Jana Kredatusová

Structural Diversity of Solid Dispersions of Acetylsalicylic Acid As Seen by Solid-State NMR

Solid dispersions of active pharmaceutical ingredients are of increasing interest due to their versatile use. In the present study polyvinylpyrrolidone (PVP), poly[N-(2-hydroxypropyl)-metacrylamide] (pHPMA), poly(2-ethyl-2-oxazoline) (PEOx), and polyethylene glycol (PEG), each in three Mw, were used to demonstrate structural diversity of solid dispersions. Acetylsalicylic acid (ASA) was used as a model drug. Four distinct types of the solid dispersions of ASA were created using a freeze-drying method: (i) crystalline solid dispersions containing nanocrystalline ASA in a crystalline PEG matrix; (ii) amorphous glass suspensions with large ASA crystallites embedded in amorphous pHPMA; (iii) solid solutions with molecularly dispersed ASA in rigid amorphous PVP; and (iv) nanoheterogeneous solid solutions/suspensions containing nanosized ASA clusters dispersed in a semiflexible matrix of PEOx. The obtained structural data confirmed that the type of solid dispersion can be primarily controlled by the chemical constitutions of the applied polymers, while the molecular weight of the polymers had no detectable impact. The molecular structure of the prepared dispersions was characterized using solid-state NMR, wide-angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC). By applying various (1)H-(13)C and (1)H-(1)H correlation experiments combined with T1((1)H) and T1ρ((1)H) relaxation data, the extent of the molecular mixing was determined over a wide range of distances, from intimate intermolecular contacts (0.1-0.5 nm) up to the phase-separated nanodomains reaching ca. 500 nm. Hydrogen-bond interactions between ASA and polymers were probed by the analysis of (13)C and (15)N CP/MAS NMR spectra combined with the measurements of (1)H-(15)N dipolar profiles. Overall potentialities and limitations of individual experimental techniques were thoroughly evaluated.

Synergistic effects in mechanical properties of PLA/PCL blends with optimized composition, processing, and morphology

Poly(lactic acid) (PLA) is a promising material for biomedical applications due to its biodegradability and high stiffness, but suffers from low toughness. We report that blending of PLA with another biodegradable polymer, poly(e-caprolactone) (PCL), can increase the impact strength above the values of the individual components, while the other important macro- and micromechanical properties remain at well-acceptable level (above the theoretical predictions based on equivalent box model). Although some previous studies indicated incompatibility of PLA and PCL polymers, we demonstrate that the melt-mixing of the polymers with optimized viscosities (PLA/PCL viscosity ratio ∼ 1), the optimized composition (PLA/PCL = 80/20 by weight), and the optimal processing (compression molding with fast cooling) leads to optimal morphology (∼0.6 μm particles of PCL in PLA matrix) and synergistic effect in the mechanical performance of the systems. In an additional set of experiments, we show that the addition of TiO2 nanoparticles slightly improves stiffness, but significantly reduces the toughness of the resulting nanocomposites. The investigated systems were characterized by electron microscopy (SEM and TEM), notched impact strength, dynamic mechanical analysis, and microindentation hardness testing.

Organic–inorganic nanocomposite films made from polyurethane dispersions and colloidal silica particles

Abstract Polyurethane/silica nanocomposites were prepared by solution blending of polyurethane water dispersion (PUD) based on polycarbonate macrodiol with colloidal silica aqueous sol LUDOX TMA. Because of mixing PUDs made from linear polyurethane with the nanofiller, only physical polymer/filler type of interface formed by hydrogen bonds was obtained. As a result the materials were possible to reuse after dissolution in acetone followed by dispersion in water. The effect of colloidal silica content on mechanical, thermal, morphological, and swelling properties of obtained films was tested by tensile test, dynamic mechanical thermal analysis, thermogravimertic analysis, scanning electron microscopy, atomic force microscopy, and swelling analyses. The nanocomposites were classified in three groups differing in the internal structure and functional properties: organic matrix filled with inorganic nanofiller (up to 10 wt% of silica), bicontinous systems (25 and 32 wt% of silica) and inorganic matrix filled with polyurethane (50 and 60 wt% of silica). Only small amount of colloidal silica (up to 10 wt%) improves thermo-mechanical properties, smoothes the materials, and suppresses extent of swelling without changing of the films transparency.

Strong synergistic effects in PLA/PCL blends: Impact of PLA matrix viscosity

Blends of two biodegradable polymers, poly(lactic acid) (PLA) and poly(ϵ-caprolactone) (PCL), with strong synergistic improvement in mechanical performance were prepared by melt-mixing using the optimized composition (80/20) and the optimized preparation procedure (a melt-mixing followed by a compression molding) according to our previous study. Three different PLA polymers were employed, whose viscosity decreased in the following order: PLC ≈ PLA1 > PLA2 > PLA3. The blends with the highest viscosity matrix (PLA1/PCL) exhibited the smallest PCL particles (d∼0.6μm), an elastic-plastic stable fracture (as determined from instrumented impact testing) and the strongest synergistic improvement in toughness (>16× with respect to pure PLA, exceeding even the toughness of pure PCL). According to the available literature, this was the highest toughness improvement in non-compatiblized PLA/PCL blends ever achieved. The decrease in the matrix viscosity resulted in an increase in the average PCL particle size and a dramatic decrease in the overall toughness: the completely stable fracture (for PLA1/PCL) changed to the stable fracture followed by unstable crack propagation (for PLA2/PCL) and finally to the completely brittle fracture (for PLA3/PCL). The stiffness of all blends remained at well acceptable level, slightly above the theoretical predictions based on the equivalent box model. Despite several previous studies, the results confirmed that PLA and PCL could behave as compatible polymers, but the final PLA/PCL toughness is extremely sensitive to the PCL particle size distribution, which is influenced by both processing conditions and PLA viscosity. PLA/PCL blends with high stiffness (due to PLA) and toughness (due to PCL) are very promising materials for medical applications, namely for the bone tissue engineering.

Temoporfin-loaded 1-tetradecanol-based thermoresponsive solid lipid nanoparticles for photodynamic therapy.

We developed fully biodegradable/metabolizable nanosystem based on polymer surfactant-stabilized thermoresponsive solid lipid nanoparticles with non-covalently bound photosensitizer temoporfin (T-SLNP) with particle size below 50nm. The efficacy of T-SLNP was compared with commercial temoporfin formulation in terms of in vitro phototoxicity in 4T1 (murine mammary carcinoma) and MDA-MB-231(human breast adenocarcinoma) cells and of in vivo anticancer effect in Nu/Nu mice bearing MDA-MB-231 tumors. In vitro study demonstrated faster accumulation kinetics in the cells for our formulation design resulting in higher phototoxicity against the tumor cells. In vivo anticancer efficacy was markedly improved by T-SLNP compared with commercial temoporfin formulation. Owing to controlled and sustained release properties, subcellular size, biocompatibility with tissue and cells, the T-SLNP nanodispersion prepared in this study represents promising drug delivery system applicable in cancer treatment.

Structural insight into the physical stability of amorphous Simvastatin dispersed in pHPMA: Enhanced dynamics and local clustering as evidenced by solid-state NMR and Raman spectroscopy

New drug formulations are sought for poorly water-soluble substances because there is a risk of compromised bioavailability if such substances are administered orally. Such active pharmaceutical ingredients can be reformulated as solid dispersions with suitable water-soluble polymers. In this contribution, formulation of a novel and physically stable dispersion of Simvastatin in poly(2-hydroxypropyl) methacrylamide (pHPMA) is demonstrated. Due to the limited water sorption of pHPMA and a high Tg, the prepared dispersion is more suited for oral administration and storage compared with neat amorphous Simvastatin. Surprisingly, the rate of global reorientation and the internal motion of Simvastatin molecules were enhanced and exhibited dynamical heterogeneities when incorporated into the pHPMA matrix. As revealed by solid-state nuclear magnetic resonance combined with Raman spectroscopy exploiting the fluorescence phenomenon the mobility of the ester and lactone components increased considerably, whereas the naphthalene ring remained rigid. Furthermore, the solid dispersion was found to be nano-heterogeneous with nanometer-sized Simvastatin domains. The presence of these clusters had no impact on the dynamics of the rigid pHPMA chains. Thus, the diffusion of Simvastatin molecules through the glassy pHPMA walls and the subsequent transformation of the clusters into larger crystallites were prevented. No crystallization was detected for more than two years.