Spray drying and hot-melt extrusion are among the most prevalent preparation techniques used in the pharmaceutical industry to produce amorphous solid dispersions (ASDs). This study advances previous research by integrating sample production, comprehensive analytical characterization, intrinsic dissolution rate measurements, and assessments of the behavior of ASDs under elevated temperature and humidity conditions. The study focuses on indomethacin, a widely used model for poorly soluble drugs, processed with PVP K30 or HPMC E5, both commonly used polymers. The findings demonstrate that hot-melt extruded samples exhibit superior stability against recrystallization, whereas spray dried samples achieve higher intrinsic dissolution rates. Furthermore, PVP K30 significantly outperforms HPMC E5 in the co-processing of indomethacin, enhancing both the intrinsic dissolution rate and the stability.
- MeSH
- deriváty hypromelózy chemie MeSH
- farmaceutická chemie metody MeSH
- indomethacin * chemie MeSH
- krystalizace * MeSH
- povidon chemie MeSH
- příprava léků metody MeSH
- rozpustnost * MeSH
- sprejové sušení * MeSH
- stabilita léku * MeSH
- technologie extruze tavenin * metody MeSH
- uvolňování léčiv MeSH
- vlhkost MeSH
- vysoká teplota MeSH
- vysoušení metody MeSH
- Publikační typ
- časopisecké články MeSH
The integration of 3D printing into the pharmaceutical sciences opens new possibilities for personalized medicine. Poly(lactide) (PLA), a biodegradable and biocompatible polymer, is highly suitable for biomedical applications, particularly in the context of 3D printing. However, its processability often requires the addition of plasticizers. This study investigates the use of phase diagram modeling as a tool to guide the rational selection of plasticizers and to assess their impact on the thermodynamic and kinetic stability of PLA-based amorphous solid dispersions (ASDs) containing active pharmaceutical ingredients (APIs). Thermodynamic stability against API recrystallization was predicted based on the API solubility in PLA and Plasticizer-PLA carriers using the Conductor-like Screening Model for Real Solvents (COSMO-RS), while the kinetic stability of the ASDs was evaluated by modeling the glass transition temperatures of the mixtures. Two APIs, indomethacin (IND) and naproxen (NAP), with differing glass-forming abilities (i.e., recrystallization tendencies), and three plasticizers, triacetin (TA), triethyl citrate (TEC), and poly(L-lactide-co-caprolactone) (PLCL), were selected for investigation. The physical stability of ASD formulations containing 9 wt% API and plasticizer to PLA in two ratios, 10:81 and 20:71 w/w %, was monitored over time using differential scanning calorimetry and X-ray powder diffraction and compared with phase diagram predictions. All formulations were predicted to be thermodynamically unstable; however, those containing no plasticizer or with TEC and TA at 10 wt% were predicted to exhibit some degree of kinetic stability. Long-term physical studies corroborated these predictions. The correlation between the predicted phase behavior and long-term physical stability highlights the potential of phase diagram modeling as a tool for the rational design of ASDs in pharmaceutical 3D printing.
- MeSH
- 3D tisk * MeSH
- citráty chemie MeSH
- diferenciální skenovací kalorimetrie metody MeSH
- farmaceutická chemie metody MeSH
- farmaceutická technologie metody MeSH
- indomethacin * chemie MeSH
- krystalizace MeSH
- naproxen chemie MeSH
- polyestery * chemie MeSH
- rozpouštědla chemie MeSH
- rozpustnost * MeSH
- stabilita léku MeSH
- termodynamika MeSH
- tranzitní teplota MeSH
- triacetin chemie MeSH
- změkčovadla * chemie MeSH
- Publikační typ
- časopisecké články MeSH
Nanocrystalline cerium dioxide is able to protect living cells from oxidative stress under the influence of various stress factors, in particular under the one of low temperatures. This study investigates the phase-structural transformations in aqueous solutions containing CeO2 nanoparticles (NPs) and their impact on the cryopreservation process. Differential scanning calorimetry and thermomechanical analysis were used to analyse the phase transitions in aqueous suspensions of CeO2 NPs and aqueous solutions of the cryoprotectant dimethyl sulfoxide (Me2SO) with CeO2 NPs. Various concentrations of CeO2 NPs were tested to observe their effects on the crystallization and melting behaviours. The addition of CeO2 NPs significantly altered the temperatures and enthalpies of melting and crystallization in water. Low concentrations of CeO2 NPs promoted crystallization, while higher concentrations inhibited it, reducing supercooling and recrystallization during thawing. In Me2SO solutions, CeO2 NPs raised the glass transition temperature and affected the recrystallization process, with higher concentrations leading to more pronounced vitrification and reduced recrystallization. We also investigated the regularities of the effect of CeO2 NPs on phase transitions in combined cryoprotective media with Ham's F12, fetal bovine serum and Me2SO, which can be used in future to design the cryopreservation protocols. In the complex media, CeO2 NPs decreased the metastability and altered eutectic crystallization patterns, indicating potential cryoprotective effects. In conclusion, CeO2 NPs modulate the thermophysical properties of cryoprotective solutions, enhancing vitrification and reducing recrystallization, which could improve cryopreservation efficiency. Optimizing NP concentrations is crucial for practical applications in cryopreservation.
- MeSH
- cer * chemie farmakologie MeSH
- diferenciální skenovací kalorimetrie * MeSH
- dimethylsulfoxid * chemie MeSH
- kryoprezervace * metody MeSH
- kryoprotektivní látky * chemie farmakologie MeSH
- krystalizace * MeSH
- nanočástice * chemie MeSH
- tranzitní teplota MeSH
- vitrifikace * účinky léků MeSH
- změna skupenství * MeSH
- Publikační typ
- časopisecké články MeSH
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.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
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 aim of this study was to improve rivaroxaban water-solubility by cocrystal preparation and to understand this process. The screening with water-soluble coformers was performed via both mechanochemical and solution-mediated techniques. Two cocrystals of rivaroxaban with malonic acid and oxalic acid were prepared, and the structure of the cocrystal with oxalic acid was solved. Both cocrystals exhibit improved dissolution properties. The mechanism of the supersaturation maintenance was studied by in-situ Raman spectroscopy. The transformation into rivaroxaban dihydrate was identified as the critical step in the improved dissolution properties of both cocrystals. Moreover, the transformation kinetics and solubilization effects of the coformers were identified as responsible for the differences in the dissolution behavior of the cocrystals. In-vivo experiments proved that the use of cocrystal instead of form I of free API helped to increase the bioavailability ofrivaroxaban.
Influenza viruses can cause severe respiratory infections in humans, leading to nearly half a million deaths worldwide each year. Improved antiviral drugs are needed to address the threat of development of novel pandemic strains. Current therapeutic interventions target three key proteins in the viral life cycle: neuraminidase, the M2 channel and RNA-dependent-RNA polymerase. Protein-protein interactions between influenza polymerase subunits are potential new targets for drug development. Using a newly developed assay based on AlphaScreen technology, we screened a peptide panel for protein-protein interaction inhibitors to identify a minimal PB1 subunit-derived peptide that retains high inhibition potential and can be further modified. Here, we present an X-ray structure of the resulting decapeptide bound to the C-terminal domain of PA polymerase subunit from pandemic isolate A/California/07/2009 H1N1 at 1.6 Å resolution and discuss its implications for the design of specific, potent influenza polymerase inhibitors.
- MeSH
- antivirové látky farmakologie MeSH
- interakční proteinové domény a motivy účinky léků fyziologie MeSH
- krystalizace MeSH
- lidé MeSH
- RNA-dependentní RNA-polymerasa chemie metabolismus MeSH
- vazba proteinů MeSH
- virové proteiny antagonisté a inhibitory chemie metabolismus MeSH
- virus chřipky A, podtyp H1N1 účinky léků enzymologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Iron-based nanomaterials have high technological impacts on various pro-environmental applications, including wastewater treatment using the co-precipitation method. The purpose of this research was to identify the changes of iron nanomaterial's structure caused by the presence of selenium, a typical water contaminant, which might affect the removal when the iron co-precipitation method is used. Therefore, we have investigated the maturation of co-precipitated nanosized ferric oxyhydroxides under alkaline conditions and their thermal transformation into hematite in the presence of selenite and selenate with high concentrations. Since the association of selenium with precipitates surfaces has been proven to be weak, the mineralogy of the system was affected insignificantly, and the goethite was identified as an only ferric phase in all treatments. However, the morphology and the crystallinity of ferric oxyhydroxides was slightly altered. Selenium affected the structural order of precipitates, especially at the initial phase of co-precipitation. Still, the crystal integrity and homogeneity increased with time almost constantly, regardless of the treatment. The thermal transformation into well crystalized hematite was more pronounced in the presence of selenite, while selenate-treated and selenium-free samples indicated the presence of highly disordered fraction. This highlights that the aftermath of selenium release does not result in destabilization of ferric phases; however, since weak interactions of selenium are dominant at alkaline conditions with goethite's surfaces, it still poses a high risk for the environment. The findings of this study should be applicable in waters affected by mining and metallurgical operations.
- MeSH
- alkálie chemie MeSH
- chemická precipitace MeSH
- krystalizace MeSH
- kyselina seleničitá chemie MeSH
- kyselina selenová chemie MeSH
- minerály chemie MeSH
- sloučeniny železa chemie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- spektroskopie Mossbauerova MeSH
- teplota MeSH
- železité sloučeniny chemie MeSH
- železo chemie MeSH
- Publikační typ
- časopisecké články MeSH
Yeast glucan particles are porous polysaccharide cell walls extracted from Saccharomyces cerevisiae. Being mildly immunogenic, they are efficiently phagocytosed and have therefore been proposed as possible vehicles for drug delivery. Using curcumin as a model poorly water-soluble drug, a systematic comparison of three different physical loading methods - incipient wetness impregnation, slurry evaporation, and spray drying - was carried out and their influence on the particle morphology, encapsulation efficiency, amorphous drug content and release kinetics was evaluated. It was found that yeast glucan particles can contain up to 30% wt. of curcumin in the amorphous form when prepared by slurry evaporation. The dissolution of curcumin from glucan particles lead to a supersaturated solution in asimilar way as amorphous solid dispersions do, despite the fact that glucan particles themselves do not dissolve. Bi-phasic dissolution tests revealed up to 4-fold acceleration of curcumin dissolution rate from amorphous glucan particles compared to its crystalline form. Crucially, glucan particles were shown to retain the ability to be recognised and phagocytosed even after drug encapsulation.
- MeSH
- beta-glukany chemie MeSH
- farmaceutická chemie metody MeSH
- kinetika MeSH
- krystalizace MeSH
- kurkumin aplikace a dávkování chemie MeSH
- lékové transportní systémy * MeSH
- nosiče léků chemie MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- uvolňování léčiv MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
