A sustained effort to maximize the therapeutic effect of newly discovered active pharmaceutical ingredients (APIs) leads to the search for and development of advanced drug formulations. In this regard, a range of multicomponent and nanostructured systems that often combine the properties of solid and liquid materials have been developed. Besides the sophisticated supramolecular synthesis the development of these systems also requires in-depth view into their local architecture at atomic-resolution level. As these materials naturally exist at the borderline between the solid and liquid phases, the high-quality diffraction data are inherently unavailable. Therefore the structural description of these materials requires development of novel and highly efficient strategies. The aim of all this process is formulation of computation-experimental procedures allowing for precise characterization of the complex pharmaceutical systems including composite solids, nanocrystalline systems as well as partially ordered materials. In this regard, NMR crystallography belongs among the most successful approaches. In this contribution we report our recent achievements in characterizing atomic-resolution structure of complex pharmaceutical solids such as peptide derivatives of boronic acid, hybrid organic-inorganic liquisolid drug delivery systems, polymer-drug solid dispersions and mucoadhesive buccal films.

• Klíčová slova
• krystalové struktury,
• MeSH
• algináty chemie   MeSH
• Aspirin chemie   MeSH
• ciklopirox chemie   MeSH
• farmaceutická technologie klasifikace   MeSH
• krystalografie * metody   MeSH
• léčivé přípravky MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• nanomedicína dějiny   metody   MeSH
• polymery aplikace a dávkování   chemie   MeSH
• sloučeniny boru chemie   MeSH
• Publikační typ
• práce podpořená grantem MeSH

Short polypeptides with four pentad repeats, (VPGVG)(4) and (VPAVG)(4), were synthesised by manual fluorenylmethoxycarbonyl/tert-butyl (Fmoc/t-Bu) solid phase peptide synthesis using a convergent approach. In the next step, the peptides were coupled via their N-terminus with activated semi-telechelic poly(ethylene glycol) O-(N-Fmoc-2-aminoethyl)-O'-(2-carboxyethyl)undeca(ethylene glycol) (Fmoc-PEG-COOH) to yield monodisperse Fmoc-PEG-peptide diblock copolymer. Both the presence of the terminal hydrophobic Fmoc group and the hydrophilic PEG chain in the copolymers were shown to play a crucial role in their self-associative behaviour, leading to reversible formation of supramolecular thermoresponsive assemblies. The peptides and their PEG derivatives were characterised by HPLC, NMR and MALDI-TOF MS. The associative behaviour of the peptides and their PEG derivatives was studied by dynamic light scattering, MAS NMR and phase contrast microscopy. [image: see text].

• MeSH
• elastin chemie   MeSH
• financování organizované MeSH
• konformace proteinů MeSH
• magnetická rezonanční spektroskopie MeSH
• mikroskopie fázově kontrastní MeSH
• molekulární modely MeSH
• oligopeptidy chemická syntéza   chemie   MeSH
• peptidy chemie   MeSH
• polyethylenglykoly chemie   MeSH
• radiační rozptyl MeSH
• sekvence aminokyselin MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• termodynamika MeSH
• vysokoúčinná kapalinová chromatografie MeSH