Synergetic reinforcing effect of graphene oxide and nanosilver on carboxymethyl cellulose/sodium alginate nanocomposite films: Assessment of physicochemical and antibacterial properties.

Incorporating single or combined nanofillers in polymeric matrices is a promising approach for developing antimicrobial materials for applications in wound healing and packaging etc. This study reports a facile fabrication of antimicrobial nanocomposite films using biocompatible polymers sodium carboxymethyl cellulose (CMC) and sodium alginate (SA) reinforced with nanosilver (Ag) and graphene oxide (GO) using the solvent casting approach. Eco-friendly synthesis of Ag nanoparticles within a size range of 20-30 nm was carried out within the polymeric solution. GO was introduced into the CMC/SA/Ag solution in different weight percentages. The films were characterized by UV-Vis, FT-IR, Raman, XRD, FE-SEM, EDAX, and TEM. The results indicated the enhanced thermal and mechanical performance of CMC/SA/Ag-GO nanocomposites with increased GO weight %. The antibacterial efficacy of the fabricated films was evaluated on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The CMC/SA/Ag-GO2% nanocomposite exhibited the highest zone of inhibition of 21.30 ± 0.70 mm against E. coli and 18.00 ± 1.00 mm against S. aureus. The CMC/SA/Ag-GO nanocomposites exhibited excellent antibacterial activity as compared to CMC/SA and CMC/SA-Ag due to the synergetic bacterial growth inhibition activities of the GO and Ag. The cytotoxic activity of the prepared nanocomposite films was also assessed to investigate their biocompatibility.

Sequestration and toxicological assessment of emerging contaminants with polypyrrole modified carboxymethyl cellulose (CMC/PPY): Case of ibuprofen pharmaceutical drug.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug released into water bodies causing toxic biological effects on living organisms. The current study aims to eliminate IBU from aqueous solutions by a novel carboxymethylcellulose/polypyrrole (CMC/PPY) composite with high removal efficiency. Pyrrole was polymerized to polypyrrole whose average size was about 20 nm on the CMC surface. The maximum removal percentage of IBU by CMC/PPY composite was optimized at initial concentration 10 mg/L, dosage 0.02 g, and pH 7 with adsorption capacity of 72.30 (mg/g) and removal of 83.17 %. IBU adsorption onto CMC/PPY theoretically fits into the Langmuir isotherm and Elovich-kinetic models. Fish and Phytotoxicity assessment were performed with zebrafish and seeds of Vigna mungo (VM) and Vigna radiata (VR). The toxicity study reveals that before adsorption, IBU shows high toxicity towards the zebrafish mortality (33 %), growth inhibition (58.52 % for VM, 60.84 % for VR), and germination (86.66 % for VM and 90 % for VR). As CMC/PPY adsorbs IBU, toxicity drastically decreases. Before adsorption, LC50 was 233.02 mg/L. After adsorption, the LC50 increases to 2325.07 mg/L as IBU molecules get adsorbed by CMC/PPY. These findings show the feasibility of preparing CMC/PPY composite to effectively remove pharmaceutical pollutant IBU from aqueous solutions with their toxicological assessment.

Novel low-cost carboxymethyl cellulose microspheres with excellent fertilizer absorbency and release behavior for saline-alkali soil.

Saline-alkali soil and fertilizer loss severely restrict agriculture on the Songnen Plain in China. To resolve this problem, carboxymethyl cellulose immobilized slow-release fertilizer microspheres (CFM) with homogeneity pore structure, high porosity, biodegradable biological macromolecules and excellent fertilizer absorbency were synthesized by the combination of inverse emulsion polymerization and microfluidic method. By optimizing the synthesis conditions, the water absorption of CFM reached 8725 g g-1 in deionized water. The absorbency behaviors of CFM were highly sensitive to pH, ionic strength, and ionic species. In 5 g L-1 urea solution, the adsorption capacity of CFM was 3342.84 g g-1. The CFM showed excellent urea retention at 80 °C for 5 h and sustained release performance in soil. Besides, degradation rate of CFM was closed to 98.2% in Aspergillus niger at the third day. CFM had the advantages of high pH sensitivity, salt resistance, and good fertilizer absorbency and retention. Therefore, it will be prospecting fertilizer sustained release agent in agriculture.

Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.

The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y1), percentage friability (Y2), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher C max and (AUC0-12) and shorter T max than those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.

ASSESSMENT OF A STABLE COSMETIC PREPARATION BASED ON ENZYMATIC INTERESTERIFIED FAT, PROPOSED IN THE PREVENTION OF ATOPIC DERMATITIS.

Atopic dermatitis is one of the most common skin disorders seen in infants, children and adults. Proper prevention might slow the atopic symptoms. The purpose of the work was a sensory analysis, an evaluation of moistening properties and stability of emulsions based on an enzymatic interesterified fat blend (mutton tallow and walnut oil) and homogenized at different revolutions and different contents of thickener. The emulsions were evaluated with respect to sensory and skin moisturizing properties by 78 respondents. Stability tests, particle size, distribution, dispersity index, morphology structure of the emulsions were determinated too. Taking into consideration all properties of the emulsions, emulsion IV (containing 0.9 g carboxymethyl cellulose and homogenized at 18000 rpm) and emulsion V (1.5 g of carboxymethyl cellulose and homogenized at 24000 rpm) were found to be of optimum composition. The emulsions exhibited good stability, were highly rated in sensory terms and displayed optimum moistening properties. It has been proven that model emulsions based on interesterified fats containing partial acylglicerols, with optimum carboxymethyl cellulose content and specific revolutions at the time of homogenization are an opportunity for developing preparations targeted at skins requiring special care (e.g., with atopic dermatitis or psoriasis). The work proved the use of enzymatic process to create the emulsifier, which represents the innovative contribution of this work. Also it showed an additional application of enzymatic interesterified fats which since has been used only in food industries.

Quantitative surface topography assessment of directly compressed and roller compacted tablet cores using photometric stereo image analysis.

Surface topography, in the context of surface smoothness/roughness, was investigated by the use of an image analysis technique, MultiRay™, related to photometric stereo, on different tablet batches manufactured either by direct compression or roller compaction. In the present study, oblique illumination of the tablet (darkfield) was considered and the area of cracks and pores in the surface was used as a measure of tablet surface topography; the higher a value, the rougher the surface. The investigations demonstrated a high precision of the proposed technique, which was able to rapidly (within milliseconds) and quantitatively measure the obtained surface topography of the produced tablets. Compaction history, in the form of applied roll force and tablet punch pressure, was also reflected in the measured smoothness of the tablet surfaces. Generally it was found that a higher degree of plastic deformation of the microcrystalline cellulose resulted in a smoother tablet surface. This altogether demonstrated that the technique provides the pharmaceutical developer with a reliable, quantitative response parameter for visual appearance of solid dosage forms, which may be used for process and ultimately product optimization.

Assessment of powder blend uniformity: Comparison of real-time NIR blend monitoring with stratified sampling in combination with HPLC and at-line NIR Chemical Imaging.

Scope of the study was (1) to develop a lean quantitative calibration for real-time near-infrared (NIR) blend monitoring, which meets the requirements in early development of pharmaceutical products and (2) to compare the prediction performance of this approach with the results obtained from stratified sampling using a sample thief in combination with off-line high pressure liquid chromatography (HPLC) and at-line near-infrared chemical imaging (NIRCI). Tablets were manufactured from powder blends and analyzed with NIRCI and HPLC to verify the real-time results. The model formulation contained 25% w/w naproxen as a cohesive active pharmaceutical ingredient (API), microcrystalline cellulose and croscarmellose sodium as cohesive excipients and free-flowing mannitol. Five in-line NIR calibration approaches, all using the spectra from the end of the blending process as reference for PLS modeling, were compared in terms of selectivity, precision, prediction accuracy and robustness. High selectivity could be achieved with a "reduced" approach i.e. API and time saving approach (35% reduction of API amount) based on six concentration levels of the API with three levels realized by three independent powder blends and the additional levels obtained by simply increasing the API concentration in these blends. Accuracy and robustness were further improved by combining this calibration set with a second independent data set comprising different excipient concentrations and reflecting different environmental conditions. The combined calibration model was used to monitor the blending process of independent batches. For this model formulation the target concentration of the API could be achieved within 3 min indicating a short blending time. The in-line NIR approach was verified by stratified sampling HPLC and NIRCI results. All three methods revealed comparable results regarding blend end point determination. Differences in both mean API concentration and RSD values could be attributed to differences in effective sample size and thief sampling errors. This conclusion was supported by HPLC and NIRCI analysis of tablets manufactured from powder blends after different blending times. In summary, the study clearly demonstrates the ability to develop efficient and robust quantitative calibrations for real-time NIR powder blend monitoring with a reduced set of powder blends while avoiding any bias caused by physical sampling.

Real-time assessment of granule densification in high shear wet granulation and application to scale-up of a placebo and a brivanib alaninate formulation.

Real-time monitoring and control of high shear wet granulation (HSWG) using process analytical technologies is crucial to process design, scale-up, and reproducible manufacture. Although significant progress has been made in real-time measurement of granule size distribution using focused beam reflectance measurement (FBRM), real-time in-line assessment of granule densification remains challenging. In this study, a drag force flow (DFF) sensor was developed and used to probe wet mass consistency in real-time. In addition, responses from FBRM and DFF sensors were compared to assess complementarity of information on granulation progress from the two probes. A placebo and a brivanib alaninate formulation were granulated with different concentrations of binder or water, respectively, while measuring granule size growth, densification, and DFF sensor response. The DFF sensor was able to quantitatively characterize with high resolution a response of wet mass consistency distinct from granule size distribution. The wet mass consistency parameter correlated well with granule densification, which was shown as a critical material attribute that correlated with tablet dissolution. In addition, application of DFF sensor to scale-up of granulation was demonstrated. These results showed the value of wet mass consistency measurement using DFF for WG monitoring and control.

A new apparatus for real-time assessment of the particle size distribution of disintegrating tablets.

The aim of this study is the introduction of a novel apparatus that is capable of continuously measuring the particle size reduction of disintegrating tablets and analysis of the obtained results. The apparatus is constructed such that no particles pass directly through the pumping system. Thereby, the overall energy input into the particle suspension is reduced, and continuous measurement is possible without rapid destruction of the generated particles. The detected particle sizes at the beginning and at the end of the measurement differ greatly, depending on the applied disintegrant. The median particle sizes at the end of the measurement vary between 621.5 and 178.0 µm for different disintegrants. It is demonstrated that the particle size reduction follows an exponential function and that the fit parameters can be used to describe the disintegration behavior. A strong correlation between the median particle size of crospovidone disintegrants and generated particle size of the tablets is observed. This could be due to a more homogeneous distribution of the disintegrant particles in the tablets. Similar trends are observed for sodium starch glycolate and croscarmellose sodium. The new apparatus provides an innovative method to describe disintegrant effectiveness and efficiency.

Assessment of disintegrant efficacy with fractal dimensions from real-time MRI.

An efficient disintegrant is capable of breaking up a tablet in the smallest possible particles in the shortest time. Until now, comparative data on the efficacy of different disintegrants is based on dissolution studies or the disintegration time. Extending these approaches, this study introduces a method, which defines the evolution of fractal dimensions of tablets as surrogate parameter for the available surface area. Fractal dimensions are a measure for the tortuosity of a line, in this case the upper surface of a disintegrating tablet. High-resolution real-time MRI was used to record videos of disintegrating tablets. The acquired video images were processed to depict the upper surface of the tablets and a box-counting algorithm was used to estimate the fractal dimensions. The influence of six different disintegrants, of different relative tablet density, and increasing disintegrant concentration was investigated to evaluate the performance of the novel method. Changing relative densities hardly affect the progression of fractal dimensions, whereas an increase in disintegrant concentration causes increasing fractal dimensions during disintegration, which are also reached quicker. Different disintegrants display only minor differences in the maximal fractal dimension, yet the kinetic in which the maximum is reached allows a differentiation and classification of disintegrants.

In vitro assessment of artificial saliva formulations on initial enamel erosion remineralization.

OBJECTIVES: Various formulations of artificial saliva are present in the literature and little guidance is available on the standardization of type of saliva for use in in vitro protocols for erosive studies. The aim of this study was to evaluate the remineralizing capacity of different formulations of artificial saliva on initial enamel erosive lesion. METHODS: Bovine enamel blocks were subjected to short-term acidic exposure by immersion in citric acid 0.05 M (pH 2.5) for 15s, resulting in surface softening without tissue loss. Then 90 selected eroded enamel blocks were randomly and equally divided into 6 groups according to saliva formulation (n=15): Saliva 1 (contain mucin); Saliva 2 (Saliva 1 without mucin); Saliva 3; Saliva 4; Saliva 5 (contain sodium carboxymethyl cellulose) and control (C) (deionized water). After demineralization enamel blocks were subjected to remineralization by immersion in the saliva's formulations for 2h. Enamel remineralization was measured by superficial hardness test (% superficial hardness change). The data were tested using ANOVA and Tukey's test (p<0.05). RESULTS: All the tested formulations of artificial saliva resulted in significantly higher enamel remineralization compared to control (p<0.001). Saliva 3 showed higher percentage of enamel remineralization than Saliva 5 (p<0.05). CONCLUSIONS: Besides the variety of artificial saliva for erosion in vitro protocols, all the formulations tested were able to partially remineralize initial erosive lesions.

Mechanochemical activation of vincamine mediated by linear polymers: assessment of some "critical" steps.

The aim of the research was to investigate three "critical steps" that deserve particular attention during the mechanochemical activation of vincamine. The first step consisted in the selection of the best polymeric carrier/most affine stabiliser between linear PVP and NaCMC by using the GRID and the GRID based AutoDock software packages which permit to calculate their surface features and interactions. Moreover, the calculation of the partial and total solubility parameters supported the results obtained by GRID and AutoDock software. Then, after the selection of linear PVP-K30 as the suitable carrier, the influence of process and formulation variables on the amorphisation degree and solubility enhancement was studied, to select the most suitable process conditions and formulation parameters. Subsequently, the best performing samples were widely characterised using XRPD, TEM and SSNMR (including the proton relaxation ((1)H T1 NMR) time) techniques. These studies highlighted that all the coground samples were nanocrystalline solid dispersions indicating a dramatic difference between the amorphisation capacities of linear PVP-K30 and cross-linked PVP, used in previous analogous experiences. In particular, (13)C, (15)N and (1)H T1 NMR data point to a description of the system as a dispersion of nanocrystals in the polymer. In these dispersions vincamine is in a disordered crystalline state due to extensive interactions and contacts with PVP-K30 but the main hydrogen bonding motif characterising its packing remains. Again, differently from cross-linked PVP, dissolution studies revealed that linear PVP-K30 was able to promote a complete in vitro solubilisation of vincamine in some coground samples. What is more important, by using a linear polymer, drug-to-polymer and milling time variables appeared less influent on the solid state and in vitro properties of the composites. Finally, stability studies conducted for a period of 1year highlighted the high physical stability of the selected samples.

Synthesis, characterization and in vitro assessment of the magnetic chitosan-carboxymethylcellulose biocomposite interactions with the prokaryotic and eukaryotic cells.

Preparation and characterization of CS/Fe(3)O(4)/CMC composite scaffolds including the morphology, crystallinity, and the in vitro efficacy as antibiotic delivery vehicles as well as their influence on the eukaryotic cells are reported. The results demonstrated that the magnetic polymeric composite scaffolds are exhibiting structural and functional properties that recommend them for further applications in the biomedical field. They improve the activity of currently used antibiotics belonging to penicillins, macrolides, aminoglycosides, rifampicines and quinolones classes, representing potential macromolecular carriers for these antimicrobial substances, to achieve extracellular and intracellular targets. The obtained systems are not cytotoxic and do not influence the eukaryotic HCT8 cell cycle, representing potential tools for the delivery of drugs in a safe, effective and less expensive manner.

Functional assessment of four types of disintegrants and their effect on the spironolactone release properties.

Spironolactone is a drug derived from sterols that exhibits an incomplete oral absorption due to its low water solubility and slow dissolution rate. In this study, formulations of spironolactone with four disintegrants named as croscarmellose sodium, crospovidone, sodium starch glycolate and microcrystalline cellulose II (MCCII) were conducted. The effect of those disintegrants on the tensile strength, disintegration time and dissolution rate of spironolactone-based compacts was evaluated using a factorial design with three categorical factors (filler, lubricant, and disintegrant). The swelling values, water uptake and water sorption studies of these disintegrants all suggested that MCCII compacts disintegrate by a wicking mechanism similar to that of crospovidone, whereas a swelling mechanism was dominant for sodium starch glycolate and croscarmellose sodium. The disintegration time of MCCII and sodium starch glycolate remained unchanged with magnesium stearate. However, this lubricant delayed the disintegration time of crospovidone and croscarmellose sodium. MCCII presented the fastest disintegration time independent of the medium and lubricant employed. The water sorption ratio and swelling values determined sodium starch glycolate followed by croscarmellose sodium as the largest swelling materials, whereas crospovidone and MCCII where the least swelling disintegrants. The swelling property of sodium starch glycolate and croscarmellose sodium was strongly affected by the medium pH. The disintegration time of spironolactone compacts was faster when starch was used as a filler due to the formation of soft compacts. In this case, the type of filler employed rather than the disintegrant had a major effect on the disintegration and dissolution times of spironolactone.

Supramolecular assemblies of lipid-coated polyelectrolytes.

We reveal the existence of a general class of supramolecular assemblies made up of lipid-coated polyelectrolytes including the celebrated lipid-nucleic acid complexes. With the aid of high-resolution cryo-electron microscopy, we unveil the nanoscale internal organization of assemblies generated with a wide range of synthetic and biological polyelectrolytes, several of them being investigated in this context for the first time, namely, poly(styrene sulfonic acid), carboxylmethylcellulose, and filamentous actin. Using an original coarse-grained model representing lipid-coated polyelectrolytes as semiflexible tubes, we thoroughly explored the morphologies resulting from the self-assembly process as a function of tube lengths and rigidities; the computed structures are fully consistent with the experimental observations. In particular, we found a strong extension of the correlation range of the order parameter as the rigidity of the lipid-coated polyelectrolytes increases. Electrostatic interactions provide a stabilizing mechanism leading to finite-size equilibrium assemblies. These assemblies may constitute a generic route for interfacing polyelectrolytes to living cells to perform gene delivery, for instance.

Risk assessment of premature drug release during wet granulation of ordered mesoporous silica loaded with poorly soluble compounds itraconazole, fenofibrate, naproxen, and ibuprofen.

In this study, the potential of wet granulation of ordered mesoporous silica (OMS) material was evaluated to assess the risk of premature drug release during processing and to improve the bulk powder flow properties and compactibility for the development of an immediate release oral dosage form. The poorly water soluble model compounds, itraconazole, fenofibrate, naproxen, and ibuprofen were loaded into the model OMS, COK-12, and granulated using a polyvinylpyrrolidone (PVP) binder solution. Preliminary assessments were made with itraconazole loaded COK-12 to study the effects of the initial drug load, binder concentration, binder addition rate, and granulation temperature on premature drug release. Comparison to pure COK-12 revealed particle size enlargement and enhanced powder flow based on Carr Index and Hausner Ratio results. Following compression to 120 MPa, the compactibility of the granulated material also improved when compared to the untreated COK-12. In vitro release of itraconazole from the compressed granulated material was assessed with and without the disintegrant, croscarmellose sodium. Incorporation of 2.4 wt. croscarmellose sodium prior to compression successfully recovered the slight release loss following compression. To assess premature drug release, developments made with itraconazole loaded COK-12 were applied to loaded fenofibrate, naproxen, and ibuprofen. Results from modulated differential scanning calorimetry (MDSC) indicated that the risk of premature drug release during wet granulation was primarily compound dependent. These findings highlight challenges in preparation for a successful manufacturing process of OMS based formulations.

A colorimetric sensor for determination of cysteine by carboxymethyl cellulose-functionalized gold nanoparticles.

A simple and sensitive colorimetric method for cysteine detection was established based on the carboxymethyl cellulose-functionalized gold nanoparticles (CMC-AuNPs). The nanoparticles were directly synthesized with sodium carboxymethyl cellulose by a simple approach, which would protect particles against salt-induced aggregation. Then the CMC-AuNPs solution exhibited a high colorimetric selectivity to cysteine. The assay results indicated that the introduction of cysteine could induce the aggregation of the colloidal solutions at the presence of sodium chloride, displaying changes in color and in UV-vis absorption spectra. Thus an exceptionally simple, rapid method for detecting cysteine was obtained at the linear range of 10.0-100.0 microM with the relative coefficient of 0.997. The proposed method possessed the advantages of simplicity and sensitivity, and was applied to real urine sample detection. The results were satisfying and the proposed method was especially appropriate for detection of cysteine in biological samples.

Field assessment of carboxymethyl cellulose stabilized iron nanoparticles for in situ destruction of chlorinated solvents in source zones.

This study pilot-tested carboxymethyl cellulose (CMC) stabilized zero-valent iron (ZVI) nanoparticles (with a trace amount of Pd catalyst) for in situ destruction of chlorinated ethenes such as perchloroethylene (PCE) and trichloroethylene (TCE) and polychlorinated biphenyls (PCBs) that had been in groundwater for decades. The test site was located in a well-characterized secondary source zone of PCBs and chlorinated ethenes. Four test wells were installed along the groundwater flow direction (spaced 5 ft apart), including one injection well (IW), one up-gradient monitoring well (MW-3) and two down-gradient monitoring wells (MW-1 and MW-2). Stabilized nanoparticle suspension was prepared on-site and injected into the 50-ft deep, unconfined aquifer. Approximately 150 gallons of 0.2 g/L Fe-Pd (CMC = 0.1 wt%, Pd/Fe = 0.1 wt%) was gravity-fed through IW-1 over a 4-h period (Injection #1). One month later, another 150 gallons of 1.0 g/L Fe-Pd (CMC = 0.6 wt%, Pd/Fe = 0.1 wt%) was injected into IW-1 at an injection pressure <5 psi (Injection #2). When benchmarked against the tracer, approximately 37.4% and 70.0% of the injected Fe was detected in MW-1 during injection #1 and #2, respectively, confirming the soil mobility of the nanoparticles through the aquifer, and higher mobility of the particles was observed when the injection was performed under higher pressure. Rapid degradation of PCE and TCE was observed in both MW-1 and MW-2 following each injection, with the maximum degradation being observed during the first week of the injections. The chlorinated ethenes concentrations gradually returned to their pre-injection levels after approximately 2 weeks, indicating exhaustion of the ZVI's reducing power. However, the injection of CMC-stabilized nanoparticle and the abiotic reductive dechlorination process appeared to have boosted a long-term in situ biological dechlorination thereafter, which was evidenced by the fact that PCE and TCE concentrations showed further reduction after two weeks. After 596 days from the first injection, the total chlorinated ethenes concentration decreased by about 40% and 61% in MW-1 and MW-2, respectively. No significant long-term reduction of PCB 1242 was observed in MW-1, but a reduction of 87% was evident in MW-2. During the 596 days of testing, the total concentrations of cis-DCE (dichloroethylene) and VC (vinyl chloride) decreased by 20% and 38% in MW-1 and MW-2, respectively. However, the combined fraction of cis-DCE and VC in the total chlorinated ethenes (PCE, TCE, cis-DCE and VC) increased from 73% to 98% and from 62% to 98%, respectively, which supports the notion that biological dechlorination of PCE and TCE was active. It is proposed that CMC-stabilized ZVI-Pd nanoparticles facilitated the early stage rapid abiotic degradation. Over the long run, the existing biological degradation process was boosted with CMC as the carbon source and hydrogen from the abiotic/biotic processes as the electron donor, resulting in the sustained enhanced destruction of the chlorinated organic chlorinated ethenes in the subsurface.

Assessment of the influence factors on in vitro testing of nasal sprays using Box-Behnken experimental design.

The purpose of the research was to investigate the influences of actuation parameters and formulation physical properties on nasal spray delivery performance using design of experiment (DOE) methodology. A 3-level, 4-factor Box-Behnken design with a total of 27 experimental runs was used in this study. Nine simulated aqueous formulations with different viscosities and surface tensions were prepared using carboxymethylcellulose sodium (CMC, gelling agent) and Tween80 (surfactant) each at three concentration levels. Four factors, actuation stroke length, actuation velocity, concentration of gelling agent, and concentration of surfactant were investigated for their influences on measured responses of shot weight, spray pattern, plume geometry and droplet size distribution (DSD). The models based on data from the DOE were then optimized by eliminating insignificant terms. Pfeiffer nasal spray pump units filled with the simulated formulations were used in the study. Nasal pump actuation stroke length exerts a strong, independent influence on shot weight, and also slightly affects spray pattern and plume geometry. Actuation velocity and concentration of gelling agent have significant effects on spray pattern, plume geometry and DSD, in a complicated manner through interaction terms. Concentration of surfactant has little, if any, influence on nasal spray characteristics. Results were fitted to quadratic models describing the inherent relationships between the four factors evaluated and nasal spray performance. The DOE study helped us to identify the source of variability in nasal spray product performance, and obtained better understanding in how to control the variability. Moreover, the quadratic models developed from the DOE study quantitatively describe the inherent relationships between the factors and nasal spray performance characteristics. With the assistance of the response surfaces developed from the DOE model, the time and labor in designing a nasal spray product to achieve desired product performance characteristics can be reduced.

Comparison of neurofuzzy logic and decision trees in discovering knowledge from experimental data of an immediate release tablet formulation.

Understanding of the cause-effect relationships between formulation ingredients, process conditions and product properties is essential for developing a quality product. However, the formulation knowledge is often hidden in experimental data and not easily interpretable. This study compares neurofuzzy logic and decision tree approaches in discovering hidden knowledge from an immediate release tablet formulation database relating formulation ingredients (silica aerogel, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and process variables (dwell time and compression force) to tablet properties (tensile strength, disintegration time, friability, capping and drug dissolution at various time intervals). Both approaches successfully generated useful knowledge in the form of either "if then" rules or decision trees. Although different strategies are employed by the two approaches in generating rules/trees, similar knowledge was discovered in most cases. However, as decision trees are not able to deal with continuous dependent variables, data discretisation procedures are generally required.