Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ultrasound guidance is not necessary during easy embryo transfers

Purpose: To determine whether the use of ultrasound (US) to guide embryo transfer (ET) in a population previously defined as likely to have easy transfer would change the implantation and pregnancy rates in an ICSI program.Methods: A total of 100 patients identified as likely to have easy transfer after mock transfer were divided into two groups: Group I, US-guided ET (N = 50) and Group II, ET without the aid of US (N = 50).Results: Implantation and pregnancy rates were similar (p = 0.51, p = 0.29) for Group I (19.6%,42%) and Group II (16.3%,30%), as also was the abortion rate (p = 0.55) (Group I: 1/21; Group II: 2/15).Conclusion: As long as previous mock transfers are routinely performed during a cycle preceding assisted reproduction and the clinician considers transfer to be easy, ultrasound does not benefit the process of embryo transfer.

A kinetic model for the ultrasound catalyzed hydrolysis of solventless TEOS-water mixtures and the role of the initial additions of ethanol

The acid and ultrasound catalyzed hydrolysis of solventless TEOS-water mixtures are studied, as a function of the initial additions of ethanol to the mixtures, by means of flux calorimetry measurements. A device was specially designed for this purpose. Under acid conditions, our proposed method has been able to resolve hydrolysis from other condensation reactions, by detecting the exothermal hydrolysis reaction heat. The process has been explained by a dissolution and reaction mechanism. Ultrasound forces the dissolution process to start the reaction. The alcohol produced in the reaction helps the dissolution process to further enhance the hydrolysis. Initial amounts of pure ethanol added to the mixtures shorten the start time of the reaction, due to an additional effect of dissolution, and diminish the reaction rate, as a result of the solvent dilution effect. Our dissolution and reaction mechanism modeling describes the main points arising from the experimental data and yields k(H) = 0.24 M(-1) min(-1) for the second-order hydrolysis rate constant at 39 degrees C.

Effects of the water quantity on the solventless TEOS hydrolysis under ultrasound stimulation

The acid hydrolysis under ultrasound stimulation of solventless tetraethoxysilane(TEOS)-water mixtures was studied at 40 degrees C, by means of a heat flux calorimetric method, as a function of the initial water/TEOS molar ratio (r) ranging from 2 to 10. The method is based on the time record of the exothermic heat peak of hydrolysis, arising after an induction time under ultrasound stimulation, which is a measure of the reaction rate. The hydrolysed quantity was found to be approximately independent of the water/TEOS molar ratio, even for r < 4. Polycondensation reaction takes place mainly for low water/TEOS molar ratio in order to supply water to allow almost complete hydrolysis. The overall process of dissolution and hydrolysis has reasonably been described by a previous modelling. The dissolution process of water in TEOS, under ultrasound stimulation and acid conditions, was found to be rather dependent of the alcohol produced in the hydrolysis reaction instead of the initial water quantity present in the mixture.

A study of the hydrolysis pathway in oxalic acid catalyzed reacting TMOS-water mixtures under ultrasound stimulation

The hydrolysis of TMOS in oxalic acid catalyzed reacting TMOS-water mixtures, under ultrasound stimulation, was studied by fitting a simplified dissolution and reaction modeling for samples, the hydrolysis rate of which had been measured in a previous work. The reaction pathway represented in a ternary diagram shows a heterogeneous step for the reaction which gradually progresses until complete homogenization of the system. Besides the water dissolved due to the homogenizing effect of the alcohol, ultrasound maintains a virtual and additional dissolution of water located at the interface between the TMOS and water during the heterogeneous step of the reaction. The mean radius of the heterogeneity represented by water dispersed in TMOS was evaluated as around 150 Angstrom. The oxalic acid concentration accordingly increases the hydrolysis rate constant but its fundamental role on the solubility of water in TMOS could not unequivocally be established.

A kinetic study of the effect of ultrasound power on the sonohydrolysis of tetraethyl orthosilicate

A kinetic study of the ultrasound-stimulated and acid-catalyzed sonohydrolysis of tetraethyl orthosilicate (TEOS) in solventless TEOS-water heterogeneous mixtures was carried out by means of a calorimetric method as a function of the ultrasound power. The hydrolysis reaction starts in acidulated heterogeneous water-TEOS mixtures after an induction period under ultrasonic stimulation. The ultrasound power seems to play a role on the dynamical coupling of the system originating a continuum upward shifting of the base line during the induction period of sonication. The rate in which the base line is upward shifted diminishes with the power. The best coupling between the ultrasound and the reactant heterogeneous mixtures for this experimental setup was found to occur at 50 W, for which the gelation time was found to be a minimum. The kinetics of the heterogeneous TEOS sonohydrolysis was studied on the basis of a dissolution and reaction modeling. The heterogeneous reaction pathway as deduced from the kinetic study was drawn in a ternary diagram as a function of the ultrasound power. (C) 2006 Elsevier B.V. All rights reserved.

Effects of HCl on the ultrasound catalyzed TEOS hydrolysis as determined by a calorimetric study

The acid catalyzed and ultrasound stimulated hydrolysis of solventless tetraethoxysilane-water mixtures was studied at 39°C as a function of HCl added to the mixtures (log[HCl]-1 ranged from 0.8 to 2.0), The reaction was carried out in a specially designed device, in which a steady state heat flow is maintained, while sonication is taking place, if no reaction is expected to occur. The exothermal hydrolysis reaction causes an increasing temperature (ΔTt) as a function of the reaction time, t. The isothermal hydrolysis rate constant, k, has been evaluated from the experimental ΔTt versus t data, after corrections for the increasing temperature effects, by using a method resulting from our theoretical modeling based on a dissolution and reaction mechanism. The hydrolysis rate constant fits closely a k α [H+] law as expected for this kind of hydrogen-ion catalyzed reaction.

Dissolution Enhancement and Characterization of Nimodipine Solid Dispersions with Poloxamer 407 or PEG 6000

The solid dispersion approach is an alternative to increase drug solubility. Many carriers have been studied, but there is few information about poloxamer 407 (P407). Consequently, the objective of this study was to evaluate P407 as a carrier for nimodipine solid dispersions and to compare its solubility and dissolution rates with those from polyethylene glycol (PEG 6000). The solid dispersions were prepared by the hot melting and solvent methods and they were characterized by FTIR, DSC, solubility, and dissolution tests. The results indicated a three-fold increase in solid dispersions solubility in the presence with P407 than those prepared with PEG.

Association of single nucleotide polymorphisms in the bovine leptin and leptin receptor genes with growth and ultrasound carcass traits in Nellore cattle

Given the important role of leptin in metabolism, we looked for a possible association of leptin and leptin receptor polymorphisms with carcass and growth traits in Nellore cattle. We examined associations of leptin and leptin receptor SNPs with ultrasound carcass (longissimus dorsi muscle area (ribeye area), backfat thickness and rump fat thickness and growth traits (weaning weight adjusted to 210 days of age, yearling weight adjusted to 550 days of age, weight gain of weaning to yearling and scrotal circumference adjusted to 550 days of age) of 2162 Bos primigenius indicus (Nellore) animals. Allele and genotypic frequencies were calculated for each marker. Allele substitution, additive and dominance effects of the polymorphisms were also evaluated. Some alleles of the molecular markers had low frequencies, lower than 1%, in the sample analyzed, although the same polymorphisms described for B. p. taurus cattle were found. Due to very low allelic frequencies, the E2JW, A59V and UASMS2 markers were not included in the analysis, because they were almost fixed. E2FB was found to be significantly associated with weight gain, ribeye area and backfat thickness. The promoter region markers, C963T and UASMS1, were also found to be significantly associated with ribeye area. T945M was significantly associated with weight gain. We conclude that the leptin and receptor gene markers would be useful for marker-assisted selection.

Structuring of polymer surface by evaporation of sessile microdrops

In this thesis, we investigated the evaporation of sessile microdroplets on different solid substrates. Three major aspects were studied: the influence of surface hydrophilicity and heterogeneity on the evaporation dynamics for an insoluble solid substrate, the influence of external process parameters and intrinsic material properties on microstructuring of soluble polymer substrates and the influence of an increased area to volume ratio in a microfluidic capillary, when evaporation is hindered. In the first part, the evaporation dynamics of pure sessile water drops on smooth self-assembled monolayers (SAMs) of thiols or disulfides on gold on mica was studied. With increasing surface hydrophilicity the drop stayed pinned longer. Thus, the total evaporation time of a given initial drop volume was shorter, since the drop surface, through which the evaporation occurs, stays longer large. Usually, for a single drop the volume decreased linearly with t1.5, t being the evaporation time, for a diffusion-controlled evaporation process. However, when we measured the total evaporation time, ttot, for multiple droplets with different initial volumes, V0, we found a scaling of the form V0 = attotb. The more hydrophilic the substrate was, the more showed the scaling exponent a tendency to an increased value up to 1.6. This can be attributed to an increasing evaporation rate through a thin water layer in the vicinity of the drop. Under the assumption of a constant temperature at the substrate surface a cooling of the droplet and thus a decreased evaporation rate could be excluded as a reason for the different scaling exponent by simulations performed by F. Schönfeld at the IMM, Mainz. In contrast, for a hairy surface, made of dialkyldisulfide SAMs with different chain lengths and a 1:1 mixture of hydrophilic and hydrophobic end groups (hydroxy versus methyl group), the scaling exponent was found to be ~ 1.4. It increased to ~ 1.5 with increasing hydrophilicity. A reason for this observation can only be speculated: in the case of longer hydrophobic alkyl chains the formation of an air layer between substrate and surface might be favorable. Thus, the heat transport to the substrate might be reduced, leading to a stronger cooling and thus decreased evaporation rate. In the second part, the microstructuring of polystyrene surfaces by drops of toluene, a good solvent, was investigated. For this a novel deposition technique was developed, with which the drop can be deposited with a syringe. The polymer substrate is lying on a motorized table, which picks up the pendant drop by an upward motion until a liquid bridge is formed. A consecutive downward motion of the table after a variable delay, i.e. the contact time between drop and polymer, leads to the deposition of the droplet, which can evaporate. The resulting microstructure is investigated in dependence of the processes parameters, i.e. the approach and the retraction speed of the substrate and the delay between them, and in dependence of the intrinsic material properties, i.e. the molar mass and the type of the polymer/solvent system. The principal equivalence with the microstructuring by the ink-jet technique was demonstrated. For a high approach and retraction speed of 9 mm/s and no delay between them, a concave microtopology was observed. In agreement with the literature, this can be explained by a flow of solvent and the dissolved polymer to the rim of the pinned droplet, where polymer is accumulated. This effect is analogue to the well-known formation of ring-like stains after the evaporation of coffee drops (coffee-stain effect). With decreasing retraction speed down to 10 µm/s the resulting surface topology changes from concave to convex. This can be explained with the increasing dissolution of polymer into the solvent drop prior to the evaporation. If the polymer concentration is high enough, gelation occurs instead of a flow to the rim and the shape of the convex droplet is received. With increasing delay time from below 0 ms to 1s the depth of the concave microwells decreases from 4.6 µm to 3.2 µm. However, a convex surface topology could not be obtained, since for longer delay times the polymer sticks to the tip of the syringe. Thus, by changing the delay time a fine-tuning of the concave structure is accomplished, while by changing the retraction speed a principal change of the microtopolgy can be achieved. We attribute this to an additional flow inside the liquid bridge, which enhanced polymer dissolution. Even if the pendant drop is evaporating about 30 µm above the polymer surface without any contact (non-contact mode), concave structures were observed. Rim heights as high as 33 µm could be generated for exposure times of 20 min. The concave structure exclusively lay above the flat polymer surface outside the structure even after drying. This shows that toluene is taken up permanently. The increasing rim height, rh, with increasing exposure time to the solvent vapor obeys a diffusion law of rh = rh0  tn, with n in the range of 0.46 ~ 0.65. This hints at a non-Fickian swelling process. A detailed analysis showed that the rim height of the concave structure is modulated, unlike for the drop deposition. This is due to the local stress relaxation, which was initiated by the increasing toluene concentration in the extruded polymer surface. By altering the intrinsic material parameters i.e. the polymer molar mass and the polymer/solvent combination, several types of microstructures could be formed. With increasing molar mass from 20.9 kDa to 1.44 MDa the resulting microstructure changed from convex, to a structure with a dimple in the center, to concave, to finally an irregular structure. This observation can be explained if one assumes that the microstructuring is dominated by two opposing effects, a decreasing solubility with increasing polymer molar mass, but an increasing surface tension gradient leading to instabilities of Marangoni-type. Thus, a polymer with a low molar mass close or below the entanglement limit is subject to a high dissolution rate, which leads to fast gelation compared to the evaporation rate. This way a coffee-rim like effect is eliminated early and a convex structure results. For high molar masses the low dissolution rate and the low polymer diffusion might lead to increased surface tension gradients and a typical local pile-up of polymer is found. For intermediate polymer masses around 200 kDa, the dissolution and evaporation rate are comparable and the typical concave microtopology is found. This interpretation was supported by a quantitative estimation of the diffusion coefficient and the evaporation rate. For a different polymer/solvent system, polyethylmethacrylate (PEMA)/ethylacetate (EA), exclusively concave structures were found. Following the statements above this can be interpreted with a lower dissolution rate. At low molar masses the concentration of PEMA in EA most likely never reaches the gelation point. Thus, a concave instead of a convex structure occurs. At the end of this section, the optically properties of such microstructures for a potential application as microlenses are studied with laser scanning confocal microscopy. In the third part, the droplet was confined into a glass microcapillary to avoid evaporation. Since here, due to an increased area to volume ratio, the surface properties of the liquid and the solid walls became important, the influence of the surface hydrophilicity of the wall on the interfacial tension between two immiscible liquid slugs was investigated. For this a novel method for measuring the interfacial tension between the two liquids within the capillary was developed. This technique was demonstrated by measuring the interfacial tensions between slugs of pure water and standard solvents. For toluene, n-hexane and chloroform 36.2, 50.9 and 34.2 mN/m were measured at 20°C, which is in a good agreement with data from the literature. For a slug of hexane in contact with a slug of pure water containing ethanol in a concentration range between 0 and 70 (v/v %), a difference of up to 6 mN/m was found, when compared to commercial ring tensiometry. This discrepancy is still under debate.

Information Filtering for Ultrasound-based Real-time Registration

This paper presents methods based on Information Filters for solving matching problems with emphasis on real-time, or effectively real-time applications. Both applications discussed in this work deal with ultrasound-based rigid registration in computer-assisted orthopedic surgery. In the first application, the usual workflow of rigid registration is reformulated such that registration algorithms would iterate while the surgeon is acquiring ultrasound images of the anatomy to be operated. Using this effectively real-time approach to registration, the surgeon would then receive feedback in order to better gauge the quality of the final registration outcome. The second application considered in this paper circumvents the need to attach physical markers to bones for anatomical referencing. Experiments using anatomical objects immersed in water are performed in order to evaluate and compare the different methods presented herein, using both 2D as well as real-time 3D ultrasound.

Determination of Pelvic Orientation from Ultrasound Images Using Patch-SSMs and a Hierarchical Speed of Sound Compensation Strategy

In the field of computer assisted orthopedic surgery (CAOS) the anterior pelvic plane (APP) is a common concept to determine the pelvic orientation by digitizing distinct pelvic landmarks. As percutaneous palpation is - especially for obese patients - known to be error-prone, B-mode ultrasound (US) imaging could provide an alternative means. Several concepts of using ultrasound imaging to determine the APP landmarks have been introduced. In this paper we present a novel technique, which uses local patch statistical shape models (SSMs) and a hierarchical speed of sound compensation strategy for an accurate determination of the APP. These patches are independently matched and instantiated with respect to associated point clouds derived from the acquired ultrasound images. Potential inaccuracies due to the assumption of a constant speed of sound are compensated by an extended reconstruction scheme. We validated our method with in-vitro studies using a plastic bone covered with a soft-tissue simulation phantom and with a preliminary cadaver trial.