Chemico-calorimetric analysis of amorphous granules manufactured via continuous granulation process

The current study explores the first case of the implementation of solution calorimetry (SolCal) in order to determine the amorphous content of crystalline benzoyl-methoxy-methylindol-acetic acid (BMA)—a model poorly soluble drug, in the amorphous granules prepared via single-step continuous twin-screw dry granulations (TSG). Amorphous magnesium aluminometasilicate (Neusilin®) (US2) was used as a novel inorganic carrier via a TwinLab 10 mm twin-screw extruder. The BMA/US2 blends were processed at 180 °C and varying drug: carrier ratios of 1:4, 1:2.5 and 1:1 (w/w). Physico-chemical characterisation conducted via SEM, DSC and XRPD showed amorphous state of the drug in all granulated formulations. Reverse optical microscopy revealed a meso-porous structure of US2 in which the drug particles are adsorbed and/or entrapped within the porous network of the carrier. This phenomenon can be the underlying reason for the increase of the amorphous content in the extruded granules. Solution calorimetry (SolCal) study revealed amorphous content of the drug in all formulations quite precisely, whereas the dynamic vapour sorption (DVS) analysis complemented the results from SolCal. Furthermore, an attempt has been made for the first time to interrelate the findings from the SolCal to that of the release of the drug from the amorphous granules. It can be concluded that SolCal can be used as a novel technique to precisely quantify and interrelate the amorphous content to its physico-chemical performances such as drug release from the granulated formulations processed via TS

Drop-on-powder 3d printing of tablets with an anti-cancer drug, 5-fluorouracil

This study reports the first case of an innovative drop-on-powder (DoP) three-dimensional (3D) printing technology to produce oral tablets (diameters of 10 mm and 13 mm) loaded with an anticancer model drug, 5-fluorouracil (FLU). For this study, a composition of the powder carrier containing CaSO4 hydrates, vinyl polymer, and carbohydrate was used as the matrix former, whereas 2-pyrrolidone with a viscosity like water was used as a binding liquid or inkjet ink. All tablets were printed using a commercial ZCorp 3D printer with modification. The resultant tablets were subject to coating with various polymeric solutions containing the drug. The composition of the polymeric solutions was adjusted at drug: polymer(s) 1:1 (w/w) ratio. Either Soluplus® (SOL) alone or in combination with polyethylene glycol (PEG) was used to develop the coating solution of 2.5% (w/v) concentration. The particle size analysis, flow test, and particle morphology studies revealed mono-modal narrow size distribution, good flow properties, and porous loosely bound texture (of the tablets), respectively. Moreover, the advanced application of the fluorescence microscopy showed a homogenous distribution of the drug throughout the surface of the 3D printed tablets. The in vitro dissolution studies showed that the tablet compositions, dimensions, and the coating solution compositions influenced the release of the drug from the tablets. It can be concluded that our innovative DoP 3D printing technology can be used to fabricate personalized dosage forms containing optimized drug content with high accuracy and shape fidelity. This is particularly suitable for those drugs that are highly unstable in thermal processing and cannot withstand the heat treatment, such as in fused deposition modeling (FDM) 3D printing

Effect of melt extrudability and melt binding efficiency of polyvinyl caprolactam polyvinyl acetate polyethylene glycol graft copolymer (Soluplus®) on release pattern of hydrophilic and high dose drugs

The present study explores the effect of melt binding of Soluplus® on in vitro release profiles of two hydrophilic drugs, metformin hydrochloride, and paracetamol. The melt viscosities of bulk polymer and physical mixtures with different concentrations of selected APIs were analyzed by using a rheometer. The rheological evaluation revealed both the suitable temperature range for melt extrusion process and drug-polymer extrudability. The effect of formulation and processing parameters (e.g. polymer/drug ratio, temperature, screw speed) on extrudability were evaluated in terms of torque and residence time analysis. The extrudates obtained via hot melt extrusion (HME) processing exhibited good flow and compressibility. Differential scanning calorimetry (DSC) and X-ray diffraction studies examined the change in glass transition temperature (Tg) and crystalline pattern of extruded formulations where all extruded formulations seemed to have retained their crystallinity. The thermogravimetric analysis determined the thermal stability (weight loss) as a function of operating temperature whereas scanning electron microscopy (SEM) showed agglomerated microstructure and rough surface with a porous network and void spaces. The tablets obtained after compression of milled extrudates showed excellent hardness with robust tablet characteristics. The in vitro release studies of individual batches performed in various USP recommended dissolution media (for paracetamol) showed the pH-independent release of the hydrophilic drugs from the polymer matrices

Performance of Kaolin Clay on hot-mix asphalt properties

Kaolin clay is a waste product with numerous applications in construction. This study explored the addition effect of kaolin clay on the properties of hot-mix asphalt. Four replacement levels of kaolin clay were considered by weight of binder, i.e., 2%, 4%, 6%, and 8%. The performance of kaolin clay on the hot-mix asphalt was evaluated through a Marshall stability and flow test, including stiffness, density, voids in total mix, and voids in filled with asphalt. Test results showed that kaolin clay can be satisfactorily used as filler replacement material to increase the asphalt mixture properties. Generally, asphaltic concrete with 2% kaolin clay replacement level exhibits excellent performance with good stability and stiffness

Characterization of magnetically triggerable millirobots for on demand drug delivery using a brightfield microscopy metrology system

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Development of a Simple Mechanical Screening Method for Predicting the Feedability of a Pharmaceutical FDM 3D Printing Filament

Purpose: The filament-based feeding mechanism employed by the majority of fused deposition modelling (FDM) 3D printers dictates that the materials must have very specific mechanical characteristics. Without a suitable mechanical profile, the filament can cause blockages in the printer. The purpose of this study was to develop a method to screen the mechanical properties of pharmaceutically-relevant, hot-melt extruded filaments to predetermine their suitability for FDM. Methods: A texture analyzer was used to simulate the forces a filament is subjected to inside the printer. The texture analyzer produced a force-distance curve referred to as the flexibility profile. Principal Component Analysis and Correlation Analysis statistical methods were then used to compare the flexibility profiles of commercial filaments to in-house made filaments. Results: Principal component analysis showed clearly separated clustering of filaments that suffer from mechanical defects versus filaments which are suitable for printing. Correlation scores likewise showed significantly greater values with feedable filaments than their mechanically deficient counterparts. Conclusion: The screening method developed in this study showed, with statistical significance and reproducibility, the ability to predetermine the feedability of extruded filaments into an FDM printer

Towards analytical typologies of plot systems: quantitative profile of five European cities

The importance of the plot (also referred to as ‘property’) as one of the fundamental elements of urban form is well recognized within the field of urban morphology. Despite the fact that it is often described as the basic element in the pattern of land divisions, which are essential as organizational frameworks for urban form, studies offering comprehensive descriptions and classifications of plot systems are quite scant. The aim of the paper is to introduce a classification of plot systems into typologies based on five European cities, in order to distinguish particular spatial differences and similarities in terms of their plot structure. The proposed typologies are developed using unsupervised k-means cluster analysis based on numeric attributes derived from central theories in urban morphology. The introduced typologies are essentially configurational, allowing collective systematic properties of plot systems to be captured. Numeric attributes include plot differentiation (or plot size), plot frontage and compactness ratio, corresponding to essential qualities of plot systems such as the capacity to carry differences in space, the ability to operate as interface between street and building and providing a framework for evolution of built form over time. All three attributes are translated into configurational measures in order to capture the context of the plot system, rather than the parameters of individual plots. The combination of these deductively defined variables with algorithmically defined classification methods results in seven plot types that can be used to scale up traditional urban morphological analysis to whole city regions and conduct substantial comparison of patterns within, but also between these regions. Further, it also makes it possible to describe commonly recognized plot patterns and discover new ones

Development and optimisation of spironolactone nanoparticles for enhanced dissolution rates and stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability

A review of the corrosion behavior of metallic heritage structures and artifacts

Awareness about restoring and preserving historically important structures and artifacts is gradually growing in many parts of the world. These artifacts and structures represent the culture, tradition and past of a nation. They are often also a source of national income through tourist activities. Besides masonry and wood work, metallic forms and relics are a vital part of the heritage which needs to be conserved. Certain metals have been used significantly throughout history in the creation of objects and structures. However, metals are prone to decay over time, particularly decay through corrosion. The basic mechanisms of metal corrosion, the various types of corrosion and existing remedial solutions are reviewed in this paper. The most significant factor affecting metal corrosion was found to be the surrounding environment, especially in marine areas. Different remedial measures can be implemented on corroded metals according to their specific properties. Recommendations for further study are offered at the end of the paper