Drug amorphisation by loading to inorganic mesoporous carriers represents an emerging area of improving the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). In this work, for the first time, a molecular-level insight into the process of API loading to mesoporous SiO2 (silica) carriers by the hot-melt impregnation method and its subsequent release during dissolution was obtained using ATR-FTIR spectroscopic imaging. A physical mixture of ibuprofen crystals and mesoporous silica particles was heated and the dynamics of melt loading into the silica pore structure was directly observed in situ by ATR-FTIR spectroscopic imaging. The loss of crystallinity, the redistribution of the API in the silica pore network and the subsequent stabilisation of the amorphous form upon cooling were proven. The API was involved in two different kinds of molecular-level interactions: API dimers in the amorphous bulk, and individual API molecules adsorbed on the silica surface. The melt-loaded silica carriers were comprehensively characterised by DSC, SEM and dissolution tests, which proved dissolution rate enhancement due to amorphisation of the API. Drug release form the hot-melt loaded mesoporous silica carriers was observed in real time and the conditions leading to local re-crystallisation of super-saturated solution of the API were identified.

• MeSH
• adsorpce MeSH
• biologická dostupnost MeSH
• chemie farmaceutická metody   MeSH
• diferenciální skenovací kalorimetrie MeSH
• ibuprofen aplikace a dávkování   chemie   MeSH
• krystalizace MeSH
• mikroskopie elektronová rastrovací MeSH
• nosiče léků chemie   MeSH
• oxid křemičitý chemie   MeSH
• poréznost MeSH
• rozpustnost MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• uvolňování léčiv MeSH
• voda chemie   MeSH
• vysoká teplota MeSH
• Publikační typ
• časopisecké články MeSH

The dissolution mechanism of a poorly aqueous soluble drug from amorphous solid dispersions was investigated using a combination of two imaging methods: attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging and magnetic resonance imaging (MRI). The rates of elementary processes such as water penetration, polymer swelling, growth and erosion of gel layer, and the diffusion, release and in some cases precipitation of drug were evaluated by image analysis. The results from the imaging methods were compared with drug release profiles obtained by classical dissolution tests. The study was conducted using three polymeric excipients (soluplus, polyvinylpyrrolidone - PVP K30, hydroxypropylmethyl cellulose - HPMC 100M) alone and in combination with a poorly soluble drug, aprepitant. The imaging methods were complementary: ATR-FTIR imaging enabled a qualitative observation of all three components during the dissolution experiments, water, polymer and drug, including identifying structural changes from the amorphous form of drug to the crystalline form. The comparison of quantitative MRI data with drug release profiles enabled the different processes during dissolution to be established and the rate-limiting step to be identified, which - for the drug-polymer combinations investigated in this work - was the drug diffusion through the gel layer rather than water penetration into the tablet.

• MeSH
• časové faktory MeSH
• magnetická rezonanční tomografie * přístrojové vybavení   MeSH
• molekulární struktura MeSH
• morfoliny chemie   MeSH
• polymery chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací přístrojové vybavení   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The objective of this study was to investigate the effect of different polymeric carriers in solid dispersions with an active pharmaceutical ingredient (API) on their water vapour sorption equilibria and the influence of the API-polymer interactions on the dissolution rate of the API. X-ray diffraction, scanning electron microscopy (SEM), moisture sorption analysis, infrared (IR) spectroscopy and dissolution tests were performed on various API-polymer systems (Valsartan as API with Soluplus, PVP and Eudragit polymers) after production of amorphous solid dispersions by spray drying. The interactions between the API and polymer molecules caused the water sorption isotherms of solid dispersions to deviate from those of ideal mixtures. The moisture sorption isotherms were lower in comparison with the isotherms of physical mixtures in all combinations with Soluplus and PVP. In contrast, the moisture sorption isotherms of solid dispersions containing Eudragit were significantly higher than the corresponding physical mixtures. The nature of the API-polymer interaction was explained by shifts in the characteristic bands of the IR spectra of the solid dispersions compared to the pure components. A correlation between the dissolution rate and the water sorption properties of the API-polymer systems has been established.

• MeSH
• adsorpce MeSH
• chemické modely MeSH
• farmaceutická technologie metody   MeSH
• kinetika MeSH
• krystalografie rentgenová MeSH
• kyseliny polymethakrylové chemie   MeSH
• mikroskopie elektronová rastrovací MeSH
• polyethylenglykoly chemie   MeSH
• polymery chemie   MeSH
• polyvinyly chemie   MeSH
• povidon chemie   MeSH
• rozpustnost MeSH
• tetrazoly chemie   MeSH
• valin analogy a deriváty   chemie   MeSH
• voda chemie   MeSH
• vodíková vazba MeSH
• volatilizace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH