Carboxymethyl mungbean starch as a new pharmaceutical gelling agent for topical preparation

An application of carboxymethyl mungbean starch (CMMS) as a gelling agent in the topical pharmaceutical preparation was investigated. CMMS was prepared using specific conditions that yielded a high-viscosity product. Polymer gels and gel bases were prepared at 1-10% (wt/wt), and physicochemical studies were carried out in comparison with four standard gelling agents: carbopol 940 (CP), hydroxypropylmethyl cellulose (HPMC), methyl cellulose (MC), and sodium carboxymethyl cellulose (SCMC). Piroxicam was used as a model drug to study the drug release profile of the gel formulations. The tackless, greaseless, and transparent CMMS gels exhibited pseudoplastic behavior with thixotropy at concentrations less than 5% (wt/wt). At a concentration of 5% (wt/wt) and higher, the semisolid gels showed plastic flow characteristics. Viscosity and X-ray diffraction results indicated a good compatibility between CMMS and the acidic piroxicam. No precipitation of piroxicam or phase separation was observed during a stability test. The release rate of piroxicam from 3% (wt/wt) CMMS gel was 1,003.79 +/- 105.08 microg/cm(2), which was comparable with 947.66 +/- 133.70 microg/cm(2) obtained from a 0.5% (wt/wt) carbopol formulation. The release profiles of both formulations were consistent and remained unchanged after 2 months' storage. Viscosity played an important role in controlling the release rate of low concentration CMMS formulations by regulating the drug diffusion. At a concentration of 5% (wt/wt) CMMS and higher, the release rates of piroxicam were not significantly different. A plausible explanation based on the nature of the gelling agent was proposed. Stability and drug release profiles of CMMS and commercial gelling agents were compared. The results supported the potential use of CMMS as a new, effective gelling agent for topical gel preparation.     

Exploring the importance of the relative solubility of matrix and analyte in MALDI sample preparation using HPLC

New insight into the role of solubility in the sample preparation process for MALDI MS is reported. Reversed-phase gradient HPLC conditions were developed that enable the analysis of a broad range of analyte polarities with a single method. This HPLC method was used to establish a relative polarity scale for a series of 15 MALDI matrix materials, a set of example peptides, and a series of model polymer materials with a broad range of polarity. Examples of each polymer type within the range of 6000-10,000 were analyzed with six matrixes that cover a broad range of polarity using MALDI TOFMS. With regard to polymer signal-to-noise ratio, the matrix and polymer combinations that had a close match of HPLC retention time produced the best MALDI spectra. Conversely, the matrix and polymer combinations that have a large difference in HPLC retention time produced poor MALDI spectra. The results suggest that there is a relationship between polarity (solubility) and effective MALDI sample preparation. The relative HPLC retention time of an unknown polymer can serve as a starting point for predicting the matrix (or range of matrixes) that would be most effective.     

Comparison of linear and non-linear monotonicity-based shape reconstruction using exact matrix characterizations

Detecting inhomogeneities in the electrical conductivity is a special case of the inverse problem in electrical impedance tomography, that leads to fast direct reconstruction methods. One such method can, under reasonable assumptions, exactly characterize the inhomogeneities based on monotonicity properties of either the Neumann-to-Dirichlet map (non-linear) or its Fréchet derivative (linear). We give a comparison of the non-linear and linear approach in the presence of measurement noise, and show numerically that the two methods give essentially the same reconstruction in the unit disk domain. For a fair comparison, exact matrix characterizations are used when probing the monotonicity relations to avoid errors from numerical solution to PDEs and numerical integration. Using a special factorization of the Neumann-to-Dirichlet map also makes the non-linear method as fast as the linear method in the unit disk geometry.     

Immunochemical approaches for purification and detection of TNT traces by antibodies entrapped in a sol-gel matrix

A highly sensitive immunochemical method for immunoaffinity purification (IAP) and detection of trace amounts of TNT was developed on the basis of antibodies (Abs) in a ceramic matrix (sol-gel). The study resulted in: (i) a highly sensitive and reproducible TNT ELISA (I50 and I20 values of 0.4 +/- 0.09 ppb and 0.12 +/- 0.03 ppb, respectively; n = 12), which is highly specific to TNT; and (ii) successful entrapment of the Abs that bound free analyte from solution. Binding was found to be highly reproducible, dose dependent, and only slightly (1.2-1.8-fold) lower than that in solution. The entrapped Abs did not leach from the matrix and were tolerant of absolute ethanol, acetone, and acetonitrile. Bound analytes could be easily eluted from the sol-gel matrix at high recoveries. The sol-gel-based IAP method described above introduces a simple one-step procedure that has a high potential to serve as a suitable and convenient immunochromatographic device for cleanup and concentration of TNT from "real field" samples in a manner that complies with both chemical and immunochemical residue analysis methods.     

Deciphering the expression dynamics of ANGPTL8 associated regulatory network in insulin resistance using formal modelling approaches

ANGPTL8 is a recently identified novel hormone which regulates both glucose and lipid metabolism. The increase in ANGPTL8 during compensatory insulin resistance has been recently reported to improve glucose tolerance and a part of cytoprotective metabolic circuit. However, the exact signalling entities and dynamics involved in this process have remained elusive. Therefore, the current study was conducted with a specific aim to model the regulation of ANGPTL8 with emphasis on its role in improving glucose tolerance during insulin resistance. The main contribution of this study is the construction of a discrete model (based on kinetic logic of René Thomas) and its equivalent Stochastic Petri Net model of ANGPTL8 associated Biological Regulatory Network (BRN) which can predict its dynamic behaviours. The predicted results of these models are in‐line with the previous experimental observations and provide comprehensive insights into the signalling dynamics of ANGPTL8 associated BRN. The authors’ results support the hypothesis that ANGPTL8 plays an important role in supplementing the insulin signalling pathway during insulin resistance and its loss can aggravate the pathogenic process by quickly leading towards Diabetes Mellitus. The results of this study have potential therapeutic implications for treatment of Diabetes Mellitus and are suggestive of its potential as a glucose‐lowering agent.Inspec keywords: molecular biophysics, biomembranes, diseases, stochastic processes, biochemistry, patient treatment, Petri nets, genetics, sugar, cellular biophysics, biology computingOther keywords: ANGPTL8 associated regulatory network, formal modelling approaches, lipid metabolism, compensatory insulin resistance, glucose tolerance, equivalent Stochastic Petri Net model, ANGPTL8 associated BRN     

Comparative study of different approaches for preparation of chlorzoxazone orodispersible tablets

Abstract

Context: Muscle spasm is a painful involuntary contraction of muscles, which causes involuntary movement and distortion. Chlorzoxazone is a centrally acting muscle-relaxant with sedative properties, but given orally, it is hepatically metabolized leading to decreased bioavailability.

Objective: Orodispersible tablets (ODTs) of chlorzoxazone were formulated using two different approaches; by coprocessed excipients (CE) or by liquisolid (LS) technique.

Materials and methods: Pharmaburst^® 500, Starlac^®, Pearlitol flash^®, Prosolv^® odt and F-melt^® were used as coprocessed superdisintegrants, whereas in LS, Avicel^® PH101, Microcelac^® 100 and Cellactose^® 80 were used as carriers, while Aerosil^® 200 was the coating material. ODTs were evaluated in terms of weight and thickness variations, drug content, hardness, friability, wetting time, dissolution, disintegration time (DT) and palatability.

Results: In vitro DT of CE-ODTs ranged from 26.43?±?1.693?s to >180?s, whereas it was between 25.42±?0.203?s to >180?s in LS-ODTs. Complete drug release within 15?min was attained by CE1 prepared with 92.5?mg Pharmaburst^® 500. In vivo DT of CE1 and LS3 were 19.779?±?0.810 and 18.105?±?0.423?s, respectively, using six volunteers. Volunteers found that CE1 had more acceptable taste and was more palatable than LS3.

Conclusion: It was concluded that chlorzoxazone ODTs could be successfully formulated using either CE or LS techniques and be used as novel dosage forms for pediatrics and geriatrics showing improved drug release. Moreover, CE technique was superior to LS technique in terms of palatability.     

Comparison of stochastic parametrization approaches in a single-column model

We discuss and test the potential usefulness of single-column models (SCMs) for the testing of stochastic physics schemes that have been proposed for use in general circulation models (GCMs). We argue that although single-column tests cannot be definitive in exposing the full behaviour of a stochastic method in the full GCM, and although there are differences between SCM testing of deterministic and stochastic methods, SCM testing remains a useful tool. It is necessary to consider an ensemble of SCM runs produced by the stochastic method. These can be usefully compared with deterministic ensembles describing initial condition uncertainty and also with combinations of these (with structural model changes) into poor man's ensembles. The proposed methodology is demonstrated using an SCM experiment recently developed by the GCSS (GEWEX Cloud System Study) community, simulating transitions between active and suppressed periods of tropical convection.     

Experimental results for improving the matrix condition using a hybrid optical system

We present preliminary experimental results for implementing the "blurred trajectories" method on three parallel optics (PO) systems. The "main" system and "auxiliary" optics were simple laboratory graded lenses attached to an iris diaphragm. When applying the blurred trajectories method we first show an improvement in the matrix condition, as the matrix condition number decreased in a range of factors of 3 to 418 relative to the main system. Following that, image restoration by weak regularization was performed so that the system matrix condition dominated the restoration process. It was shown that the restoration results of the PO are better than those of the main system and the auxiliary optics separately. In addition, the quality of the restoration follows the system's matrix condition. The improvement in the matrix condition achieved by the PO system improved the immunity to detection noise. Finally, a comparison to Wiener filtering restoration shows that it is also generally inferior to the proposed method.     

Influence of cation-adsorption and sonochemical approaches on the preparation of gold catalyst

Nanosize mesoporous ZrO2 support was synthesized via a solid-state reaction route. A new preparation method involving cation-adsorption and sono-chemical procedure was developed for mesoporous ZrO2 supported nano-gold catalyst.     

Quantification of human error in maintenance using graph theory and matrix approach

Assessment of human error in maintenance requires identification of the contributing factors that lead to human error(s). These factors are called human error inducing factors (HEIFs), which take into consideration both the active and latent error contributing aspects related to man, machine and environment. A systems approach of the Graph Theory is applied in this paper for quantifying human error in maintenance activities that models the identified factors and their interactions/interrelationships in terms of human error digraph. The nodes in the digraph represent the HEIFs and the edges represent their interrelationships. The digraph is converted into an equivalent matrix and an expression based on this is developed, which is characteristic of the human error in maintenance. This expression is used to evaluate a human error index by substituting the numerical value of the factors and their interrelations. The index is a measure of the human error potential involved in the maintenance of systems. A higher value of index indicates that the error likelihood is more for the associated tasks, and more efforts are required to make the system less prone to human error. The proposed methodology is illustrated using a case study. The approach is anticipated to play a significant role in identifying sources of human errors and predicting their impact; and will help to integrate human factors during design stage with the objective of reducing human error in maintenance. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparison of three pharmaceutical products obtained from Mexico and the United States: a case study

In recent years, there has been much debate concerning the relative pros and cons of purchasing medications from foreign markets such as Mexico and Canada. The following study compares the content uniformity and weight variation for three medicinal products, acquired from pharmacies in both Mexico and the United States: amoxicillin capsules (500 mg), amoxicillin/clavulanic acid suspension (400 mg and 57 mg/5 mL, respectively), and furosemide tablets (40 mg). Twenty capsules/tablets were individually weighed and a designated aliquot was taken. Following dissolution in an appropriate solvent and sonication, a sample was taken and analyzed via high performance liquid chromatography (HPLC). The suspensions were prepared according to directions on the label. Five samples of the suspensions were then taken and analyzed via an appropriate HPLC method. The content uniformity for the amoxicillin capsules was found to be 15.4 ± 2.4% and 99.4 ± 9.3%, for Mexican and U.S. capsules, respectively. The percent relative standard deviation (% RSD) for weight variation was found to be 8.7% and 1.5% for capsules obtained from Mexico and the United States, respectively. Content uniformity analysis for the Mexican suspension product resulted in an average of 85.5 ± 1.2% for amoxicillin and 98.6 ± 1.9% for the clavulanic acid content, while the results for the U.S. suspension product were 104.4 ± 3.1% and 117.8 ± 3.6% for amoxicillin and clavulanic acid, respectively. Content uniformity for the furosemide tablets was found to be 90.3 ± 4.8% and 95.6 ± 2.1% for Mexican and U.S. tablets, respectively. The % RSD of weight variation for the Mexican tablets was 2.1%, while the % RSD for the U.S. tablets was found to be 1.0%. From the three products tested, content analysis revealed that the amount of active ingredients for two of the products acquired in Mexico were appreciably less than the concentrations for their U.S. counterparts.     

Development of a simple and practical method for estimating the liquid absorption of pharmaceutical porous materials using a capillary rise technique

Porous materials are attractive substances for designing pharmaceutical particulates. However, understanding the behavior of liquid absorption into the intra-pores and interstices of porous carrier particles is important to effectively manufacture active pharmaceutical ingredients (APIs) using these carriers. In this study, we established a simple and practical method for evaluating the liquid absorption behavior of porous carriers using force tensiometry and a capillary rise technique. Different-sized tablets of porous materials were prepared and evaluated by this method using various solvents to estimate liquid absorption into the intra-particle pores and interstices of the particles. The amount of liquid trapped in the interstices of the particles decreased with decreasing tablet volume, after which the amount of liquid in the intra-particle pores could be estimated. Finally, API-loaded particles were prepared by absorbing the API solution into porous carriers based on the intra-capacity revealed above. No free API was found on the surface of the prepared particles, as it was well absorbed into the intra-particle pores. Collectively, this tensiometer method using different-sized tablets of porous materials appears to be a promising technique for evaluating the liquid absorption characteristics of porous pharmaceutical materials.     

Comparison of different approaches for estimation of creep crack initiation

In large components such as rotors defects due to manufacturing processes have to be taken into account and crack assessments based on findings of non-destructive evaluation are necessary. Approaches are used in remaining life estimations, for example:

• Time Dependent Failure Assessment Diagram (TDFAD),

• Two Criteria Diagram (2CD) and

• Nikbin–Smith–Webster-Model (NSW-Model).

The TDFAD approach is currently being developed within the R5 procedures as an alternative to conventional methods for predicting incubation and the early stages of Creep Crack growth. A key requirement of TDFAD approaches is the evaluation of a time dependent creep toughness, denoted K_c mat. The 2CD approach has been developed independently in Germany to assess Creep crack incubation in ferritic steels. This approach uses crack tip and ligament damage parameters, R_K and R_σ, respectively. Furthermore the NSW-Model is employed for the estimation of creep crack initiation by using the creep fracture mechanics parameter C^*. Calculations and used parameters were compared for a ferritic 1CrMoV-steel.     

Comparison of dose estimation from occupational exposure to 239Pu using different modelling approaches

Several approaches are available for bioassay interpretation when assigning Pu doses to Mayak workers. First, a conventional approach is to apply ICRP models per se. An alternative method involves individualised fitting of bioassay data using Bayesian statistical methods. A third approach is to develop an independent dosimetry system for Mayak workers by adapting ICRP models using a dataset of available bioassay measurements for this population. Thus, a dataset of 42 former Mayak workers, who died of non-radiation effects, with both urine bioassay and post-mortem tissue data was used to test these three approaches. All three approaches proved to be adequate for bioassay and tissue interpretation, and thus for Pu dose reconstruction purposes. However, large discrepancies are observed in the resulting quantitative dose estimates. These discrepancies can, in large part, be explained by differences in the interpretation of Pu behaviour in the lungs in the context of ICRP lung model. Thus, a careful validation of Pu lung dosimetry model is needed in Mayak worker dosimetry systems.     

One-step preparation of FeCo nanoparticles in a SBA-16 matrix as catalysts for carbon nanotubes growth

Nanocomposites containing FeCo alloy nanoparticles dispersed in a highly ordered 3D cubic Im3m mesoporous silica (SBA-16) matrix were prepared by a novel, single-step templated-assisted sol-gel technique. Two different approaches were used in the synthesis of nanocomposites; a pure SBA-16 sample was also prepared for comparison. Low-angle X-ray diffraction, transmission electron microscopy and N2 physisorption at 77 K show that after metal loading, calcination at 500 degrees C and reduction in H2 flux at 800 degrees C the nanocomposites retain the cubic mesoporous structure with pore size not very different from the pure matrix. X-ray absorption fine structure (EXAFS) analysis at Fe and Co K-edges demonstrates that the FeCo nanoparticles have the typical bcc structure. The final nanocomposites were tested as catalysts for the production of carbon nanotubes by catalytic chemical vapour deposition and high-resolution TEM shows that good quality multi-walled carbon nanotubes are obtained.     

Quantitative determination of acetaminophen in pharmaceutical formulations using differential scanning calorimetry. Comparison with spectrophotometric method

In this paper our previous researches dealing with compatibility, thermoanalytical characterization, the kinetics of thermal degradation of acetaminophen, either pure or contained in some commercial pharmaceutical formulations, have found applications outlets. In a previous investigation the possible interactions between acetaminophen and four excipients contained in the commercial pharmaceutical formulations were tested. As a continuation of this research in the present study an analytical method based on differential scanning calorimetry (DSC) was applied to determine the acetaminophen content of four commercial pharmaceutical formulations. For a fifth drug it was shown that the method is not applicable owing to observed incompatibility with one of the excipients. Finally, the analytical results obtained were compared with those derived from two UV spectrophotometric methods (one, i.e., “direct method,” recommended by the Pharmacopeia and the other based on the first-order derivative UV spectra).     

Monitoring of a pharmaceutical nanomilling process using grating light reflection spectroscopy

An optical diagnostic method, grating light reflection spectroscopy (GLRS), has been demonstrated for the in situ monitoring of properties of heterogeneous matrices in industrial processes. The technique is based on measurements near the critical points of intensity and phase in waves reflected from a transmission diffraction grating in contact with a diagnostic sample. The features contained in the reflection spectrum near these thresholds allow for the simultaneous determination of the real and imaginary parts of the dielectric function of the sample. Using these data, the milling progress of highly concentrated fluid suspensions is observed as the material is milled from approximately 40 mm to 160 nm in diameter. A theoretical model that closely resembles experimentally determined spectra was constructed and applied in combination with principal components analysis (PCA) to demonstrate that GLRS can be used to closely monitor changes in the mean particle size of the nanomilled drug product.     

Polarization and retinal image quality estimates in the human eye

We have previously studied how polarization affects the double-pass estimates of the retinal image quality by using an imaging polarimeter [Opt. Lett. 24, 64 (1999)]. A series of 16 images for independent combinations of polarization states in the polarimeter were recorded to obtain the spatially resolved Mueller matrices of the eye. From these matrices, double-pass images of a point source for light with different combinations of incoming (first-pass) and outcoming (second-pass) polarization states were reconstructed and their corresponding modulation transfer functions were calculated. We found that the retinal image or, alternatively, the ocular aberrations, are nearly independent of the state of polarization of the incident light (in the first pass). This means that a significant improvement in the ocular optics by using a specific type of polarized light could not be achieved. However, quite different estimates of the retinal image quality are obtained for combinations of polarization states in both the first and the second passes in the double-pass apparatus.