactions influence the physical, mechanical and barrier properties of edible packaging. Starch (rice and hydroxypropyl cassava starch mixture), agar and maltodextrin were formulated to control the solubility of edible films. Blend materials were characterized for fluid rheology, solid microstructure, mechanical barrier and physical properties. Agar enhanced solid behavior and governed low temperature gelation of the blends, giving improved film forming ability and hydrophobicity. Flexibility of the films highly depended on integrity of polymer networks. Agar formed continuous networks entangled in starch matrices. Conversely, maltodextrin acted as a filler that reduced mechanical strength at high concentration (>40%) due to interruption of network integrity. Interaction between starch and agar led to poor water solubility that was insignificantly impacted by agar concentration (10% to 30%) due to identical molecular bonding. Maltodextrin produced highly miscible and plasticized starch-agar films and led to reduced mechanical relaxation temperature and shriveling of film structures after mold dipping. Solubility increased linearly with higher maltodextrin concentration. Molecular interaction between maltodextrin and starch/agar matrices insignificantly influenced solubility, while strong interaction between starch and agar highly controlled solubility. Findings clarified the interaction mechanisms and behavior of biological macromolecule materials in fluids and solid matrices for manufacture of edible packaging.

Nanoparticle heterogeneity: an emerging structural parameter influencing particle fate in biological media?

Drug nanocarriers' surface chemistry is often presumed to be uniform. For instance, the polymer surface coverage and distribution of ligands on nanoparticles are described with averaged values obtained from quantification techniques based on particle populations. However, these averaged values may conceal heterogeneities at different levels, either because of the presence of particle sub-populations or because of surface inhomogeneities, such as patchy surfaces on individual particles. The characterization and quantification of chemical surface heterogeneities are tedious tasks, which are rather limited by the currently available instruments and research protocols. However, heterogeneities may contribute to some non-linear effects observed during the nanoformulation optimization process, cause problems related to nanocarrier production scale-up and correlate with unexpected biological outcomes. On the other hand, heterogeneities, while usually unintended and detrimental to nanocarrier performance, may, in some cases, be sought as adjustable properties that provide NPs with unique functionality. In this review, results and processes related to this issue are compiled, and perspectives and possible analytical developments are discussed.

Migration of two antibiotics during resuspension under simulated wind-wave disturbances in a water-sediment system.

In this study, the migration of antibiotics (norfloxacin, NOR; and sulfamethoxazole, SMX) under simulated resuspension conditions across the sediment-water interface were quantified for two locations in China: point A, located in Meiliang Bay of Lake Taihu, and point B, located in Dapukou of Lake Taihu. The concentrations of suspended solids (SS) in the overlying water amounted to 100, 500, and 1000 mg/L during background, moderate, and strong simulated wind-wave disturbances, respectively. At each SS level, the initial concentrations of the two antibiotics were set to 1, 5, and 10 mg/L. The results showed that both resuspended SS and the initial concentration of antibiotics could influence the migration of NOR in the water-sediment system. Specifically, both higher SS and initial antibiotic concentrations were associated with higher rates of migration and accumulation of NOR from water to sediment. In contrast, the migration of SMX in the water-sediment system was not impacted by SS or initial antibiotic concentration. The adsorption capacities of sediments for NOR and SMX were significantly different at both locations, possibly reflecting differences in cation exchange capacity (CEC) and organic material (OM) contents. In general, higher CEC and OM values were found in sediments with a higher adsorption capacity for the antibiotics. When CEC and OM values of sediments were higher, the adsorption capacity reached up to 51.73 mg/kg. Large differences in the migration from water to sediment were observed for the two antibiotics, with NOR migration rates higher than those of SMX. The accumulation of NOR in surface sediment during resuspension was about 14 times higher than that of SMX. The main reason for this is that the chemical adsorption of NOR is seldom reversible. Overall, this study demonstrates that resuspension of NOR and SMX attached to sediments under simulated wind-wave disturbances can promote the migration of the antibiotics from water to sediment; these results could be useful for assessing the migration and fate of commonly used antibiotics in water-sediment systems.

In vitro dissolution testing of parenteral aqueous solutions and oily suspensions of paracetamol and prednisolone.

The number of intramuscularly applied dosage forms has been continuously increasing during the last decades. However, up to date no in vitro dissolution test method for parenteral dosage forms has been described in the Ph. Eur. or USP. It was the aim of this study to investigate dissolution test setups based on the compendial flow-through cell and the reciprocating holder for this purpose. Both apparatuses were equipped with dialysis membranes to accommodate the drug formulation. The suitability of the dissolution method was evaluated by comparing release profiles with blood level curves that were obtained previously in an in vivo study in rats by our group. Aqueous solutions and oily suspensions of paracetamol and prednisolone were tested in vitro that were also applied in the in vivo study. In the case of the aqueous solutions in which no formal dissolution occurs, transport from the applied depot across a dialysis membrane was investigated. While the drug transport across the dialysis membrane of both drugs in aqueous solution was similar in all applied test methods, differences in the release behavior of paracetamol and prednisolone as an oily suspension were observed. This was mainly due to sedimentation of the particles within the oily depot.

Stability of Allopurinol, Amitriptyline Hydrochloride, Carbamazepine, Domperidone, Isoniazid, Ketoconazole, Lisinopril, Naproxen, Paracetamol (Acetaminophen), and Sertraline Hydrochloride in SyrSpend SF PH4 Oral Suspensions.

Oral liquids are safe alternatives to solid dosage forms, notably for elderly and pediatric patients that present dysphagia. The use of ready-to-use suspending vehicles such as SyrSpend SF PH4 is a suitable resource for pharmacists as they constitute a safe and timesaving option that has been studied often. The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients (allopurinol 20 mg/mL; amitriptyline hydrochloride 10 mg/mL; carbamazepine 25 mg/mL; domperidone 5 mg/mL; isoniazid 10 mg/mL; ketoconazole 20 mg/mL; lisinopril 1 mg/mL; naproxen 25 mg/mL; paracetamol [acetaminophen] 50 mg/mL; and sertraline hydrochloride 10 mg/mL) compounded in oral suspensions using SyrSpend SF PH4 as the vehicle throughout the study period and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring the percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by high-performance liquid chromatography through a stability-indicating method. Methods were adequately validated. Forced-degradation studies showed that at least one parameter influenced the stability of the active pharmaceutical ingredients. All suspensions were assayed and showed active pharmaceutical ingredient contents between 90% and 110% during the 90-day study period. Although the forced-degradation experiments led to visible fluctuations in the chromatographic responses, the final preparations were stable in the storage conditions. The beyond-use dates of the preparations were found to be at least 90 days for all suspensions, both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients for different medical usages.

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

Assessment of the characterization of nonabsorbing nanoparticles in suspension from effective optical properties.

We analyze a method recently proposed to retrieve the size, refractive index, and concentration of particles in nonabsorbing nanofluids from measurements of the complex effective refractive index of two dilutions of the nanofluid [Opt. Lett.39, 559 (2014)]. The method uses simple formulas to retrieve the particles' parameters. First, we discuss precautions needed with the new method when inferring the refractive index of the particles from measurements of the imaginary part of the effective refractive index of two dilutions of the original nanofluid. Then we analyze the use of this methodology to obtain some average radius in the size of polydisperse suspensions and in the case of suspensions of weakly absorbing particles. We also perform an error analysis considering fixed errors in measurements and calculating the errors in the retrieved size, refractive index, and concentration of particles. Finally, we characterize experimentally nanofluids of polymeric particles fabricated of poly(methyl-methacrylate) (PMMA) and polystyrene (PS) for which we achieved an uncertainty of 5×10(-3) and 1×10(-2) in the determination of the particle refractive index, respectively, and a precision better than 3% in the determination of their radii.

[Analysis of ambient air suspensions in Karakan coalfield in Kouzbass].

The article covers results of studies concerning nano- and microparticles in atmospheric suspensions in snow collected in 11 points of Karakan coal extraction cluster (Kouzbass) in winter of 2011-2012. As a reference, a sample was taken on territory of Kouzbass botanical garden of Human Ecology Institute with RASc Siberian Division. All the points studied appeared to be polluted with technogenous suspensions--that proves high ecologic load on atmosphere over all territory of Kouzbass coalfield. Particles found in snow could be placed in decrement order: coal (up to 80%), natural minerals (mostly aluminosilicate and quartz) (up to 10%), vegetable detrital matter, unidentifiable technogenic particles, metals and their compounds (mostly Fe, Ba and Ti). Some areas appeared to frequently present microparticles containing rare-earth metals (rare-earth phosphates and alumophosphates prevail).

Coagulation of highly turbid suspensions using magnesium hydroxide: effects of slow mixing conditions.

Laboratory experiments were carried out to study the effects of slow mixing conditions on magnesium hydroxide floc size and strength and to determine the turbidity and total suspended solid (TSS) removal efficiencies during coagulation of highly turbid suspensions. A highly turbid kaolin clay suspension (1,213 ± 36 nephelometric turbidity units (NTU)) was alkalized to pH 10.5 using a 5 M NaOH solution; liquid bittern (LB) equivalent to 536 mg/L of Mg(2+) was added as a coagulant, and the suspension was then subjected to previously optimized fast mixing conditions of 100 rpm and 60 s. Slow mixing speed (20, 30, 40, and 50 rpm) and time (10, 20, and 30 min) were then varied, while the temperature was maintained at 20.7 ± 1 °C. The standard practice for coagulation-flocculation jar test ASTM D2035-13 (2013) was followed in all experiments. Relative floc size was monitored using an optical measuring device, photometric dispersion analyzer (PDA 2000). Larger and more shear resistant flocs were obtained at 20 rpm for both 20- and 30-min slow mixing times; however, given the shorter duration for the former, the 20-min slow mixing time was considered to be more energy efficient. For slow mixing camp number (Gt) values in the range of 8,400-90,000, it was found that the mixing speed affected floc size and strength more than the time. Higher-turbidity removal efficiencies were achieved at 20 and 30 rpm, while TSS removal efficiency was higher for the 50-rpm slow mixing speed. Extended slow mixing time of 30 min yielded better turbidity and TSS removal efficiencies at the slower speeds.

Asymmetrical flow field-flow fractionation analysis of water suspensions of polymer nanofibers synthesized via RAFT-mediated emulsion polymerization.

The aim of this work is to present a method based on asymmetric flow-field-flow-fractionation coupled on-line to a static light scattering (AF4-UV-SLS) detector to characterize self-assembled nanofibers (NFs). The method developed herein allows the determination of both the length distribution of the NFs as well as the distribution in terms of aggregation number per unit length (Agg). Given the remaining synthetic challenges of better controlling the structural homogeneity and particle dimensions, the NF length and aggregation number per unit length are becoming essential for the improvement and control of their chemical processes and a better understanding of their properties. The results obtained with this AF4-UV-SLS method indicate that a well-resolved NF length distribution characterization and Agg determination were attained. These results provide critical information concerning the physical properties of the investigated NFs and open the door to the characterization of new self-assembled polymers with various asymmetrical architectures.

Extemporaneous clobazam suspensions for paediatric use prepared from commercially available tablets and pure drug

Objective: Two clobazam aqueous suspensions for paediatric oral usage (5 mg/ml) were investigated to determinate its physicochemical stability under different storage conditions. Method: Formulations were stored at 4 and 25 oC and the clobazam content was determined by High Performance Liquid Chromatography. Each sample was analyzed by triplicate at different time points (0, 7, 14, 28 and 56 days). Results: Liquid suspensions were successfully formulated from pure drug and commercially available tablets. In both cases, samples showed suitable physical stability. Clobazam was chemically stable in aqueous suspension during the 56 days of the study at the two storage temperatures. Conclusions: All the tried oral liquid formulations can be conserved at 4 and 25 oC at least 56-day period (AU)

Objetivo: Dos suspensiones orales acuosas de clobazam para uso pediátrico (5 mg/ml) fueron evaluadas para determinar su estabilidad fisicoquimica bajo diferentes condiciones de almacenamiento. Métodos: Las formulaciones fueron conservadas a 4 y 25 oC y el contenido de clobazam fue determinado mediante Cromatografía Líquida de Alta Performance. Cada una de las muestras fue analizada por triplicado a diferentes tiempos (0, 7, 14, 28 y 56 días). Resultados: Las suspensiones fueron formuladas satisfactoriamente a partir del principio activo puro y de comprimidos disponibles comercialmente. En ambos casos, las muestras presentaron una adecuada estabilidad física. El clobazam fue químicamente estable en las suspensiones acuosas durante los 56 días de duración del estudio a las dos temperaturas elegidas para su conservación. Conclusiones: Todas las formulaciones orales líquidas formuladas y evaluadas en este estudio pueden ser conservadas a 4 y 25 oC por al menos 56 días (AU)

Simultaneous and rapid detection of multiple pesticide and veterinary drug residues by suspension array technology.

Suspension array technology is proposed for the simultaneous quantitative determination of seven kinds of pesticide and veterinary drug residues, namely, atrazine, chloramphenicol, carbaryl, clenbuterol, 17-ß-estradiol, imidacloprid, and tylosin. The assay is simple and can be accomplished within 2h without repeated pumping and washing steps unlike conventional suspension arrays. The hapten-protein conjugate-coated beads bind to their complementary biotinylated antibodies using a competitive immunoassay format. The coefficients of determination R(2) for six targets were greater than 0.992, whereas that for atrazine was 0.961, which indicate good logistic correlations. The dynamic ranges for the seven targets in the 7-plex assay ranged from 2 log units to 4 log units(1.60×10(0)-1.64×10(3), 5.12×10(-2)-1.60×10(2), 1.00×10(0)-3.13×10(3), 4.00×10(-1)-4.10×10(2), 4.00×10(-1)-4.10×10(2), 5.12×10(-2)-1.60×10(2), and 2.00×10(0)-4.00×10(2)ngmL(-1)). The minimum detection concentrations of chloramphenicol, carbaryl, clenbuterol and 17-ß-estradiol in the suspension array (0.05, 1.00, 0.40 and 0.40 ng mL(-1)) were lower than the corresponding limits of detection (0.25, 6.60, 24.23 and 13.96 ng mL(-1)) of using an indirect competitive enzyme-linked immunosorbent assay. Environmental scanning electron microscope was employed to characterize the bead surface, which directly confirmed the reactions on the beads. The suspension array is more flexible and feasible than ELISA for the fast quantitative analysis of pesticide and veterinary drug residues.

Determination of the volume scattering function of aqueous particle suspensions with a laboratory multi-angle light scattering instrument.

We describe a methodology for determining the volume scattering function ß(ψ) of aqueous particle suspensions from measurements with a laboratory multi-angle light scattering instrument called DAWN (Wyatt Technology Corporation). In addition to absolute and angular calibration, the key component of the method is the algorithm correcting for reflection errors that reduce the percent error in ß(ψ) from as much as ~300% to <13% at backward scattering angles. The method is optimized and tested with simulations of three-dimensional radiative transfer of exact measurement geometry including the key components of the instrument and also validated experimentally using aqueous suspensions of polystyrene beads. Example applications of the method to samples of oceanic waters and comparisons of these measurements with results obtained with other light scattering instruments are presented.

Interaction of liposomal formulations of meta-tetra(hydroxyphenyl)chlorin (temoporfin) with serum proteins: protein binding and liposome destruction.

mTHPC is a non polar photosensitizer used in photodynamic therapy. To improve its solubility and pharmacokinetic properties, liposomes were proposed as drug carriers. Binding of liposomal mTHPC to serum proteins and stability of drug carriers in serum are of major importance for PDT efficacy; however, neither was reported before. We studied drug binding to human serum proteins using size-exclusion chromatography. Liposomes destruction in human serum was measured by nanoparticle tracking analysis (NTA). Inclusion of mTHPC into conventional (Foslip(®)) and PEGylated (Fospeg(®)) liposomes does not affect equilibrium serum protein binding compared with solvent-based mTHPC. At short incubation times the redistribution of mTHPC from Foslip(®) and Fospeg(®) proceeds by both drug release and liposomes destruction. At longer incubation times, the drug redistributes only by release. The release of mTHPC from PEGylated vesicles is delayed compared with conventional liposomes, alongside with greatly decreased liposomes destruction. Thus, for long-circulation times the pharmacokinetic behavior of Fospeg(®) could be influenced by a combination of protein- and liposome-bound drug. The study highlights the modes of interaction of photosensitizer-loaded nanovesicles in serum to predict optimal drug delivery and behavior in vivo in preclinical models, as well as the novel application of NTA to assess the destruction of liposomes.

Suspension flow in microfluidic devices--a review of experimental techniques focussing on concentration and velocity gradients.

Microfluidic devices are an emerging technology for processing suspensions in e.g. medical applications, pharmaceutics and food. Compared to larger scales, particles will be more influenced by migration in microfluidic devices, and this may even be used to facilitate segregation and separation. In order to get most out of these completely new technologies, methods to experimentally measure (or compute) particle migration are needed to gain sufficient insights for rational design. However, the currently available methods only allow limited access to particle behaviour. In this review we compare experimental methods to investigate migration phenomena that can occur in microfluidic systems when operated with natural suspensions, having typical particle diameters of 0.1 to 10 µm. The methods are used to monitor concentration and velocity profiles of bidisperse and polydisperse suspensions, which are notoriously difficult to measure due to the small dimensions of channels and particles. Various methods have been proposed in literature: tomography, ultrasound, and optical analysis, and here we review and evaluate them on general dimensionless numbers related to process conditions and channel dimensions. Besides, eleven practical criteria chosen such that they can also be used for various applications, are used to evaluate the performance of the methods. We found that NMR and CSLM, although expensive, are the most promising techniques to investigate flowing suspensions in microfluidic devices, where one may be preferred over the other depending on the size, concentration and nature of the suspension, the dimensions of the channel, and the information that has to be obtained. The paper concludes with an outlook on future developments of measurement techniques.

Dependence of Cu, Pb and Zn remobilization on physicochemical properties of marine sediments.

The resuspension of 65 marine sediments was simulated in the laboratory with elutriates from 30 different sites from the north coast of Spain. The partitioning of Cu, Pb and Zn between sediment and elutriate was studied as a function of different physicochemical characteristics of the sediment: organic matter (OM), fine fraction (FF), redox potential and acid volatile sulfides (AVS). Mean remobilization factors (RF) -calculated as metal concentration in the elutriate (µg/L) divided by metal concentration in the sediment (µg/g dry weight)- were 0.072 for Cu, 0.012 for Pb and 0.071 for Zn. Remobilization of Pb was significantly lower than that of Cu and Zn. Although AVS, OM and FF presented a strong intercorrelation, OM explained great part of the variability on Cu and Pb remobilization while AVS did it for Zn. A multiple regression model considering both OM and AVS explained slightly better the remobilization of Pb and Cu, but not that of Zn.

Mass-specific scattering cross sections of suspended sediments and aggregates: theoretical limits and applications.

The spectral mass-specific scattering cross section σ[PIM](λ) is most important for the remote sensing inversion of the concentration of suspended mineral matter in the coastal ocean. This optical parameter is also important in optical theory and therefore the theoretical limits of this parameter are important. There are differing reports in the literature on the magnitude of σ[PIM](λ) and its spectral slope in different coastal ocean systems. To account for and predict these differences, I have applied a model of the size distribution of primary suspended mineral particles and aggregates of these particles to theoretical calculations of σ[PIM](λ). I utilized a model of mineral particle aggregates by Khelifa and Hill [Khelifa, A. and P.S. Hill, J. Hydraul. Res. 44, 390 (2006)] and Latimer's optical model of aggregates [Latimer, P., Appl. Opt. 24, 3231, (1985)]. I have been able to account for the variations in magnitude and spectral slope of σ[PIM](λ). This analysis will apply to not only inverting the concentration of suspended mineral matter but also provides the basis for inverting the processes of coagulation and aggregation of primary mineral particles in determining sedimentation rates, budgets, etc.

Critical evaluation and guidance for using the Coulter method for counting subvisible particles in protein solutions.

In this paper, we evaluate the suitability of Coulter method for detecting and quantifying subvisible particles in protein solutions and compare results with other particle-counting technologies. The effects of key instrument and operational parameters such as aperture diameter, solution conductivity, and cleaning procedures are demonstrated. Degraded and nondegraded intravenous immunoglobulin and human serum albumin were chosen as model proteins and sample types for this evaluation. Multisizer™4 was able to obtain reproducible and linear particle counts; however, customized analysis and cleaning procedures are needed depending on the protein analyzed and the sample type (degraded or nondegraded). The Coulter method consistently detected more particles than micro-flow imaging and light obscuration. The presence of translucent particles likely accounts for this observation because detection by the Coulter method does not depend on the optical properties of the particles or solution.

Development and validation of a reversed-phase column liquid chromatographic method for the determination of five cephalosporins in pharmaceutical preparations.

A new, simple, rapid, and precise RP-HPLC method has been developed and validated for the determination of five cephalosporins, namely, cefalexin, cefoperazone, ceftriaxone, ceftazidime, and cefepime. The method has been applied successfully for simultaneous determination of cefalexin in a binary mixture with sodium benzoate in a suspension, and cefoperazone in a binary mixture with sulbactam in vials. Chromatographic separation was achieved on a Waters microBondapak C18 column (250 x 4.6 mm id, 10 pm particle size) using the mobile phase monobasic potassium phosphate (50 mM, pH 4.6)-acetonitrile (80 + 20, v/v) with UV detection. A flow rate of 1 mL/min was applied. Linearity, accuracy, and precision were found to be acceptable over the concentration range of 30-300, 3-30, and 15-120 microg/mL for the studied cephalosporins, sodium benzoate, and sulbactam, respectively. The optimized method proved to be specific, robust, and accurate for QC of the cited drugs in their pharmaceutical preparations.

Reference material development for calibration and verification of image-based particle analyzers.

The need is well recognized for suitable reference populations for calibrating and verifying the size and concentration accuracy of particle analysis instruments for use in the measurement of suspended protein particles in biopharmaceuticals. Polystyrene bead standards are normally used as a reference material for calibrating and validating particle analyzers. However, these standards, unlike protein particles, are easily detected and do not challenge the sensitivity of optical instruments. Groups of instruments verified only with beads can still exhibit significant differences in measuring concentrations of more challenging protein particles. To minimize these and obtain consistent concentration measurements between instruments, reference populations must closely resemble protein aggregates in possessing high transparency and a refractive index close to typical protein matrix fluids. This paper describes work on evaluating a promising reference candidate and the use of this to harmonize the performance of Micro-Flow Imaging instruments. Results show that use of a suitable reference population can significantly increase measurement consistency when multiple instruments are used to characterize the same protein particle suspension.