PURPOSE: Imaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution. METHODS: Magnetic resonance imaging, ATR-FTIR spectroscopic imaging and Raman mapping have been used to study the release mechanism of a poorly water soluble drug, aprepitant, from multicomponent amorphous solid dispersions. Solid dispersions were prepared based on the combination of two selected polymers - Soluplus, as a solubilizer, and PVP, as a dissolution enhancer. Formulations were prepared in a ratio of Soluplus:PVP 1:10, 1:5, 1:3, and 1:1, in order to obtain favorable properties of the polymer carrier. RESULTS: The crystallization of aprepitant during dissolution has occurred to a varying degree in the polymer ratios 1:10, 1:5, and 1:3, but the increasing presence of Soluplus in the formulation delayed the onset of crystallization. The Soluplus:PVP 1:1 solid dispersion proved to be the best matrix studied, combining the abilities of both polymers in a synergistic manner. CONCLUSIONS: Aprepitant dissolution rate has been significantly enhanced. This study highlights the benefits of combining imaging methods in order to understand the release process.
- MeSH
- Chemistry, Pharmaceutical methods MeSH
- Crystallization MeSH
- Magnetic Resonance Imaging methods MeSH
- Morpholines chemistry MeSH
- Drug Carriers chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polymers chemistry MeSH
- Polyvinyls chemistry MeSH
- Pyrrolidines chemistry MeSH
- Solubility MeSH
- Spectroscopy, Fourier Transform Infrared methods MeSH
- Drug Liberation MeSH
- Water chemistry MeSH
- Publication type
- Journal Article MeSH
PURPOSE: Imaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution. METHODS: Magnetic resonance imaging, ATR-FTIR spectroscopic imaging and Raman mapping have been used to study the release mechanism of a poorly water soluble drug, aprepitant, from multicomponent amorphous solid dispersions. Solid dispersions were prepared based on the combination of two selected polymers - Soluplus, as a solubilizer, and PVP, as a dissolution enhancer. Formulations were prepared in a ratio of Soluplus:PVP 1:10, 1:5, 1:3, and 1:1, in order to obtain favorable properties of the polymer carrier. RESULTS: The crystallization of aprepitant during dissolution has occurred to a varying degree in the polymer ratios 1:10, 1:5, and 1:3, but the increasing presence of Soluplus in the formulation delayed the onset of crystallization. The Soluplus:PVP 1:1 solid dispersion proved to be the best matrix studied, combining the abilities of both polymers in a synergistic manner. CONCLUSIONS: Aprepitant dissolution rate has been significantly enhanced. This study highlights the benefits of combining imaging methods in order to understand the release process.
- MeSH
- Aprepitant MeSH
- Chemistry, Pharmaceutical methods MeSH
- Crystallization MeSH
- Magnetic Resonance Imaging methods MeSH
- Morpholines chemistry MeSH
- Drug Carriers chemistry MeSH
- Polyethylene Glycols chemistry MeSH
- Polymers chemistry MeSH
- Polyvinyls chemistry MeSH
- Pyrrolidines chemistry MeSH
- Solubility MeSH
- Spectroscopy, Fourier Transform Infrared methods MeSH
- Drug Liberation MeSH
- Water chemistry MeSH
- Publication type
- Journal Article MeSH
This review article aims to address the main features of breast cancer. Thus, the general aspects of this disease have been shown since the first evidence of breast cancer in the world until the numbers today. In this way, there are some ways to prevent breast cancer, such as the woman's lifestyle (healthy eating habits and physical activities) that helps to reduce the incidence of this anomaly. The first noticeable symptom of this anomaly is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer are discovered when the woman feels a lump being present and about 90% of the cases, the cancer is noticed by the woman herself. Currently, the most used method for the detection of cancer and other injuries is the Magnetic Resonance Imaging (MRI) technique. This technique has been shown to be very effective, however, for a better visualization of the images, Contrast Agents (CAs) are used, which are paramagnetic compounds capable of increasing the relaxation of the hydrogen atoms of the water molecules present in the body tissues. The most used CAs are Gd3+ complexes, although they are very efficient, they are toxic to the organism. Thus, new contrast agents have been studied to replace Gd3+ complexes; we can mention iron oxides as a promising substitute.
- MeSH
- Contrast Media * MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Breast Neoplasms * diagnostic imaging MeSH
- Water MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Efficient tablet disintegration is a pre-requisite for fast and complete drug dissolution from immediate release formulations. While the overall tablet disintegration time is a routinely measured quality attribute of pharmaceutical products, little attention is usually paid to the analysis of disintegration fragments and the cascade of elementary steps that lead to their formation. In this work, we investigate the disintegration pathways of directly compressed tablets by a unique combination of three methods: (i) magnetic resonance imaging (MRI), to gain insight into structural changes of tablets during disintegration; (ii) texture analysis, to measure the disintegration kinetics; and (iii) static light scattering, to characterise the size distribution of disintegration fragments. By systematically varying the tablet composition (50-90% of ibuprofen as a model active ingredient, 0-4% of croscarmellose sodium disintegrant, 6-50% of lactose monohydrate filler), a relationship between the tablet formulation, the size distribution of the disintegration fragments and the dissolution rate of the active ingredient has been established. To interpret the experimental observations, we analyse the disintegration fragments by Raman mapping and relate their composition and structure to the micro-scale arrangement of individual formulation components inside the tablet.
- MeSH
- Chemistry, Pharmaceutical * MeSH
- Magnetic Resonance Imaging MeSH
- Excipients * MeSH
- Solubility MeSH
- Tablets MeSH
- Publication type
- Journal Article MeSH
Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore, the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin αVβ3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labeled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalization, and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG αVβ3- and A431-CCK2R expressing tumor xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumor uptake accompanied by slow blood clearance and retention in nontargeted tissues (spleen, liver, and kidneys) leading to visualization of tumors at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine-tune pharmacokinetics are needed to translate this into a clinical setting.
- MeSH
- Chelating Agents chemistry pharmacokinetics MeSH
- Heterografts MeSH
- Integrin alphaVbeta3 metabolism MeSH
- Hydroxamic Acids pharmacokinetics MeSH
- Humans MeSH
- Molecular Probes chemistry pharmacokinetics MeSH
- Multimodal Imaging methods MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Neoplasms diagnostic imaging metabolism MeSH
- Positron Emission Tomography Computed Tomography MeSH
- Gallium Radioisotopes pharmacokinetics MeSH
- Receptor, Cholecystokinin B metabolism MeSH
- Ferric Compounds pharmacokinetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
In clinical practice the imaging of bone tissue is based almost exclusively on x-ray or radiochemical methods. Alternative methods, such as MRI and optical imaging, can provide not only anatomical, but also physiological information, due to their ability to reflect the properties of body fluids (temperature, pH and concentration of ions). In this article we review bone targeting probes for MRI and fluorescence imaging. As bone targeting is mainly associated with phosphonate and bisphosphonate derivatives, we also focus on their sorption behavior. Also discussed in detail is the limitation of using bone-targeting probes for MRI and optical imaging mainly due to their long-time retention in bone tissue and the low permeability of tissues for light.
- MeSH
- Fluorescent Dyes chemistry metabolism MeSH
- Bone and Bones cytology metabolism MeSH
- Metals chemistry MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Molecular Structure MeSH
- Molecular Imaging methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Spectroscopic imaging (SI) is a method that enables the measurement of the spatial distribution of metabolite concentrations in tissue. In this paper, an overview of measurement and processing techniques for SI is given. First, the basic structure of SI pulse sequences is introduced and the concepts of k-space, point spread function and spatial resolution are described. Then, special techniques are presented for the purpose of eliminating spurious signals and reducing measurement time. Finally, basic post-processing of SI data and the methods for viewing the results of SI measurement are summarized.
- MeSH
- Artifacts MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Brain Mapping methods MeSH
- Brain Chemistry MeSH
- Brain metabolism MeSH
- Signal Processing, Computer-Assisted MeSH
- Body Water metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
... book xix -- 1 What is organic chemistry? ... ... 1069 -- 41 Asymmetric synthesis 1102 -- 42 Organic chemistry of life 1134 -- 43 Organic chemistry today ... ... What is organic chemistry? ... ... 1 -- Organic chemistry and you 1 -- Organic compounds 2 -- Organic chemistry and industry 6 -- Organic ... ... chemistry and the periodic table 11 -- Organic chemistry and this book 13 -- Further reading I3 -- ? ...
Second edition xxv, 1234 stran : ilustrace ; 28 cm
- Conspectus
- Organická chemie
- NML Fields
- chemie, klinická chemie
- NML Publication type
- učebnice vysokých škol
Recent developments in the prediction of local aerosol deposition in human lungs are driven by the fast development of computational simulations. Although such simulations provide results in unbeatable resolution, significant differences among distinct methods of calculation emphasize the need for highly precise experimental data in order to specify boundary conditions and for validation purposes. This paper reviews and critically evaluates available methods for the measurement of single and disperse two-phase flows for the study of respiratory airflow and deposition of inhaled particles, performed both in vivo and in replicas of airways. Limitations and possibilities associated with the experimental methods are discussed and aspects of the computational calculations that can be validated are indicated. The review classifies the methods into following categories: 1) point-wise and planar methods for velocimetry in the airways, 2) classic methods for the measurement of the regional distribution of inhaled particles, 3) standard medical imaging methods applicable to the measurement of the regional aerosol distribution and 4) emerging and nonconventional methods. All methods are described, applications in human airways studies are illustrated, and recommendations for the most useful applications of each method are given.
- MeSH
- Respiratory Tract Absorption MeSH
- Aerosols chemistry MeSH
- Administration, Inhalation MeSH
- Models, Biological MeSH
- Chemistry, Pharmaceutical methods MeSH
- Hydrodynamics MeSH
- Laryngeal Masks * MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Nebulizers and Vaporizers MeSH
- Permeability MeSH
- Lung drug effects MeSH
- Computer Simulation * MeSH
- Powders chemistry MeSH
- Particle Size MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cyclodextrins are macrocyclic molecules able to form host-guest complexes due to their hydrophobic cavity. Because of their carbohydrate nature they do not absorb light in the UV-vis region (200-800nm), but they can be converted into spectroscopically active compounds via modification with a chromophore unit. Among the chromophores, the group of fluorophores can provide high sensitivity in analytical applications (chemosensing) and low detection limit in optical imaging methods (fluorescent microscopy). Fluorophore-tagged cyclodextrins therefore combine interesting spectroscopic properties with promising supramolecular features which make these conjugates widely applicable in various pharmaceutical fields. The aim of this work is to review the various types of fluorophores which have been used for cyclodextrin tagging, to discuss the synthetic strategies used for the conjugation and to summarize the pharmaceutical applications of these 'visualized' macrocycles including their use in photodynamic therapy. The recent achievements in studying how the fluorophore-appended cyclodextrin derivatives cross biological barriers are also reviewed.
