Preparation, Physical Characterization, Mechanisms of Drug/Polymer Interactions, and Stability Studies of Controlled-Release Solid Dispersion Granules Containing Weak Base as Active Substance

Verapamil hydrochloride solid dispersion granules were prepared using solvent evaporation technique. Ethyl cellulose, hydroxypropyl cellulose, Eudragit L or Eudragit S were used as polymers for controlling the dissolution rate of the drug substance, and to avoid the continuous decrease of drug dissolution rate at higher pH values. By incorporating Eudragit L in ethyl cellulose network it is possible to prepare controlled-release formulation with increased release rate of active substance (weak base) at higher pH values without causing abrupt drug release at lower pH values. The release rate at low pH values was not highly influenced by Eudragit L content. The behavior of Eudragit L and Eudragit S in coprecipitates was different relating to the solubilization effect and the release of active substance. In order to understand the drug release mechanism better, the release data were tested assuming Higuchi model and first-order kinetic model. Since the calculated correlation coeflcients were very close for both kinetics, to distinguish between the mechanisms the differential forms of first-order and square root of time equation were used. The differential test showed that diffusion-controlled release was operative in solid dispersions, except for series with higher content of Eudragit S. X-ray powder difSraction method, IR spectroscopy studies, and differential thermal analysis were used for physical characterization of coprecipitates and drugpolymer interaction evaluation. After 24 months of real time stability studies, the prepared coprecipitates were still x-ray amorphous, with no changes in their IR spectra and DTA studies. Ehe dissolution rates of the tested formulations showed no significant changes during the stability studies, reflecting the stability of x-ray amorphous drug phase.     

Interstitial Oxygen in Tin-Doped Indium Oxide Transparent Conductors

We report first-principles density functional theory calculations of interstitial oxygen in tin-doped indium oxide (ITO), a transparent conducting oxide. Interstitial oxygen plays a critical role in the defect of ITO because it is by removal of interstitial oxygen that n -type charge carriers are produced. The Frank and Köstlin defect model successfully rationalizes the observed conductivity, Sn-doping, and oxygen partial pressure dependencies of ITO by postulating that tin atoms, which substitute for indium, are clustered with interstitial oxygen. Structural evidence for such a clustering, however, remains ambiguous. Recently published Rietveld refinement results of X-ray and neutron diffraction data found interstitial oxygen to be significantly displaced (0.4 Å) from the ideal fourfold position. Our calculations show that the experimental position is plausible only if interstitial oxygen is clustered with Sn_In defects at any of the three d -type cation sites nearest to the interstitial, thereby providing direct structural confirmation of the Frank and Köstlin defect model.     

Improvements in data reduction in direct pulse heating calorimetry

This paper describes improvements introduced in data reduction in direct heating pulse specific heat experiments. In calculations of specific heat, it is necessary to calculate the first derivative of the recorded temperature data as a function of time. The error induced by different numerical differentiation techniques can represent a significant part of the overall measurement error. Thus, different digital filtering techniques, differentiation, and smoothing algorithms were applied and tested to examine their influence on the minimization of errors induced by noise, which is unavoidable in measured signals. A minimum square error criterion was applied in designing digital filters, with arbitrary prescribed magnitude characteristics. Attention was paid to applications when one or more structural phase transitions in the specimen material occur within the temperature range covered by the experiment. The cases where the frequency spectrum of induced noise overlaps with the spectrum of temperature transient signals originating from phase transitions were analyzed in detail. The effectiveness of the methods of extracting the final specific heat data from a noisy signal using different digital filtering techniques is demonstrated.Paper presented at the Fourth International Workshop on Subsecond Thermophysics, June 27–29, 1995, Köln, Germany.     

Nanoscale Magnetic Behavior of C60 Thin Films in Earth Magnetic Field under Polarization Light Influences

Magnetic behavior of C₆₀ thin films in the Earth's magnetic field under polarization light influence is presented. Transformation of magnetic field for two fullerene thin films of different thickness is investigated. Two proton magnetometers were used for these measurements. Samples of 30 nm and 250 nm thickness illustrate a significant change of magnetic field intensity under the influence of polarization light, in range from 3.4 to 12.9 nT, for 200 measurement data per sample.     

A Biopsychosocial Model of Disordered Eating and the Pursuit of Muscularity in Adolescent Boys.

This review provides an evaluation of the correlates and/or risk factors associated with disordered eating and the pursuit of muscularity among adolescent boys. One of the main conclusions is that similar factors and processes are associated with both behavioral problems. Several factors found to be consistently associated with disordered eating among boys are also similar to those found with girls. These include body mass index, negative affect, self-esteem, perfectionism, drug use, perceived pressure to lose weight from parents and peers, and participation in sports that focus on leanness. However, as many of the findings have only been verified using cross-sectional designs, prospective studies are now needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morphological Study of Products Containing β-Cyclodextrin

β-Cyclodextrin (β-CD) has been applied in various fields of drug formulation. Its presence in powder Paracetamol (PAR) products prepared with different methods (kneading and spray drying) changes the morphology of original drug. The product made by spray drying has nearly isodimensional spherical particles, and potentially better flowability than the kneaded product. Spray drying of PAR product without β-CD shows similar morphology like a product with β-CD, but the particles show a greater inclination to adhesion. The results were obtained by electron microscopic study.     

CHANGES IN CARBOHYDRATES OF ALFALFA DURING ARTIFICIAL DRYING

SUMMARY —The present study was undertaken to examine the effect of different temperatures and duration of artificial drying treatment of herbage tissue on changes of some carbohydrates, lignin and methoxyls. Significant changes were established with seven of ten constituents examined. The contents of monosaccharides, disaccharides, starch and hemicellulose were lower in the samples of dehydrated alfalfa than in the samples of fresh herbage tissue under all experimental conditions. Protopectin content was lower in all samples of dried alfalfa, except when samples of fresh herbage tissue were dried at extremely high temperatures to a final moisture level below 4%. On the contrary, the content of free galacturonic acid was higher in all samples, except under the latter mentioned conditions. Cellulose content decreased in the herbage tissue during artificial drying, except when drying was conducted at higher temperatures and longer periods; that is, when the herbage tissue was dried to a moisture level below 7%. The contents of pectin, lignin and methoxyls did not show regularity of quantitative change during the artificial drying of herbage tissue. Duration of temperature was one of the main factors, other than temperature, affecting the change in constituents and was directly related to the final moisture level of dried herbage tissue.     

Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo

The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and its main metabolites 4-hydroxyospemifene and 4′-hydroxyospemifene weakly inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at clinically relevant concentrations. Induction of CYPs by ospemifene in cultured human hepatocytes was 2.4-fold or less. The in vivo studies showed that ospemifene did not have significant effects on the areas under the plasma concentration-time curves of the tested CYP substrates warfarin (CYP2C9), bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with ospemifene did not alter their metabolism. Therefore, the risk that ospemifene will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is low.