Molecular origin of mechano-sorptive creep in cellulosic fibres.

Mechano-sorptive creep, i.e. the increased rate of creep that occurs during changing relative humidity, when loading paper or wood, is a phenomenon still not fully understood. This phenomenon was here investigated by examining the changes occurring at the molecular level utilising FTIR spectroscopy. By subjecting the paper to deuterated water, the changes involving both the crystalline hydroxyls as well as those in accessible regions could be examined. During loading, the cellulose molecular chains are stretched taking the load. In addition, during mechano-sorptive creep a further exchange from OH to OD groups occurred. This was interpreted as caused by slippage between cellulose fibrils allowing previously non-accessible hydroxyls to become available for deuterium exchange. Thus, the loosening of the structure, during the changing moisture conditions, is interpreted as what has led to the increased creep and the possibility for new areas of cellulose fibril/fibril aggregates to be exposed to the deuterium exchange.

Synthesis, Comparison, and Optimization of a Humic Acid-Quat10 Polyelectrolyte Complex by Complexation-Precipitation versus Extrusion-Spheronization.

A novel humic acid and polyquaternium-10 polyelectrolyte complex (PEC) was synthesized utilizing two methods and the solubility and permeability of efavirenz (EFV) were established. Complexation-precipitation and extrusion-spheronization were used to synthesize and compare the drug-loaded PECs. The chemical integrity, thermo-mechanical differences, and morphology between the drug-loaded PECs produced by the two methods were assessed by attenuated total reflectance-Fourier transform infrared, differential scanning calorimetry, and SEM. The extent of drug solubilization was determined using the saturation solubility test while the biocompatibility of both PECs was confirmed by cytotoxicity studies on human adenocarcinoma cells (caco2). Bio-relevant media was used for the solubility and permeability analysis of the optimized PEC formulations for accurate assessment of formulation performance. Ritonavir (RTV) was loaded into the optimized formulation to further corroborate the impact of the PEC on the solubility and permeability properties of a poorly soluble and poorly permeable drug. The optimized EFV-loaded PEC and the RTV-loaded PEC exhibited 14.16 ± 2.81% and 4.39 ± 0.57% increase in solubility, respectively. Both PECs were compared to currently marketed formulations. Intestinal permeation results revealed an enhancement of 61.24 ± 6.92% for EFV and 38.78 ± 0.50% for RTV. Although both fabrication methods produced PECs that enhanced the solubility and permeability of the model Biopharmaceutics Classification System Class II and IV drugs, extrusion-spheronization was selected as most optimal based on the higher solubility and permeability improvement and the impact on caco2 cell viability.

The Solubility of Microcrystalline Cellulose in Sodium Hydroxide Solution Is Inconsistent with International Specifications.

Microcrystalline cellulose (MCC) is used globally as an inactive ingredient in food and nutraceutical products and is commonly used as a food additive. To confirm the conformity of MCC to the solubility requirements stipulated in international specifications, the solubilities of commercially available MCC products were tested in sodium hydroxide (NaOH) solution. All of the samples were insoluble in NaOH solution, which is inconsistent with the descriptions provided in international specifications. We also prepared celluloses with different degree of polymerization (DP) values by acid hydrolysis. Celluloses with lower DP were prepared using a three-step process, and their solubilities were tested in NaOH solution. These celluloses were found to be insoluble, which is inconsistent with the descriptions provided in international specifications. The present study suggests that the descriptions of the solubility of the celluloses in NaOH solution found in the current international specifications should be revised.

Application of Multivariate Strategies to the Classification of Pharmaceutical Excipient Manufacturers Based on Near-Infrared (NIR) Spectra.

Using partial least square discriminate analysis (PLSDA), we studied the spectroscopic differences between the commonly used filler-binder microcrystalline cellulose (MCC) from five manufactures. These samples had subtle differences in the chemical and physical properties, which are often the cause of differences in excipient performance. Studying these differences allowed us to build and validate a model to classify five manufacturers of MCC using near-infrared (NIR) spectra. The sample training set includes 39 MCC samples collected from five manufactures with regions spanning the United States of America, Japan, Taiwan, Germany, and Brazil. The samples from individual manufacturers include diverse grades that differ in moisture content, particle size, and bulk density. Optimized pretreatment methods were identified as standard normal variate normalization, followed by Savitzky-Golay second derivative, mean centering, and orthogonal signal correction. The model was optimized with cross-validation and validated with an independent sample set comprising nine samples collected from those five manufacturers. The results showed that none of the samples in the independent validation set was misclassified. The score and loading plots revealed that the differences in content of oxidized cellulose group, water content and states, hydrogen bonding, and degree of polymerization of the MCC samples are responsible for the class differentiation. Permutation test demonstrated that the outcome of the PLSDA model was significantly different from that of the randomly generated model. The advantages and limitations of the method in this type of application were discussed.

The effect of capsule-filling machine vibrations on average fill weight.

The aim of this paper is to study the effect of the speed of capsule filling and the inherent machine vibrations on fill weight for a dosator-nozzle machine. The results show that increasing speed of capsule filling amplifies the vibration intensity (as measured by Laser Doppler vibrometer) of the machine frame, which leads to powder densification. The mass of the powder (fill weight) collected via the nozzle is significantly larger at a higher capsule filling speed. Therefore, there is a correlation between powder densification under more intense vibrations and larger fill weights. Quality-by Design of powder based products should evaluate the effect of environmental vibrations on material attributes, which in turn may affect product quality.

3D simulation of internal tablet strength during tableting.

This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle-particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and experimental compression forces increased similarly. Tablet-breaking forces increased with the calculated strengths obtained from the simulations. The calculated bond strength distribution inside the tablets showed features similar to those of the density and pressure distributions in the literature. However, the bond strength distributions at the center of the tablets varied considerably between individual tablets.

A kinetic study of the polymorphic transformation of nimodipine and indomethacin during high shear granulation.

The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol(-1) from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.

Rapid particle size measurement using 3D surface imaging.

The present study introduces a new three-dimensional (3D) surface image analysis technique in which white light illumination from different incident angles is used to create 3D surfaces with a photometric approach. The three-dimensional features of the surface images created are then used in the characterization of particle size distributions of granules. This surface image analysis method is compared to sieve analysis and a particle sizing method based on spatial filtering technique with nearly 30 granule batches. The aim is also to evaluate the technique in flowability screening of granular materials. Overall, the new 3D imaging approach allows a rapid analysis of large amounts of sample and gives valuable visual information on the granule surfaces in terms of surface roughness and particle shape.

Development of controlled-release matrix tablet of risperidone: influence of Methocel®- and Ethocel®-based novel polymeric blend on in vitro drug release and bioavailability.

Controlled-release (CR) matrix tablet of 4 mg risperidone was developed using flow bound dry granulation-slugging method to improve its safety profile and compliance. Model formulations F1, F2, and F3, consisting of distinct blends of Methocel® K100 LV-CR and Ethocel® standard 7FP premium, were slugged. Each batch of granules (250-1,000 µm), obtained by crushing the slugs, was divided into three portions after lubrication and then compressed to 9-, 12-, and 15-kg hard tablets. In vitro drug release studies were carried out in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using a paddle dissolution apparatus run at 50 rpm. The CR test tablet, containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness, exhibited pH-independent zero-order release kinetics for 24 h. The drug release rate was inversely proportional to the content of Ethocel®, while the gel layer formed of Methocel® helped in maintaining the integrity of the matrix. Changes in the hardness of tablet did not affect the release kinetics. The tablets were reproducible and stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. Risperidone and its active metabolite, 9-hydroxyrisperidone, present in the pooled rabbit's serum, were analyzed with HPLC-UV at λ(max) 280 nm. The CR test tablet exhibited bioequivalence to reference conventional tablet in addition to the significantly (p < 0.05) optimized peak concentration, C(max), and extended peak time, T (max), of the active moiety. There was a good association between drug absorption in vivo and drug release in vitro (R(2) = 0.7293). The successfully developed CR test tablet may be used for better therapeutic outcomes of risperidone.

Correlating patient-reported response to hydroxypropyl cellulose ophthalmic insert (LACRISERT®) therapy with clinical outcomes: tools for predicting response.

BACKGROUND/AIMS: To determine whether patient-reported improvement in symptoms of dry eye syndrome, activities of daily living, and other quality-of-life measures after treatment with hydroxypropyl cellulose ophthalmic inserts correlates significantly with physician assessment of clinical outcomes. METHODS: Patient registry of those treated for 1 month with inserts as monotherapy or in combination with existing treatments for moderate-to-severe dry eye syndrome. A total of 520 participants were enrolled. Of those, 418 patients completed the study. Results of this registry were evaluated and correlations were calculated to determine whether patient-reported symptoms, quality of life, and changes in disease severity based on the Ocular Surface Disease Index, and activities of daily living outcomes are predictive of physician assessment of clinical signs, symptoms, and adherence to therapy. RESULTS: Most patients reported overall improvement in their condition. Patient-reported improvements in the symptoms of dry eye syndrome and activities of daily living were significant predictors of physician assessment of compliance with insert therapy, improvement in symptoms and clinical signs, effectiveness of therapy, and acceptance of use as adjunctive therapy. CONCLUSIONS: Patient-reported symptoms and activities of daily living are predictors of patient compliance and treatment success with the use of inserts, as reported by treating physicians. The benefits were additive to the standard of care that was continued during the course of the study. These predictors, along with clinical diagnostic tests, can be used by eye care professionals to assess the efficacy of treatment for moderate-to-severe dry eye syndrome quickly and reliably.

Platelet activation during haemodialysis: comparison of cuprammonium rayon and polysulfone membranes.

BACKGROUND/AIM: Haemodialysis-treated patients are at a high risk of developing cardiovascular disease. Part of this risk may be attributable to the type of the dialysis membrane used. We evaluated whether different dialysis membranes differ with respect to platelet activation. METHODS: In a randomized crossover trial, the platelet activation was measured in 14 patients treated with two different dialyzers (cuprammonium rayon membrane and polysulfone membrane). We compared the platelet activation over the dialyzer and between dialyzers after several weeks of dialysis. RESULTS: There were no differences between the two dialyzers in platelet activation over the dialyzer. After 2 weeks, however, the expression of CD62P, CD63, and PAC-1 was statistically significantly lower after cuprammonium membrane treatment than after polysulfone membrane treatment (mean fluorescence intensity in arbitrary units 8.0 vs. 11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). CONCLUSION: Dialysis with a polysulfone membrane seems to lead to more platelet activation than dialysis with a cuprammonium membrane.

Conventional blood sampling versus On-Line Clearance Monitoring.

On-line Clearance Monitoring (OCM) calculates the Kt/V during a dialysis session using a module incorporated into the Fresenius 4008 H/S haemodialysis machine (1). The method is based on repeated increments in dialysate sodium concentrations followed by measuring the change of dialysate sodium concentration after the dialysate has passed through the kidney. OCM is a patient friendly, non-invasive and easy method for measuring Kt/V. Kt/V calculated on single-pool urea kinetics according to Daugirdas was compared to Kt/V measured by OCM in thirty stable patients on chronic haemodialysis. Patients were dialysed using a dialyser with either a high-flux polysulfone or a haemophane membrane. In four patients OCM was measured in ten consecutive sessions to assess the intra-individual variation in OCM. The calculated Kt/V was compared to Kt/Vocm in three patients at five consecutive dialysis sessions to measure the intra-individual correlation. A linear correlation was present between Kt/Vocal and Kt/Vac for both the polysulfone and haemophane membrane. Intra-individual Kt/Vocm showed very stable values with an average variation of less than 5%. Intra-individual correlation between calculated Kt/V and Kt/Vocm was high.

[Re-evaluation of an embolic material for aneurysm cellulose acetate polymer].

OBJECTIVE: To re-evaluate the safety, effect, and pathological reactions of cellulose acetate polymer (CAP). METHODS: 30 right carotid arteries of rats were embolized and got two embolized vessels for histological study in each of the seven stages within four months. Fifteen canine aneurysmal models were created by transplantation of venous pouches. Twelve of them were occluded with CAP. Digital Subtraction Angiography (DSA) follow-ups of occluded aneurysmal models were carried out 1, 2 and 8 weeks after occlusion. One animal was sacrificed randomly at each stage for pathological study. RESULTS: Only five of the 12 aneurysmal models were completely or partially occluded within the patency of parent arteries within two months of observation after embolization with CAP. Stenosis of one branch of aneurysmal parent artery was occurred. The residual cavity of one partially occluded model artery was enlarged. Two models ruptured on four and five days after embolization. Three embolized models and their parent arteries were all occluded. PATHOLOGICAL FINDINGS: acute pathological reaction occurred within vessels embolized with CAP. Endothelial cell and basal membrane were damaged and vanished. Elastic lamina was exposed to arterial lumen and attached by thrombus layer. Fibrous cells and smooth muscle cells showed obvious degeneration. CAP and thrombus were gradually organized in two months after thrombosis. The orifices of aneurysmal models were covered with newly developed fibrous tissue and endothelial cells in two months after thrombosis. CONCLUSIONS: We think that acute chemical erosive effect of CAP was evident. A strong effect could lead to rupture of some of the CAP thrombosed aneurysmal models. Besides, stenosis or occlusion of the parent arteries could be induced in some cases after embolization with CAP. For the above shortcomings and limitations, it should be improved carefully before it is applied in clinic.

[Life-cycle assessment of single-use versus reusable surgical drapes (cellulose/polyethylene-mixed cotton system)]. / Einweg- versus Mehrweg-Patientenabdeckung im Operationssaal. Okobilanz: Vergleich von Zellstoff-Polyethylen- und Baumwoll-Mischabdeckung.

Surgical drapes made of cotton are under increasing competition with various disposable products and reusable draping systems (e.g., made of synthetic fabrics like polyester). When making a choice to use one of these medical devices in practical surgery, major aspects like handling, hygienic safety and costs, but also environmental effects have to be taken into account. In this study a mixed system for patient drapes (reusable cotton drapes combined with a reduced set of impermeable single-use drapes made of cellulose/polyethylene) was compared to a system that is only based on single-use drapes with regard to ecology [life-cycle assessment (LCA)]. The medical literature was reviewed to assess important medical aspects of the use of patient drapes, resulting in the statement that there are no conclusive arguments to support a clear hygienic superiority of one of these alternatives. Based on the conditions assumed and stated, the results of the LCA indicate that the mixed draping system is associated with two times more total energy consumption. In addition, more water is needed and more CO2 emissions are produced. However, draping with the single-use product results in more clinical waste. Regarding water pollution no system proved superior. It is difficult to compare and weigh various environmental aspects like the polluting cultivation of cotton in distant countries (reusable drapes) and the higher figure of transportation necessary to deliver the single-use product within Germany. It is an important disadvantage of the mixed system that it combines the ecological burden of both cotton drapes and the single-use alternative.

Spent cellulose casings as potential feed ingredients for ruminants.

Cellulose casings are used to contain and form meat and poultry emulsions during the smoking and cooking process. Casings then are stripped from the cooked product and traditionally disposed of in landfills. Because of the bulk of the spent cellulose casings (SCC), rapid composting technology may be used to reduce bulkiness. The following SCC were evaluated in vitro and in vivo: fibrous ground (FG), fibrous composted (FC), NOJAX ground (NG), and NOJAX composted (NC). In vitro digestibility was determined by incubating SCC with mixed ruminal bacteria for 0, 6, 12, 24, 36, 48, and 72 h. In vivo data were collected using four ruminally cannulated Holstein steers in a 4 x 4 Latin square design. Diets consisted of a 50:50 ratio of alfalfa hay-wheat middlings with 5% cornsteep liquor. Diets contained no SCC (CON) or 25% (DM basis) of the FC, FG, or NC SCC substrate. Casings were high in structural carbohydrate and salt content but low in CP, ether extract, and lignin concentrations. In vitro OM digestibility at 24 h was highest (P < .05) for FC and lowest (P < .05) for NG; FG and NC were intermediate. Composting tended to reduce fiber content and increase digestion. In vivo intakes and digestibilities were not adversely affected by inclusion of SCC in the diet. Thus, SCC have the ability to partially replace more traditional forages, such as alfalfa hay and wheat middlings, in high-fiber diets for growing beef cattle. Limitations in the use of SCC as a partial replacement of traditional feedstuffs will likely be because of high salt concentrations in the casings resulting from product brine chilling.

Specific IgE determination using the CAP system: comparative evaluation with RAST.

The CAP system's main contribution is its solid phase, which consists of a cellulose polymer activated within a capsule (the ImmunoCAP). This solid phase can bind more protein to it, and, in addition, the conditions of reaction seem to make the system more sensitive at detecting antibodies to certain antigens. It is therefore important to assess the new analytical and diagnostic performance in comparison with previous systems. In this context, we studied the reliability and comparison with the RAST and with skin tests carried out on 144 pediatric patients. Skin tests and specific IgE for radioimmunological RAST (radio-allergosorbent test) and for the fluoroimmunological CAP system were performed on all the patients. The RAST/CAP correlation quotients for the different allergens tested varied between 0.971 and 0.991. Diagnostic sensitivity increased for all the allergens studied and specificity remained unchanged. The system provides reliable results, with better diagnostic capacity than RAST, but it must be quantified for each allergen because its results are not interchangeable.

Variations in corneal curvature and refractive error in CAB gas-permeable contact lens wearers.

34 patients wearing CAB gas-permeable contact lenses were studied during a 360-day period. It was found that the horizontal corneal meridian and the spherical refractive error did not show change. However, a significant decrease was observed in both with-the-rule toricity and with-the-rule astigmatism.

Biological evaluation of biomaterials for cardiovascular applications: some current results.

The proper biologic evaluation of biomaterials for blood-contacting applications must include considerations of hemorheologic parameters, species-related differences, and damages to the reticuloendothelial system. Although there are no materials currently available that are completely blood compatible, several smooth-surfaced polymers are quite tolerable in the physiological environment. These include chemically grafted polyacrylamide hydrogels, glow-discharge polymers of silica-free hexamethldisiloxane, and ethyl cellulose perfluorobutyrate.