Over-blending effect of lubricants on capsules manufacturing: a simple and fast wettability technique to predict batch dissolution performance.

Mixing/blending is a crucial operation in the manufacturing of solid drug products in the pharmaceutical industry. Although usually described and controlled in specific steps, blending is also inherent to other operations such as the transference of materials and equipment feeding systems. This study aimed to investigate a simple and fast wettability testing procedure capable to foresee the potential over-blending effects of lubricants occurring during the manufacturing of solid dosage forms. An industrial batch blend was submitted to two mixing mechanisms studies (diffusion and shear) during increasing time periods, and the developed wettability testing procedure was applied to assess their impact on blend water uptake. Capsules filled with these blends were tested for dissolution and disintegration. The method was applied to capsules with known dissolution results manufactured at an industrial scale. Results demonstrated that processes inducing shear stress led to less permeable blends with consequent retardation on capsules dissolution of at least 35% in the tested timepoints and obtained study metrics above 500 s. Moreover, disintegration testing was not able to detect non-compliant dissolutions, while the proposed wettability testing procedure proved to be able to identify performance failures. Wettability results correlate the effect of mixing mechanisms to capsules dissolution performance, evidencing that this technique can be applied in the pharmaceutical industry to evaluate possible over-blending effects.

Highly sensitive thermoelectric touch sensor based on p-type SnO x thin film.

Here, the ability of using p-type tin oxide (SnO x ) thin films as a thermal sensor has been investigated. Firstly, the thermoelectric performance was optimized by controlling the thickness of the SnO x film from 60 up to 160 nm. A high Seebeck coefficient of +263 µV K-1 and electrical conductivity of 4.1 × 102 (S m-1) were achieved in a 60 nm thick SnO x film, due to a compact nanostructured film and the absence of the Sn metallic phase, which was observed for the thicker SnO x film leading to a typical thermoelectric transport properties of a n-type Sn film. Moreover, x-ray photoelectron spectroscopy revealed the co-existence of SnO (79.7%) and SnO2 (20.3%) phases in the 60 nm thick SnO x film, while the optical measurements revealed an indirect gap of 1.8 eV and a direct gap of 2.7 eV, respectively. The 60 nm-SnO x thin film have been tested as a thermoelectric touch sensor, achieving a Vsignal /Vnoise  ≈ 20, with a rise time <1 s. Therefore, this work provides an efficient way for developing highly efficient thermal sensors with potential use in display technologies.

SiGe layer thickness effect on the structural and optical properties of well-organized SiGe/SiO2 multilayers.

In this work, we report on the production of regular (SiGe/SiO2)20 multilayer structures by conventional RF-magnetron sputtering, at 350 °C. Transmission electron microscopy, scanning transmission electron microscopy, raman spectroscopy, and x-ray reflectometry measurements revealed that annealing at a temperature of 1000 °C leads to the formation of SiGe nanocrystals between SiO2 thin layers with good multilayer stability. Reducing the nominal SiGe layer thickness (t SiGe) from 3.5-2 nm results in a transition from continuous SiGe crystalline layer (t SiGe ∼ 3.5 nm) to layers consisting of isolated nanocrystals (t SiGe ∼ 2 nm). Namely, in the latter case, the presence of SiGe nanocrystals ∼3-8 nm in size, is observed. Spectroscopic ellipsometry was applied to determine the evolution of the onset in the effective optical absorption, as well as the dielectric function, in SiGe multilayers as a function of the SiGe thickness. A clear blue-shift in the optical absorption is observed for t SiGe ∼ 2 nm multilayer, as a consequence of the presence of isolated nanocrystals. Furthermore, the observed near infrared values of n = 2.8 and k = 1.5 are lower than those of bulk SiGe compounds, suggesting the presence of electronic confinement effects in the nanocrystals. The low temperature (70 K) photoluminescence measurements performed on annealed SiGe/SiO2 nanostructures show an emission band located between 0.7-0.9 eV associated with the development of interface states between the formed nanocrystals and surrounding amorphous matrix.

Mn-doped ZnO nanocrystals embedded in Al2O3: structural and electrical properties.

We report on the structural and electrical properties of Mn-doped ZnO/Al(2)O(3) nanostructures produced by the pulsed laser deposition technique. Grazing incidence small angle x-ray scattering (GISAXS) and Rutherford backscattering spectrometry revealed the multilayered structure in as-deposited samples. Annealing of the nanostructures was shown to promote the formation of nanocrystals embedded in the Al(2)O(3) matrix, as was evidenced by GISAXS and high resolution transmission microscopy. Particle-induced x-ray emission analysis showed a doping of 8 at.% Mn in ZnO. Grazing incidence x-ray diffraction and Raman spectroscopy demonstrated that the nanocrystals have the pure wurtzite ZnMnO crystalline phase. Resonant Raman scattering displayed an increase of intensity of the 1LO mode as well as broadening of the 2LO mode related to the size effect. Capacitance-voltage measurements showed carrier retention with a voltage shift higher than those reported for similar systems.

Investigation of surface plasmon resonance in gold/alumina composite films prepared by rf-sputtering.

Alumina films containing gold nanoparticles (NPs) were grown by magnetron radio frequency (rf) sputtering technique. They were investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD) and optical absorption spectroscopy. It is suggested that the increase of the contrast of surface plasmon resonance band after annealing is connected with increasing of electron free mean path in Au NPs rather than with change in particle size distribution. The absorption spectra of the nanocomposites have been modelled taking into account a correction of the dielectric constant for electron mean free path limitation.

Electrical conduction of CdSe nanocrystals embedded in silicon oxide films.

In this paper we report on the structural, optical and electrical properties of CdSe nanocrystals (NCs) embedded in silica matrix grown by the rf-magnetron sputtering technique with subsequent annealing under argon flux. Grazing incidence X-ray diffraction (GIXD), Photoluminescence (PL) and Raman spectroscopy, as well as current-voltage (I-V) measurements were used to characterize the CdSe NCs. The PL spectra of annealed samples demonstrate the presence of peaks in the range of 550-620 nm, indicating the quantum confinement effect in CdSe NCs. This quantum confinement effect in CdSe NCs was also confirmed by Raman spectroscopy. Finally, I-V behavior was explained by different concentrations and sizes of CdSe NCs.

Physical and optical characterization of Er3+ doped lead-zinc-borate glass.

This paper reports on the systematic optical characterization of Er3+ (1.0%) doped lead-zinc-borate glass from the measured absorption, luminescence and fluorescence lifetime decay curve profiles. By the application of the Judd-Ofelt theory, spectral intensities of the absorption bands have been analysed and these absorption results have been used in evaluating the luminescence properties of the Er3+ doped lead-zinc-borate glass. Stimulated emission cross-sections (sigmapE) of the measured emission transitions have been computed. Based on the measured glass density, and refractive indices, other related physical parameters have also been evaluated. Further, the structural and morphology of the glass material have also been investigated from X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy analysis.

Absorption and emission analysis of RE3+(Sm3+ and Dy3+): lithium boro tellurite glasses.

This paper reports on the development and spectral analysis of Sm3+ (1.0%) and Dy3+ (1.0%) doped lithium-boro-tellurite glasses. A bright orange (4G5/2-->6H7/2) along with a red (4G5/2-->6H9/2) and a yellow (4G5/2-->6H5/2) emission transition have been measured from Sm3+ doped lithium-boro-tellurite glass. Both blue (4F9/2-->6H15/2) and yellow (4F9/2-->6H13/2) emission bands have been obtained from Dy3+ glass. From the measured decay profiles, the lifetimes of the emissions of the Sm3+ glass (4G5/2-->6H5/2, 7/2, 9/2 and 11/2) at an excitation of 401 nm have been found to be in the range 0.47-0.81 ms, and with respect to the Dy3+ emissions (4F9/2-->6H15/2 and 13/2), with excitation at 450 nm, are measured to be in the range of 0.302-0.307 ms. Stimulated emission cross-sections (sigmapE) of the measured emission transitions have also been computed and the values are in the range of (0.38-1.20) x 10(-20) cm2 for Sm3+ and for Dy3+ doped lithium-boro-tellurite glass the values are (0.66-1.39) x 10(-20) cm2.

Structural and optical properties of ge nanocrystals embedded in Al2O3.

Ge nanocrystals (NCs) embedded in aluminum oxide were grown by RF-magnetron sputtering. Raman, high resolution transmission electron microscopy (HRTEM), selected area diffraction (SAD), and X-ray diffraction (XRD) techniques confirmed good cristallinity of the NCs from samples annealed at 800 degrees C. The average NC size was estimated to be around 7 nm. Photoluminescence (PL) measurements show an emission related to the NCs. The temperature dependence of the PL confirms the confinement phenomenon in the Ge NCs.

Hysteretic Characteristics of Pulsed Laser Deposited 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3/ZnO Bilayers.

In the present work, we study the hysteretic behavior in the electric-field-dependent capacitance and the current characteristics of 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (BCZT)/ZnO bilayers deposited on 0.7 wt % Nb-doped (001)-SrTiO3 (Nb:STO) substrates in a metal-ferroelectric-semiconductor (MFS) configuration. The X-ray diffraction measurements show that the BCZT and ZnO layers are highly oriented along the c-axis and have a single perovskite and wurtzite phases, respectively, whereas high-resolution transmission electron microscopy revealed very sharp Nb:STO/BCZT/ZnO interfaces. The capacitance-electric field ( C- E) characteristics of the bilayers exhibit a memory window of 47 kV/cm and a capacitance decrease of 22%, at a negative bias. The later result is explained by the formation of a depletion region in the ZnO layer. Moreover, an unusual resistive switching (RS) behavior is observed in the BCZT films, where the RS ratio can be 500 times enhanced in the BCZT/ZnO bilayers. The RS enhancement can be understood by the barrier potential profile modulation at the depletion region, in the BCZT/ZnO junction, via ferroelectric polarization switching of the BCZT layer. This work builds a bridge between the hysteretic behavior observed either in the C- E and current-electric field characteristics on a MFS structure.

Enhanced resistive switching characteristics in Pt/BaTiO3/ITO structures through insertion of HfO2:Al2O3 (HAO) dielectric thin layer.

An enhanced resistive switching (RS) effect is observed in Pt/BaTiO3(BTO)/ITO ferroelectric structures when a thin HfO2:Al2O3 (HAO) dielectric layer is inserted between Pt and BTO. The P-E hysteresis loops reveal the ferroelectric nature of both Pt/BTO/ITO and Pt/HAO/BTO/ITO structures. The relation between the RS and the polarization reversal is investigated at various temperatures in the Pt/HAO/BTO/ITO structure. It is found that the polarization reversal induces a barrier variation in the Pt/HAO/BTO interface and causes enhanced RS, which is suppressed at Curie temperature (Tc = 140 °C). Furthermore, the Pt/HAO/BTO/ITO structures show promising endurance characteristics, with a RS ratio >103 after 109 switching cycles, that make them potential candidates for resistive switching memory devices. By combining ferroelectric and dielectric layers this work provides an efficient way for developing highly efficient ferroelectric-based RS memory devices.

Acute exercise amplifies inflammation in obese patients with COPD.

Systemic inflammation has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) systemic effects. However, most COPD patients do not suffer from persistent systemic inflammation even after exacerbations and exercise and scientific evidence has provided conflicting results. Our aim is to evaluate inflammatory gene expression at rest and at 1 and 24h after strenuous exercise in COPD patients and study the patient variables associated with inflammatory expression. A cross-sectional study was conducted in COPD patients who were recruited on entry to a pulmonary rehabilitation (PR) program. Demographic, clinical and functional data were collected. Blood samples were collected and gene expression was analyzed by reverse transcriptase polymerase chain reaction for IFNg, IL1b, IL6, IL8, TNFa, TGFb1 and iNOS. The study included 21 patients (15 men, 71.4%), mean age 66.1 years old (SD=8.27), mean FEV1 46.76% (SD 20.90%), 67% belonging to GOLD grade D, mean BODE index of 3.9, 90.5% with smoking history, mean BMI 25.81 (SD=4.87), median of 1.29 exacerbations in the previous year. There was no statistical significant difference between inflammatory expression at rest and at 1h and 24h after the maximal exercise test for all tested genes. We found an association between BMI and inflammatory expression at all the points of time checked, a slight inverse association occurs with low BMI for mRNA IL1b, IL6, TNFa, TGFb1 and iNOS, and there was a more pronounced positive association for obese patients for all tested genes. This preliminary study did not show an enhanced inflammatory gene expression from rest to 1h and 24h after short-term exercise, but did show an increased inflammatory gene expression in both BMI extremes, both at rest and after exercise, suggesting not only malnourishment, but also obesity as potential links between COPD and systemic inflammation. Studies with larger samples and designed to definitely exclude OSA or OHS as confounding factors in obese patients are required.

In vivo dual-delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy.

Oral delivery of proteins is still a challenge in the pharmaceutical field. Nanoparticles are among the most promising carrier systems for the oral delivery of proteins by increasing their oral bioavailability. However, most of the existent data regarding nanosystems for oral protein delivery is from in vitro studies, lacking in vivo experiments to evaluate the efficacy of these systems. Herein, a multifunctional composite system, tailored by droplet microfluidics, was used for dual delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 inhibitor (iDPP4) in vivo. Oral delivery of GLP-1 with nano- or micro-systems has been studied before, but the simultaneous nanodelivery of GLP-1 with iDPP4 is a novel strategy presented here. The type 2 diabetes mellitus (T2DM) rat model, induced through the combined administration of streptozotocin and nicotinamide, a non-obese model of T2DM, was used. The combination of both drugs resulted in an increase in the hypoglycemic effects in a sustained, but prolonged manner, where the iDPP4 improved the therapeutic efficacy of GLP-1. Four hours after the oral administration of the system, blood glucose levels were decreased by 44%, and were constant for another 4 h, representing half of the glucose area under the curve when compared to the control. An enhancement of the plasmatic insulin levels was also observed 6 h after the oral administration of the dual-drug composite system and, although no statistically significant differences existed, the amount of pancreatic insulin was also higher. These are promising results for the oral delivery of GLP-1 to be pursued further in a chronic diabetic model study.

The appearance of donor heparin in the recipient after reperfusion of a liver graft.

The release of heparin has been mentioned as one of the causes of hypocoagulability after reperfusion of the liver graft. It has been ascribed to endogenous heparin released from the donor liver or to exogenous heparin in the preservation fluid that is released into the recipient after sequestration into the graft during preservation. The aim of this study was to investigate whether systemic administration of heparin to the donor before the hepatectomy contributes to the appearance of heparin in the recipient after reperfusion. We studied 20 patients undergoing an auxiliary heterotopic liver transplantation; 15 donors had received heparin immediately before circulation arrest (median 300 IU/kg body weight), but 5 had not. The thrombin time (TT), activated partial thromboplastin time (aPTT), and heparin neutralization test were determined at several intervals during the transplantation.

Mild haemostatic problems associated with congenital heterozygous alpha 2-antiplasmin deficiency.

A Dutch family, of which 13 members are heterozygotes, deficient for alpha 2-antiplasmin (alpha 2-AP) is reported. Clinical studies showed that 2 heterozygotes had a mild bleeding tendency, which presented as bleeding episodes after tooth extraction and after surgery and, in one patient, also as excessive menstruation. Laboratory investigations revealed an alpha 2-AP activity of 62% (51-71) (median and range) and an antigen level of 60% (60-66). The plasminogen binding as well as the fibrin binding properties of alpha 2-AP were normal. Plasminogen concentrations were significantly higher in the heterozygotes compared to the other family members. However, free plasminogen not bound to histidine-rich glycoprotein was not significantly different between these two groups. We propose that in this family the deficiency of alpha 2-AP is due to a decreased synthesis of a normal alpha 2-AP molecule. This present study brings the frequency of heterozygous alpha 2-AP deficient patients with a bleeding tendency to 13 out of 59 heterozygotes reported in the literature.

Intravascular coagulation in liver transplantation--is it present or not? A comparison between orthotopic and heterotopic liver transplantation.

UNLABELLED: It is still not clear whether disseminated intravascular coagulation (DIC) contributes to the hemostatic disturbances in orthotopic liver transplantation (OLT). Theoretically the lack of hepatic clearance of procoagulant factors during the anhepatic period and the release of thromboplastic material from the graft might trigger DIC. During heterotopic liver transplantation (HLT) the host liver is left in situ and procoagulant factors may still be cleared; DIC, if present, may not occur until after reperfusion. The aim of the present study was to gain more insight into the underlying mechanism of the coagulation changes during liver transplantation by comparison of OLT and HLT. Thrombin-antithrombin-III complexes (TAT), and indicator of thrombin generation, fibrin degradation products (FbDP) and routine clotting times were assayed in 12 OLTs, 18 HLTs and in a control group of 10 partial hepatic resections (PHR). TAT increased dramatically after reperfusion to 136 micrograms/l in OLT and to 94 micrograms/l in HLT (p n.s.). In contrast, FbDP levels increased only in OLT, to a maximum of 13.8 micrograms/ml. Routine clotting times changed mildly and similarly in both OLT and HLT. CONCLUSIONS: Graft reperfusion triggers excessive thrombin formation, but there are no other signs of subsequent DIC. Any thrombin formed is probably rapidly inhibited by antithrombin-III. The rise in FbDP during OLT is the result of increased fibrinolysis, which occurred only in OLT and not in HLT.

Control of endophagic Anopheles mosquitoes and human malaria in Guinea Bissau, West Africa by permethrin-treated bed nets.

We compared the anti-mosquito and antimalarial potentialities of placebo-treated versus permethrin-impregnated bed nets in north-western Guinea Bissau. Baseline, pre-intervention entomological and parasitological data were collected during the rainy season of 1990 and bed nets were distributed shortly before the rainy season of 1991. Pairs of 3 ethnically different villages were investigated. The villages in each pair were at least 2 km apart but belonged to the same ethnic group in an ecologically similar area. After one year permethrin-treated bed nets were provided to all people in one village of each pair and placebo-treated bed nets to the other villages. About 98% of mosquitoes caught in bedrooms belonged to Anopheles gambiae and A. melas, which we consider to be the main malaria vectors in the study villages. Mean Plasmodium falciparum sporozoite rate in A. gambiae (9.6%) and A. melas (12.4%) was highest during October-November. The Plasmodium index in children 2-9 years old in the 6 villages, at the end of the rainy season 1990, ranged between 44% and 79%. Of these, 98% were identified as P. falciparum, 1% as P. malariae and 1% as mixed infections of these species. Significant reductions of Anopheles indoor resting densities and malaria parasite rates in humans were recorded in villages which had received permethrin-treated nets, but not in the control villages. The mean number of P. falciparum-infective mosquito bites received indoors in untreated villages during the rainy season was estimated to be about 4 per child and 20 per adult. This inoculation rate was reduced by at least 78% by the use of permethrin-impregnated bed nets. The malaria parasite rates and proportions of people experiencing 'disease with fever' decreased significantly in villages provided with permethrin-treated nets but not in the control villages. Impregnated nets may be an important tool to reduce disease and death due to malaria in Guinea Bissau.

[Extrapulmonary tuberculosis]. / Tuberculose extrapulmonar.

Although the respiratory tract is the major site for tuberculous lesions, all organs can be affected. The authors review the clinical files of 25 patients admitted to our Department with lung and/or pleural tuberculous disease, confirmed by bacteriology or histopathology, who simultaneously suffered from tuberculosis in other organs. We included 20 men and 5 women, aged from 10 to 74 years (mean: 37.12 years); 6 patients had pleural tuberculosis, 19 had pulmonary tuberculosis, 4 of them having miliary tuberculosis. Lymph node tuberculosis was diagnosed in 14 patients, tuberculosis of the bones in 4, laryngeal tuberculosis in 3 patients, tuberculous pericarditis in 2 patients, epididymitis in 1 and intestinal in another patient. Several clinical aspects are discussed, namely diagnostic procedures, M. tuberculosis identification in inflammatory exudates in 6 patients, in urine in 1, and in histopathology in 9 patients; in the 9 remaining patients extrapulmonary tuberculosis was accepted considering clinical and radiological findings in patients with respiratory tract tuberculosis. We concluded that tuberculosis may still assume severe clinical forms and that patients with tuberculosis should be globally evaluated.

[Diagnosis of illiteracy in patients hospitalized at a nursing service. Prospective study]. / Diagnóstico de analfabetismo nos doentes internados numa enfermaria. Estudo prospectivo.

UNLABELLED: When, at the end of a medical visit, a doctor prescribes medication, he may be unaware that writing is unknown to the patient. This fact compromises the patient's understanding of disease and therapeutics and thus the importance of diagnosing illiteracy. The A.A studied prospectively 200 consecutive patients admitted to a Medical Ward at Santa Maria Hospital in Lisbon, from 13/3/1997 to 8/7/1998. The study included age, gender, social environment, evaluation of the ability to read and write, years of scholarship and the principal diagnosis. The results were to chi 2 (Yates) and Student's T-tests. RESULTS: 94 patients were male and 106 female, aged between 18 and 95 years (mean 62.3), 106 from an urban environment, 54 from a rural environment and 37 had lived their adult life in a rural environment but were at present living in an urban environment. The percentage of illiteracy was 30.5%, being considerably higher in the females (43.4%) than in the males (15.96%), in patients above 65 years (49%) compared to patients from 15 to 64 years old (12%), in non-urban patients (55%) opposed to urban born patients (10.4%). Any of these variables, gender, age and social environments had statistical significance to P < 0.001 when associated to illiteracy. CONCLUSIONS: The comparative analysis of the official results for the general Portuguese Population study, Census 91, shows an important analogy. In both studies illiteracy was worst in females and in those above 65 years of age. Today illiteracy is still days a serious National problem, with important medical implications, a troublesome obstacle to the understanding of the disease and compliance with therapy.

[Pulmonary lymphangioleiomyomatosis]. / Linfangioleiomiomatose pulmonar.

The authors present a clinical case of Lymphangioleiomyomatosis of the lung. They analyse the clinical, radiological and functional features and comment on the evolution and therapeutic approach of this rare disorder. To the authors, lung involvement as well as therapeutic decision are important features that affect the prognosis.