The present work reviews the liquid antisolvent crystallization (LASC) to prepare the nanoparticle of pharmaceutical compounds to enhance their solubility, dissolution rate, and bioavailability. The application of ultrasound and additives is discussed to prepare the particles with narrow size distribution. The use of ionic liquid as an alternative to conventional organic solvent is presented. Herbal compounds, also known for low aqueous solubility and limited clinical application, have been crystalized by LASC and discussed here. The particle characteristics such as particle size and particle size distribution are interpreted in terms of supersaturation, nucleation, and growth phenomena. To overcome the disadvantage of batch crystallization, the scientific literature on continuous flow reactors is also reviewed. LASC in a microfluidic device is emerging as a promising technique. The different design of the microfluidic device and their application in LASC are discussed. The combination of the LASC technique with traditional techniques such as high-pressure homogenization and spray drying is presented. A comparison of product characteristics prepared by LASC and the supercritical CO2 antisolvent method is discussed to show that LASC is an attractive and inexpensive alternative for nanoparticle preparation. One of the major strengths of this paper is a discussion on less-explored applications of LASC in pharmaceutical research to attract the attention of future researchers.
The text is a contemporary continuation of an earlier publication, Kratochvíl B.: Chem. Listy 101, 3 (2007). It describes mainly the nucleation process (two-step nuclea-tion of active substances in pharmacy) and crystallization control processes (seeded crystallization and sonocrystalli-zation). The focus of the work is the description of the nucleation process monitoring by modern analytical tech-nologies, i.e., Focused Beam Reflectance Measurement (FBRM) and the BlazeMetrics system. Both methods pres-ently provide the best available information for a deeper understanding of the nucleation process mechanism in crystallizing active substances. The work is documented by high quality and original photographic attachments of the crystallizing material.
- Klíčová slova
- systém Blaze, nukleace,
- MeSH
- farmaceutická technologie klasifikace metody přístrojové vybavení MeSH
- krystalizace * klasifikace metody přístrojové vybavení MeSH
- lasery MeSH
- výzkumný projekt MeSH
- Publikační typ
- přehledy MeSH
The text is a contemporary continuation of an earlier publication, Kratochvíl B.: Chem. Listy 101, 3 (2007). It describes mainly the nucleation process (two-step nuclea-tion of active substances in pharmacy) and crystallization control processes (seeded crystallization and sonocrystalli-zation). The focus of the work is the description of the nucleation process monitoring by modern analytical tech-nologies, i.e., Focused Beam Reflectance Measurement (FBRM) and the BlazeMetrics system. Both methods pres-ently provide the best available information for a deeper understanding of the nucleation process mechanism in crystallizing active substances. The work is documented by high quality and original photographic attachments of the crystallizing material.Full text English translation is available in the on-line version.
- Klíčová slova
- systém Blaze, nukleace,
- MeSH
- farmaceutická technologie klasifikace metody přístrojové vybavení MeSH
- krystalizace * klasifikace metody přístrojové vybavení MeSH
- lasery MeSH
- výzkumný projekt MeSH
- Publikační typ
- přehledy MeSH
A new co-crystal of pharmaceutical active ingredient Apremilast was successfully designed in this work. The discovered co-crystal with benzoic acid significantly improves key properties like the dissolution and stability of an otherwise poorly soluble Apremilast. A crystallization process was developed, which includes efficient solvent selection and ternary phase diagram construction to minimize risks during scale up. To increase efficiency, we propose that both steps be combined into a single methodology based on solubility data. A suitable solvent for the co-crystallization process was selected and ternary phase diagrams were constructed using three different modifications of thermodynamic model of solid-liquid equilibria. Based on the obtained information, the co-crystallization process was scaled-up to 100 mL. This provides a feasible process to produce larger amounts of this promising pharmaceutical solid form of Apremilast necessary for further drug development.
We demonstrate the use of two nuclear-based analytical methods that can follow the modifications of microstructural arrangement of iron-based metallic glasses (MGs). Despite their amorphous nature, the identification of hyperfine interactions unveils faint structural modifications. For this purpose, we have employed two techniques that utilize nuclear resonance among nuclear levels of a stable 57Fe isotope, namely Mössbauer spectrometry and nuclear forward scattering (NFS) of synchrotron radiation. The effects of heat treatment upon (Fe2.85Co1)77Mo8Cu1B14 MG are discussed using the results of ex situ and in situ experiments, respectively. As both methods are sensitive to hyperfine interactions, information on structural arrangement as well as on magnetic microstructure is readily available. Mössbauer spectrometry performed ex situ describes how the structural arrangement and magnetic microstructure appears at room temperature after the annealing under certain conditions (temperature, time), and thus this technique inspects steady states. On the other hand, NFS data are recorded in situ during dynamically changing temperature and NFS examines transient states. The use of both techniques provides complementary information. In general, they can be applied to any suitable system in which it is important to know its steady state but also transient states.
Human aldo-keto reductase 1C3 (AKR1C3) stereospecifically reduces steroids and prostaglandins and is involved in the biotransformation of xenobiotics. Its role in various cancers makes it a potential therapeutic target for the development of inhibitors. Recombinant AKR1C3 with a thrombin-cleavable N-terminal His6 tag was expressed from a pET-28(+) vector for structural studies of enzyme-inhibitor complexes. A modified in situ proteolysis approach was applied to specifically remove the His tag by thrombin cleavage during crystallization screening trials. This improved the morphology and diffraction quality of the crystals and allowed the acquisition of high-resolution diffraction data and structure solution. This approach may be generally applicable to other proteins expressed using the pET-28(+) vector.
- MeSH
- difrakce rentgenového záření metody MeSH
- histidin * genetika MeSH
- krystalizace metody MeSH
- krystalografie rentgenová metody MeSH
- lidé MeSH
- protein AKR1C3 chemie genetika metabolismus MeSH
- proteolýza MeSH
- sekvence aminokyselin MeSH
- trombin metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A sustainable way to recover phosphorus (P) in swine wastewater involves a preliminary step of P dissolution followed by the separation of particulate organic matter (OM). The next two steps are firstly the precipitation of struvite crystals done by adding a crystallization reagent (magnesia) and secondly the filtration of the crystals. To develop the process successfully at an industrial scale, the control of the mechanisms of precipitation is the key point in order to obtain high value-added products, that is, big struvite crystals easy to harvest and handle. Experiments with process parameters optimized previously in a synthetic swine wastewater were performed on real swine wastewater to assess the role of the OM on struvite crystallization. After 24 h, with a pH increase to 6.8 only, 90% of the initial P was precipitated and 60% was precipitated as struvite. 80% of the solid recovered was in the fraction > 100 µm. The other forms recovered were brushite, amorphous calcium phosphate, NaCl, KCl and OM. The influence of OM on struvite precipitation in acidified swine wastewater was negative on the reaction kinetics but positive on the size of the struvite crystals. The presence of colloidal particles increased the size of the struvite crystals but slowed down the kinetics due to the viscosity induced by the repulsive force of the colloids. The maximum size of single struvite crystals (200 µm) was observed with the presence of particulate OM.
- MeSH
- fosfáty chemie MeSH
- fosfor chemie MeSH
- hnůj MeSH
- koloidy chemie MeSH
- koncentrace vodíkových iontů MeSH
- krystalizace metody MeSH
- odpad tekutý - odstraňování MeSH
- odpadní voda chemie MeSH
- prasata MeSH
- sloučeniny hořčíku chemie MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
pH-dependent sustained-release Tulsion® microspheres bearing clarithromycin were prepared using quasi-emulsion solvent diffusion method with thermocoat L 30 D 55 as a release retardant. Both, clarithromycin and thermocoat L 30 D 55, were found to be non-hemolytic during in vitro toxicity assay against human red blood cells. Ratiometric optimization of different solvents using phase diagrams was performed on amount of good solvent, bridging liquid, dispersing liquid and poor solvent. The developed microspheres were evaluated for the recovery (67.27 ± 3.3%), average particle size (52.0 ± 0.46 μm) and encapsulation efficiency (61.0 ± 3.1%). Scanning electron microscopy and transmission electron microscopy revealed that the microspheres were smooth in surface and spherical in shape, respectively. The drug release study was conducted at different pH of GIT and it gave a pH dependent release for clarithromycin. The bioavailability study revealed increased AUC (2 fold) and half-life (1.2 fold) of microspheres as compared to plain drug. The manuscript reported the debut work on thermocoat L 30 D 55 based novel drug delivery system, the polymer is safe to be used, quasi emulsion spherical crystallization technique is a good technique to prepare microspheres, the prepared microspheres provides sustain release profile as well as targeting to colon.
- MeSH
- biologická dostupnost MeSH
- erytrocyty účinky léků MeSH
- farmaceutická chemie metody MeSH
- gastrointestinální trakt radiografie MeSH
- klarithromycin farmakokinetika MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu rattus MeSH
- krystalizace metody MeSH
- kyseliny polymethakrylové * toxicita MeSH
- léky s prodlouženým účinkem * farmakokinetika chemická syntéza chemie MeSH
- mikrosféry MeSH
- rozpouštědla chemie MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Mucoadhesive buccal films (MBFs) provide an innovative way to facilitate the efficient site-specific delivery of active compounds while simultaneously separating the lesions from the environment of the oral cavity. The structural diversity of these complex multicomponent and mostly multiphase systems as well as an experimental strategy for their structural characterization at molecular scale with atomic resolution were demonstrated using MBFs of ciclopirox olamine (CPX) in a poly(ethylene oxide) (PEO) matrix as a case study. A detailed description of each component of the CPX/PEO films was followed by an analysis of the relationships between each component and the physicochemical properties of the MBFs. Two distinct MBFs were identified by solid-state NMR spectroscopy: (i) at low API (active pharmaceutical ingredient) loading, a nanoheterogeneous solid solution of CPX molecularly dispersed in an amorphous PEO matrix was created; and (ii) at high API loading, a pseudoco-crystalline system containing CPX-2-aminoethanol nanocrystals incorporated into the interlamellar space of a crystalline PEO matrix was revealed. These structural differences were found to be closely related to the mechanical and physicochemical properties of the prepared MBFs. At low API loading, the polymer chains of PEO provided sufficient quantities of binding sites to stabilize the CPX that was molecularly dispersed in the highly amorphous semiflexible polymer matrix. Consequently, the resulting MBFs were soft, with low tensile strength, plasticity, and swelling index, supporting rapid drug release. At high CPX content, however, the active compounds and the polymer chains simultaneously cocrystallized, leaving the CPX to form nanocrystals grown directly inside the spherulites of PEO. Interfacial polymer-drug interactions were thus responsible not only for the considerably enhanced plasticity of the system but also for the exclusive crystallization of CPX in the thermodynamically most stable polymorphic form, Form I, which exhibited reduced dissolution kinetics. The bioavailability of CPX olamine formulated as PEO-based MBFs can thus be effectively controlled by inducing the complete dispersion and/or microsegregation and nanocrystallization of CPX olamine in the polymer matrix. Solid-state NMR spectroscopy is an efficient tool for exploring structure-property relationships in these complex pharmaceutical solids.
- MeSH
- adheziva chemie metabolismus MeSH
- biologická dostupnost MeSH
- ethylenoxid chemie MeSH
- farmaceutická chemie metody MeSH
- krystalizace metody MeSH
- magnetická rezonanční spektroskopie metody MeSH
- nanočástice chemie MeSH
- orální absorpce fyziologie MeSH
- polyethylenglykoly chemie metabolismus MeSH
- polymery chemie MeSH
- pyridony chemie MeSH
- rozpustnost MeSH
- ústní sliznice metabolismus MeSH
- uvolňování léčiv fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- internacionalita MeSH
- krystalizace metody MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- makromolekulární látky chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodní články MeSH
