CdS-Decorated Porous Anodic SnOx Photoanodes with Enhanced Performance under Visible Light.

Electrochemically generated nanoporous tin oxide films have already been studied as photoanodes in photoelectrochemical water splitting systems. However, up to now, the most significant drawback of such materials was their relatively wide band gap (ca. 3.0 eV), which limits their effective performance in the UV light range. Therefore, here, we present for the first time an effective strategy for sensitization of porous anodic SnOx films with another narrow band gap semiconductor. Nanoporous tin oxide layers were obtained by simple one-step anodic oxidation of metallic Sn in 1 M NaOH followed by further surface decoration with CdS by the successive ionic layer adsorption and reaction (SILAR) method. It was found that the nanoporous morphology of as-anodized SnOx is still preserved after CdS deposition. Such SnOx/CdS photoanodes exhibited enhanced photoelectrochemical activity in the visible range compared to unmodified SnOx. However, the thermal treatment at 200 °C before the SILAR process was found to be a key factor responsible for the optimal photoresponse of the material.

How Does the Addition of Kollidon®VA64 Inhibit the Recrystallization and Improve Ezetimibe Dissolution from Amorphous Solid Dispersions?

Amorphization serves as a strategy for the improvement of poor dissolution characteristics of many drug compounds. However, in many formulations the content of polymeric stabilizer is high, which is undesirable from the perspective of future applications. Thus, studying the composition-dependent stability of amorphous solid dispersions seems to be demanded. In this paper, we describe the amorphization of ezetimibe, a lipid-lowering drug, in the spray drying process and investigate the effect of polyvinylpyrrolidone-co-poly(vinyl acetate) (PVP/VA) content on the physical stability and dissolution characteristics of the drug. Fully amorphous systems were obtained when the concentration of the polymer in solid dispersion was as low as 20%. The amorphization led to the dissolution enhancement by even 70%, with a noticeable sudden increase at around 40% of PVP/VA content and very small variations for systems having 66-90% PVP/VA. It was also correlated to wettability characteristics of solid dispersions, which may suggest that in the vicinity of 40% of the polymer content, the behavior of the system becomes independent of the PVP/VA content.

How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements. Differential scanning calorimetry was applied to assess thermal properties, while X-ray powder diffractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release.

Tabletting solid dispersions of bicalutamide prepared using ball-milling or supercritical carbon dioxide: the interrelationship between phase transition and in-vitro dissolution.

The studies were aimed at formulating tablets containing bicalutamide-PVP K-29/32 solid dispersions and accessing the interrelationships between the properties of obtained binary systems in the form of powder and compacts. The effect of the compression of the solid dispersions obtained by either milling or using the supercritical fluid method on the dissolution and phase transition of the drug was investigated. Mechanical stress induced the amorphization of the drug, while the treatment with supercritical carbon dioxide did not cause any phase transition as confirmed by X-ray diffractometry. Co-processing of the drug substance with the carrier resulted in even a 10-fold improvement of the bicalutamide dissolution from the solid dispersions. The release of the drug from tablets was lower than from the corresponding powder system.

Compression-Induced Phase Transitions of Bicalutamide.

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

Hierarchical Nanoporous Sn/SnOx Systems Obtained by Anodic Oxidation of Electrochemically Deposited Sn Nanofoams.

A simple two-step electrochemical method for the fabrication of a new type of hierarchical Sn/SnOx micro/nanostructures is proposed for the very first time. Firstly, porous metallic Sn foams are grown on Sn foil via hydrogen bubble-assisted electrodeposition from an acidulated tin chloride electrolyte. As-obtained metallic foams consist of randomly distributed dendrites grown uniformly on the entire metal surface. The estimated value of pore diameter near the surface is ~35 µm, while voids with a diameter of ~15 µm appear in a deeper part of the deposit. Secondly, a layer of amorphous nanoporous tin oxide (with a pore diameter of ~60 nm) is generated on the metal surface by its anodic oxidation in an alkaline electrolyte (1 M NaOH) at the potential of 4 V for various durations. It is confirmed that if only optimal conditions are applied, the dendritic morphology of the metal foam does not change significantly, and an open-porous structure is still preserved after anodization. Such kinds of hierarchical nanoporous Sn/SnOx systems are superhydrophilic, contrary to those obtained by thermal oxidation of metal foams which are hydrophobic. Finally, the photoelectrochemical activity of the nanostructured metal/metal oxide electrodes is also presented.

Speed it up, slow it down An issue of bicalutamide release from 3D printed tablets.

The article describes the preparation and characterization of 3D-printed tablets with bicalutamide obtained using two-material co-extrusion-based fused deposition modeling (FDM). This method is a modification of typical two-material FDM where separate nozzles are used to print from two filaments. In this work we used a ZMorph® 3D printer with DualPro printhead which allows us to co-extrude two filaments through a single nozzle. This approach gives the opportunity to modify tablet properties in a wide range, especially the dissolution rate, by producing dosage forms with a complex design. The great advantage of this method is that switching between immediate dosage form and controlled release does not require any change in the 3D-printer set-up. We checked the accuracy of co-extrusion printing simply by weighing the amounts of soluble and insoluble material in the printed object as well as calculating the volumes of the printed objects from micro computed tomography (µ-CT) images. We printed several tablets with a different design including simple one-material tablets, two- and three-compartment tablets with various internal structure and composition of the printing path. The dissolution tests were conducted in sink and non-sink conditions. We obtained tablets with desired bicalutamide dissolution profiles, i.e. immediate, controlled, and combined. The formation of spatial matrix slows down the dissolution in controlled and combined release bicalutamide tablets what was confirmed by µ-CT analysis before and after dissolution.

The Self-Assembly Phenomenon of Poloxamers and Its Effect on the Dissolution of a Poorly Soluble Drug from Solid Dispersions Obtained by Solvent Methods.

The self-assembly phenomenon of amphiphiles has attracted particular attention in recent years due to its wide range of applications. The formation of nanoassemblies able to solubilize sparingly water-soluble drugs was found to be a strategy to solve the problem of poor solubility of active pharmaceutical ingredients. Binary and ternary solid dispersions containing Biopharmaceutics Classification System (BCS) class II drug bicalutamide and either Poloxamer®188 or Poloxamer®407 as the surface active agents were obtained by either spray drying or solvent evaporation under reduced pressure. Both processes led to morphological changes and a reduction of particle size, as confirmed by scanning electron microscopy and laser diffraction measurements. The increase in powder wettability was confirmed by means of contact angle measurements. The effect of an alteration of the crystal structure was followed by powder X-ray diffractometry while thermal properties were determined using differential scanning calorimetry. Interestingly, bicalutamide exhibited a polymorph transition after spray drying with the poloxamer and polyvinylpyrrolidone (PVP), while the poloxamer underwent partial amorphization. Moreover, due to the surface activity of the carrier, the solid dispersions formed nanoaggregates in water, as confirmed using dynamic light scattering measurements. The aggregates measuring 200⁻300 nm in diameter were able to solubilize bicalutamide inside the hydrophobic inner parts. The self-assembly of binary systems was found to improve the amount of dissolved bicalutamide by 4- to 8-fold in comparison to untreated drug. The improvement in drug dissolution was correlated with the solubilization of poorly soluble molecules by macromolecules, as assessed using emission spectroscopy.

Molecular Disorder of Bicalutamide-Amorphous Solid Dispersions Obtained by Solvent Methods.

The effect of solvent removal techniques on phase transition, physical stability and dissolution of bicalutamide from solid dispersions containing polyvinylpyrrolidone (PVP) as a carrier was investigated. A spray dryer and a rotavapor were applied to obtain binary systems containing either 50% or 66% of the drug. Applied techniques led to the formation of amorphous solid dispersions as confirmed by X-ray powder diffractometry and differential scanning calorimetry. Moreover, solid⁻solid transition from polymorphic form I to form II was observed for bicalutamide spray dried without a carrier. The presence of intermolecular interactions between the drug and polymer molecules, which provides the stabilization of molecularly disordered bicalutamide, was analyzed using infrared spectroscopy. Spectral changes within the region characteristic for amide vibrations suggested that the amide form of crystalline bicalutamide was replaced by a less stable imidic one, characteristic of an amorphous drug. Applied processes also resulted in changes of particle geometry and size as confirmed by scanning electron microscopy and laser diffraction measurements, however they did not affect the dissolution significantly as confirmed by intrinsic dissolution study. The enhancement of apparent solubility and dissolution were assigned mostly to the loss of molecular arrangement by drug molecules. Performed statistical analysis indicated that the presence of PVP reduces the mean dissolution time and improve the dissolution efficiency. Although the dissolution was equally affected by both applied methods of solid dispersion manufacturing, spray drying provides better control of particle size and morphology as well as a lower tendency for recrystallization of amorphous solid dispersions.

3D printing of tablets containing amorphous aripiprazole by filaments co-extrusion.

Three-dimensional printing is one of the fastest developing technology within pharmaceutical field. With many advantages this method can be found as a new dosage form manufacturing technique, however low printing efficiency stays as one of the major limitations. Therefore, the preparation of filaments as a feedstock and printing of the final dosage forms in pharmacies may by the direction of development for this method. Thus, simple dosage and dissolution profile modification seems to be essential. This can be done in simple way by addition drug-free filament during printing process. In this work the influence of dual co-extrusion process on the properties of 3D-printed tablets with aripiprazole was evaluated. A ZMorph® 3D printer equipped with DualPro extruder was employed to produce tablets made from Kollicoat® IR aripiprazole-loaded filament and commercially available PLA filament used to modify the release profile. Optical and polarized light microscopy were utilized to evaluate structure of printed objects and X-ray diffraction studies were performed to determine crystallinity of aripiprazole within filament and tablets. Fast dissolution of aripiprazole resulted from its amorphization while prolonged drug release was a result of co-extrusion with PLA filament. Importantly, the drug remained crystalline within the filament and phase transition into disordered system appeared during printing of tablets. Given the high stability of crystalline materials such feature is especially beneficial for long-term storage of feedstock filament.

Enhanced dissolution of solid dispersions containing bicalutamide subjected to mechanical stress.

The anticancer drug bicalutamide was co-milled with either Macrogol 6000 or Poloxamer 407, and the physicochemical parameters that drive the phase transition of binary systems and influence the dissolution modification of bicalutamide were studied. Milled binary systems with reduced particle size were assessed by scanning electron microscopy and laser diffraction measurements. The results of thermal analysis supported by X-ray diffractometry confirmed the reduction of the crystallinity of bicalutamide co-milled with Macrogol 6000. Infrared spectroscopy was used to determine the molecular structure of the samples and indicated weak interactions between drug and polymer molecules. Two mechanisms were identified and were involved in up to 11-fold enhanced dissolution. The first one was based on improved wettability due to a decreased contact angle in samples containing Macrogol 6000. The second one relied on the solubilization of bicalutamide within nanoaggregates formed by Poloxamer 407 that resulted from its surface activity. This finding was confirmed with fluorescence spectroscopy, dynamic light scattering and cryogenic transmission electron microscopy assays. Given the dissolution rate-limited absorption combined with the reduced bioavailability of bicalutamide as a BCS class II drug, the assessment of the mechanisms driving the increase in drug dissolution is of particular importance in drug development.