Modeling of Styl'One Evolution Correction Factors for Multicomponent Mixtures Scaling-up to Roller Compaction.

Roll compaction (RC) is a cost-effective dry granulation method, widely implemented in the pharmaceutical industry. In early formulation development however, when the material availability is limited, being able to predict the most important parameters in RC, like gap width and specific compaction force (SCF), to obtain a target ribbon solid fraction (SF) would significantly improve the formulation development efficiency as it would avoid the need of performing experiments on the roller compactor itself. However, at the present state of things, experiments on RC mechanical simulators present an overestimation of the target SF, when compared to roller compactor SF values. Although numerous correction approaches have been developed to improve the predictive performance of different mathematical models applied to the simulation experimental results, no study has collected a database wide enough to demonstrate the validity of a correction factor that allows to accurately simulate the compaction behavior of multicomponent mixtures. Here, 25 different formulations at 40 % drug load are compacted at different SCFs, both on a RC mimicking device (Styl'One Evolution) and on an actual roller compactor (Gerteis Mini-Pactor): following a similar approach as Reimer et al. and implementing a simplified version of the Johanson's mathematical model, 4 different correction factors are calculated, depending on how their material properties and pressure dependencies are considered. In conclusion, one correction factor is identified as the optimal trade-off between the SF prediction accuracy on the Gerteis Mini-Pactor and its applicability to a wide range of formulations, as it is independent of the material properties. This finding is particularly relevant when applied to scale-up to this specific roller compactor or early development processes of new formulations that have not been mechanically characterized yet.

Recent advances in dental zirconia: 15 years of material and processing evolution.

OBJECTIVES: The objective was to discuss the research on zirconia published in the past 15 years to help the dental materials community understand the key properties of the types of zirconia and their clinical applications. METHODS: A literature search was performed in May/2023 using Web of Science Core Collection with the term "dental zirconia". The search returned 5102 articles, which were categorized into 31 groups according to the research topic. RESULTS: The current approach to improving the translucency of zirconia is to decrease the alumina content while increasing the yttria content. The resulting materials (4Y-, 5Y-, and above 5 mol% PSZs) may contain more than 50% of cubic phase, with a decrease in mechanical properties. The market trend for zirconia is the production of CAD/CAM disks containing more fracture resistant 3Y-TZP at the bottom layers and more translucent 5Y-PSZ at the top. Although flaws located between layers in multilayered blocks might represent a problem, newer generations of zirconia layered blocks appear to have solved this problem with novel powder compaction technology. Significant advancements in zirconia processing technologies have been made, but there is still plenty of room for improvement, especially in the fields of high-speed sintering and additive manufacturing. SIGNIFICANCE: The wide range of zirconia materials currently available in the market may cause confusion in materials selection. It is therefore imperative for dental clinicians and laboratory technicians to get the needed knowledge on zirconia material science, to follow manufacturers' instructions, and to optimize the design of the prosthetic restoration with a good understanding where to reinforce the structure with a tough and strong zirconia.

Effect of magnesium stearate solid lipid nanoparticles as a lubricant on the properties of tablets by direct compression.

This study discusses the lubricant properties of magnesium stearate solid lipid nanoparticles (MgSt-SLN) and their effect on the tabletability, mechanical properties, disintegration, and acetaminophen-model dissolution time of microcrystalline cellulose (MCC) tablets prepared by direct compression. The behavior of MgSt-SLN was compared to reference material (RM) to identify advantages and drawbacks. The nanoprecipitation/ion exchange method was employed to prepare the MgSt-SLN. Particle size, zeta potential, specific surface area, morphology, and true density were measured to characterize the nanosystem. The MgSt-SLN particle sizes obtained were 240 ± 5 nm with a specific surface area of 12.2 m2/g. The MCC tablets with MgSt-SLN presented a reduction greater than 20 % in their ejection force, good tabletability, higher tensile strength, lower disintegration delay, and marked differences in acetaminophen dissolution when compared to the RM. The reduced particle size of the magnesium stearate seems to offer a promising technological advantage as an efficient lubricant process that does not affect the properties of tablets.

Mechanical and radiation shielding characterization of W-based alloys for advanced nuclear unit.

The paper aims to investigate the mechanical and radiation shielding properties of two tungsten-based alloys manufactured by powder technology; their features when compared with two standard stainless steel grades for advanced nuclear applications. Multiple measurements were performed to characterize the alloys' structural and mechanical properties. XRD analysis and average surface roughness measurements showed the crystalline and morphological structure of the alloys. Surface microhardness added to the abrasive wear analysis showed the final wear resistance of the selected alloys. In addition, the shielding features against gamma and fast neutrons radiation were calculated. The superior characteristics of W-based alloys manufactured by powder technology make them suitable to be used in advanced nuclear power units.

A Novel Hydro-Thermal Synthesis of Nano-Structured Molybdenum-Iron Intermetallic Alloys at Relatively Low Temperatures.

Nano-structured Mo/Fe intermetallics were synthesized from precursors that contained 72/28% and 30/70% molar ratios of Mo/Fe, which were given as precursors A and B, respectively. These precursors were prepared from the co-precipitation of aqueous hot solutions of ammonium heptamolybdate tetrahydrate (AHM) and ferrous oxalate. The dry precipitates were thermally treated using TG-DSC to follow up their behavior during roasting, in an Ar atmosphere of up to 700 °C (10° K/min). The TG profile showed that 32.5% and 55.5% weight losses were measured from the thermal treatment of precursors A and B, respectively. The DSC heat flow profile showed the presence of endothermic peaks at 196.9 and 392.5-400 °C during the thermal decomposition of the AHM and ferrous oxalate, respectively. The exothermic peak that was detected at 427.5 °C was due to the production of nano-sized iron molybdate [Fe2(MoO4)3]. An XRD phase analysis indicated that iron molybdate was the only phase that was identified in precursor A, while iron molybdate and Fe2O3 were produced in precursor B. Compacts were made from the pressing of the nano-sized precursors, which were roasted at 500 °C for 3 h. The roasted compacts were isothermally reduced in H2 at 600-850 °C using microbalance, and the O2 weight loss that resulted from the reduction reactions was continuously recorded as a function of time. The influence of the reduction temperature and precursor composition on the reduction behavior of the precursors was studied and discussed. The partially and completely reduced compacts were examined with X-ray powder diffraction (XRD), a reflected light microscope (RLM), and a scanning electron microscope (SEM-EDS). Depending on the precursor composition, the reduction reactions of the [Fe2(MoO4)3] and Fe2O3 proceeded through the formation of intermediate lower oxides, prior to the production of the MO/Fe intermetallic alloys. Based on the intermediate phases that were identified and characterized at the early, intermediate, and final reduction degrees, chemical reaction equations were given to follow up the formation of the MoFe and MoFe3 intermetallic alloys. The mechanism of the reduction reactions was predicted from the apparent activation energy values (Ea) that were computed at the different reduction degrees. Moreover, mathematical formulations that were derived from the gas-solid reaction model were applied to confirm the reduction mechanisms, which were greatly dependent on the precursor composition and reduction temperature. However, it can be reported that nano-structured MoFe and MoFe3 intermetallic alloys can be successfully fabricated via a gas-solid reaction technique at lower temperatures.

Developing a Virtual Flowability Sensor for Monitoring a Pharmaceutical Dry Granulation Line.

Current technologies to measure granule flowability involve at-line methods that can take hours to perform. This is problematic for a continuous dry granulation tableting line, where the quality assurance and control of the final tablet products depend on real-time monitoring and control of powder flowability. Hence, a real-time alternative is needed for measuring the flowability of the granular products coming out of the roller compactor, which is the unit operation immediately preceding the tablet press. Since particle analyzers have the potential to take inline measurements of the size and shape of granules, they can potentially serve as real-time flowability sensors, given that the size and shape measurements can be used to reliably predict flowability measurements. This paper reports on the use of Partial Least Squares (PLS) regression to utilize distributions of size and shape measurements in predicting the output of three different types of flowability measurements: rotary drum flow, orifice flow, and tapped density analysis. The prediction performance of PLS had a coefficient of determination ranging from 0.80 to 0.97, which is the best reported performance in the literature. This is attributed to the ability of PLS to handle high collinearity in the datasets and the inclusion of multiple shape characteristics-eccentricity, form factor, and elliptical form factor-into the model. The latter calls for a change in industry perspective, which normally dismisses the importance of shape in favor of size; and the former suggests the use of PLS as a better way to reduce the dimensionality of distribution datasets, instead of the widely used practice of pre-selecting distribution percentiles.

Continuous Feeding and Blending Demonstration with Co-Processed Drug Substance.

Continuous direct compression (CDC) of solid oral dosage forms requires materials exhibiting acceptable flow and compression properties. The desired active pharmaceutical ingredient (API) powder properties can be difficult to achieve through conventional particle engineering approaches, such as particle size and habit modification during crystallization. Co-processing of API with excipients can significantly improve the powder properties to overcome these difficulties. In this manuscript, performance of a co-processed API was evaluated in a continuous feeding and blending process using GEA ConsiGma® Continuous Dosing and Blending Unit (CDB1). The co-processed theophylline was generated via a methodology in which polymer was precipitated and coated the crystalline theophylline particles resulting in nearly spherical agglomerates. A range of drug loads (1-25% w/w), flow rates (15-40 kg/h) and blender speeds (220-400 rpm) were studied. The results demonstrated that the co-processed API can be successfully fed through a loss-in-weight feeder and blended with other excipients in a high shear blender to generate tablets with acceptable content uniformity at 1-25% w/w drug loads. This study supports that using co-processed API with enhanced powder properties is a promising approach to enable continuous manufacturing for APIs with challenging properties.

Coating of Primary Powder Particles Improves the Quality of Binder Jetting 3D Printed Oral Solid Products.

Binder jetting (BJ) 3D printing is especially suitable for the fabrication of an orodispersible solid dosage form, as it is an efficient way to avoid the use of mechanical forces typical for compaction-based processes. However, one of the existing challenges related to pharmaceutical applications of BJ is the relatively high amount of binder needed in the primary powder to ensure the sufficient mechanical strength of printed products. In this study, a strategy based on pre-processing with a thin layer coating was explored. With this strategy, the matrix particles (lactose monohydrate) of the primary powder for BJ 3D printing were coated with the binder (polyvinylpyrrolidone, PVP). The investigated compositions of the primary powder contained PVP at three levels, namely, 10 %, 15% and 20% (w/w). The primary powder compositions were prepared with or without the coated lactose powder, and they were subsequently 3D BJ printed into oral solid products with paracetamol as a model active drug substance. The presence of coated lactose in the primary powder increased the interparticulate interactions in the BJ 3D printed products. Especially for the composition with a relatively small amount of binder (i.e., 10% and 15% w/w PVP in the primary powder), the use of coated particles significantly improved the resistance to crushing and decreased the disintegration time of printed products. In conclusion, thin layer coating is an effective way to pre-process primary powder particles for BJ 3D printing of oral solid products.

Synthesizinge a novel Zr2Al-GNS MAX phase ceramic with superior electrical properties using pressureless sintering technique.

A unique Zr2Al-GNS MAX phase ceramic supported nanographene sheet was prepared using a cost-effective pressureless sintering technique under relatively low temperature. An experimental investigation was conducted to explore the lattice parameters using different temperatures, such as 1000, 1150, and 1300 °C. To characterize the crystal structure of the MAX phase ceramic, X-ray diffraction, field emission scanning electron microscopy imaging, energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM), and selected area diffraction (SAED) were utilized. The results revealed that the pressureless sintering technique was successfully utilized to synthesize the Zr2Al-GNS MAX phase ceramic under 1150 °C with a low impurity ratio of secondary phases such as Zr3AL2, Zr3AL5, and ZrC components. The high percentage of the Zr2Al-GNS MAX phase ceramic was obtained at 49.0% at 1150 °C compared with different temperatures. The BET surface area (SBET), pore volume, and pore size were also investigated. The SBET of the prepared Zr2Al-GNS MAX phase was increased to 30% using graphene nanosheet, while the porosity was highly decreased to 8% from its original value. The electrical properties were also studied in this research for potential applications, such as the absolute value of impedance (Z), absolute value of admittance (Y), induction (L), capacitance (C), resistance (R), conductance (G), susceptibility (B), and phase angle (Ï´). It was found that the capacitance and the phase angle were improved using the prepared Zr2Al-GNS MAX phase ceramic, depending on the frequencies. The results presented here may facilitate the improvements in the features of the MAX phase type of Zr2Al-GNS-enhanced one-layer nanographene sheet for electrical applications ceramic.

Solid-state properties of pink clay from Jequitinhonha Valley in Brazil for pre-formulation study

Abstract Clay minerals are still widely used in pharmaceutical products for human health and cosmetic purposes. Pre-formulation studies were conducted to identify solid-state properties of pink clay, a sample from Diamantina, Brazil. Among the solid properties to be analyzed, we have selected type identification, iron phases, crystallinity, powder flow characteristics, thermal behavior, and non-isothermal phase transition kinetics. The pink clay is composed of (1:1) clay type and kaolinite as the main component. The Mössbauer spectrum of pink clay shows Fe3+(α-Fe2O3) Clay minerals are still widely used in pharmaceutical products for human health and cosmetic purposes. Pre-formulation studies were conducted to identify solid-state properties of pink clay, a sample from Diamantina, Brazil. Among the solid properties to be analyzed, we have selected type identification, iron phases, crystallinity, powder flow characteristics, thermal behavior, and non-isothermal phase transition kinetics. The pink clay is composed of (1:1) clay type and kaolinite as the main component. The Mössbauer spectrum of pink clay shows Fe3+(α-Fe2O3) hematite, Fe2+, and Fe3+ with large Δ/2ξq of about 2.80 and 2.69 mm.s-1 respectively, related to iron silicates, most likely pyroxene, and a superparamagnetic Fe3+. Pink clay exhibits poor flow properties. The thermal behavior indicates a phase-transition between 400 - 600 ºC associated with the dehydroxylation of the pink clay system requiring ~300 kJ mol-1, being constant until the process reaches a conversion of ~50% when the energy is enhanced to ~530 kJ mol-1, concluding the whole dehydroxylation process (α=80%). Solid-state properties and characteristics found for the pink clay must be considered for the proper design of formulations. This type of clay shows unique pharmaceutical properties that can be favorably exploited by the cosmetic industry

Dry Powder Inhalers for Proteins Using Cryo-Milled Electrospun Polyvinyl Alcohol Nanofiber Mats.

To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the preparation processes, may result in the degradation and denaturation of drugs such as those based on peptides and proteins. Here, we showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. The cryo-milled nanofiber mats were porous to fine particles, and the particle size and drug stability depended on the freezing and milling times. The median diameter of the milled fiber mats was 12.6 µm, whereas the mass median aerodynamic diameter was 5.9 µm. The milled nanofiber mats were successfully prepared, while retaining the enzymatic activity of α-chymotrypsin; furthermore, the activity of milled fiber mats that had been stored for 6 months was comparable to the activity of those that were freshly prepared. This novel method may be suitable for the DPI preparation of various drugs because it avoids the heating step during the DPI preparation process.

Structural and Optical Characterization of Mechanochemically Synthesized CuSbS2 Compounds.

One of the areas of research on materials for thin-film solar cells focuses on replacing In and Ga with more earth-abundant elements. In that respect, chalcostibite (CuSbS2) is being considered as a promising environmentally friendly and cost-effective photovoltaic absorber material. In the present work, single CuSbS2 phase was synthesized directly by a short-duration (2 h) mechanochemical-synthesis step starting from mixtures of elemental powders. X-ray diffraction analysis of the synthesized CuSbS2 powders revealed a good agreement with the orthorhombic chalcostibite phase, space group Pnma, and a crystallite size of 26 nm. Particle-size characterization revealed a multimodal distribution with a median diameter ranging from of 2.93 µm to 3.10 µm. The thermal stability of the synthesized CuSbS2 powders was evaluated by thermogravimetry and differential thermal analysis. No phase change was observed by heat-treating the mechanochemically synthesized powders at 350 °C for 24 h. By UV-VIS-NIR spectroscopy the optical band gap was determined to be 1.41 eV, suggesting that the mechanochemically synthesized CuSbS2 can be considered suitable to be used as absorber materials. Overall, the results show that the mechanochemical process is a viable route for the synthesis of materials for photovoltaic applications.

Effect on Microstructure and Mechanical Properties of Microwave-Assisted Sintered H13 Steel Powder with Different Vanadium Contents.

The present work demonstrated the first-ever preparation of block specimens by the microwave sintering of H13 alloy powder. Varying proportions of vanadium powder (1.5%, 2.5%, 3.5%, 4.5%, and 5.5% on a mass basis) were added to H13 mold steel and these mixtures were sintered using microwaves. X-ray fluorescence spectroscopy was employed to determine the compositions of the resulting specimens and vanadium percentages of 1.56%, 2.04%, 3.10%, 4.06%, and 4.20% were determined. These results demonstrate a clear trend, with significantly lower vanadium amounts than expected based on the nominal values at higher vanadium loadings. Different samples were also found to exhibit different degrees of ablation, and this effect was related to the presence of voids in the materials. The surface compositions of these specimens were examined by laser-induced breakdown spectroscopy and were found to be relatively uniform. The microstructures as well as the hardness properties of the materials were assessed. Microwave sintering of 100 g specimens at 1300 °C for 10-min generated samples with hardness values ranging from 205 HV (at the lowest vanadium content) to 175.2 HV (at the highest vanadium content). The wear behavior of samples prepared by microwave sintering H13 die steel with different vanadium contents at room temperature has been studied. The results showed that 1.5% vanadium content is the best mass ratio.

Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process.

While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the process is in a state of control, and as a controlled variable in process control system design. In current continuous tableting line operations, the pharmaceutical community relies on loss-in-weight feeders to monitor and understand upstream powder flow dynamics. However, due to the absence of established sensing technologies for measuring particulate flow rates, the downstream flow of the feeders is monitored and controlled using various indirect strategies. For example, the hopper level of the tablet press is maintained as a controlled process output by adjusting the turret speed of the tablet press, which indirectly controlling the flow rate. This gap in monitoring and control of the critical process flow motivates our investigation of a novel PAT tool, a capacitance-based sensor (ECVT), and its effective integration into the plant-wide control of a direct compaction process. First, the results of stand-alone experimental studies are reported, which confirm that the ECVT sensor can provide real-time measurements of mass flow rate with measurement error within -1.8 ~ 3.3% and with RMSE of 0.1 kg/h over the range of flow rates from 2 to 10 kg/h. The key caveat is that the powder flowability has to be good enough to avoid powder fouling on the transfer line walls. Next, simulation case studies are carried out using a dynamic flowsheet model of a continuous direct compression line implemented in Matlab/Simulink to demonstrate the potential structural and performance advantages in plant-wide process control enabled by mass flow sensing. Finally, experimental studies are performed on a direct compaction pilot plant in which the ECVT sensor is located at the exit of the blender, to confirm that the powder flow can be monitored instantaneously and controlled effectively at the specified setpoint within a plant-wide feedback controller system.

[Advances in Pharmaceutical Manufacturing Process Management -From Physical Pharmaceutics to Automatic Pharmaceutical Production].

Since entering graduate school 43 years ago, I have been studying physical pharmaceutics with a focus on the effects of environmental factors on pharmaceutical properties of solid oral dosage forms during the manufacturing process. I have reported on changes in the characteristics of pharmaceutical products during manufacturing processes, such as grinding, mixing, granulation, and tableting owing to complicated phenomena based on chemical reactions or the crystalline polymorphic transitions of bulk drugs and excipients. To develop modern pharmaceutical manufacturing processes based on process analysis technology (PAT) as a next generation good manufacturing practice, real-time monitoring was introduced in these processes using a non-destructive analytical method, such as the near-infrared spectroscopy combined with chemometrics. Many case studies related to the mixing, granulation, tableting, and coating processes involving PAT have been reported. In those studies, I focused on clarifying the physical and chemical mechanism through "design space" representation. Additionally, non-destructive analytical methods, including X-ray computed tomography, audible acoustic emission, Raman spectroscopy, terahertz spectroscopy, and infrared thermal imaging analysis were applied as novel candidate analytical methods to the pharmaceutical process to monitor critical quality attributes. To achieve this purpose in various pharmaceutical dosage forms, I have been attempting the assembly of a modern manufacturing process managed through a "design space" paradigm involving in-line monitoring using novel analytical methods, multivariate analyses, and feed-back systems.

Effect of Nanostructuring on the Thermoelectric Properties of ß-FeSi2.

Nanostructured ß-FeSi2 and ß-Fe0.95Co0.05Si2 specimens with a relative density of up to 95% were synthesized by combining a top-down approach and spark plasma sintering. The thermoelectric properties of a 50 nm crystallite size ß-FeSi2 sample were compared to those of an annealed one, and for the former a strong decrease in lattice thermal conductivity and an upshift of the maximum Seebeck's coefficient were shown, resulting in an improvement of the figure of merit by a factor of 1.7 at 670 K. For ß-Fe0.95Co0.05Si2, one observes that the figure of merit is increased by a factor of 1.2 at 723 K between long time annealed and nanostructured samples mainly due to an increase in the phonon scattering and an increase in the point defects. This results in both a decrease in the thermal conductivity to 3.95 W/mK at 330 K and an increase in the power factor to 0.63 mW/mK2 at 723 K.

Mechanical Milling: A Superior Nanotechnological Tool for Fabrication of Nanocrystalline and Nanocomposite Materials.

Throughout human history, any society's capacity to fabricate and refine new materials to satisfy its demands has resulted in advances to its performance and worldwide standing. Life in the twenty-first century cannot be predicated on tiny groupings of materials; rather, it must be predicated on huge families of novel elements dubbed "advanced materials". While there are several approaches and strategies for fabricating advanced materials, mechanical milling (MM) and mechanochemistry have garnered much interest and consideration as novel ways for synthesizing a diverse range of new materials that cannot be synthesized by conventional means. Equilibrium, nonequilibrium, and nanocomposite materials can be easily obtained by MM. This review article has been addressed in part to present a brief history of ball milling's application in the manufacture of a diverse variety of complex and innovative materials during the last 50 years. Furthermore, the mechanism of the MM process will be discussed, as well as the factors affecting the milling process. Typical examples of some systems developed at the Nanotechnology and Applications Program of the Kuwait Institute for Scientific Research during the last five years will be presented in this articles. Nanodiamonds, nanocrystalline hard materials (e.g., WC), metal-matrix and ceramic matrix nanocomposites, and nanocrystalline titanium nitride will be presented and discussed. The authors hope that the article will benefit readers and act as a primer for engineers and researchers beginning on material production projects using mechanical milling.

Continuous mixing technology: Validation of a DEM model.

Continuous powder mixing is an important technology used in the development and manufacturing of solid oral dosage forms. Since critical quality attributes of the final product greatly depend on the performance of the mixing step, an analysis of such a process using the Discrete Element Method (DEM) is of crucial importance. On one hand, the number of expensive experimental runs can be reduced dramatically. On the other hand, numerical simulations can provide information that is very difficult to obtain experimentally. In order to apply such a simulation technology in product development and to replace experimental runs, an intensive model validation step is required. This paper presents a DEM model of the vertical continuous mixing device termed CMT (continuous mixing technology) and an extensive validation workflow. First, a cohesive contact model was calibrated in two small-scale characterization experiments: a compression test with spring-back and a shear cell test. An improved, quicker calibration procedure utilizing the previously calibrated contact models is presented. The calibration procedure is able to differentiate between the blend properties caused by different API particle sizes in the same formulation. Second, DEM simulations of the CMT were carried out to determine the residence time distribution (RTD) of the material inside the mixer. After that, the predicted RTDs were compared with the results of tracer spike experiments conducted with two blend material properties at two mass throughputs of 15 kg/h and 30 kg/h. Additionally, three hold-up masses (500, 730 and 850 g) and three impeller speeds (400, 440 and 650 rpms) were considered. Finally, both RTD datasets from DEM and tracer experiments were used to predict the damping behavior of incoming feeder fluctuations and the funnel of maximum duration and magnitude of incoming deviations that do not require a control action. The results for both tools in terms of enabling a control strategy (the fluctuation damping and the funnel plot) are in excellent agreement, indicating that DEM simulations are well suited to replace process-scale tracer spike experiments to determine the RTD.

A Pathway From Porous Particle Technology Toward Tailoring Aerogels for Pulmonary Drug Administration.

Pulmonary drug delivery has recognized benefits for both local and systemic treatments. Dry powder inhalers (DPIs) are convenient, portable and environmentally friendly devices, becoming an optimal choice for patients. The tailoring of novel formulations for DPIs, namely in the form of porous particles, is stimulating in the pharmaceutical research area to improve delivery efficiency. Suitable powder technological approaches are being sought to design such formulations. Namely, aerogel powders are nanostructured porous particles with particularly attractive properties (large surface area, excellent aerodynamic properties and high fluid uptake capacity) for these purposes. In this review, the most recent development on powder technologies used for the processing of particulate porous carriers are described via updated examples and critically discussed. A special focus will be devoted to the most recent advances and uses of aerogel technology to obtain porous particles with advanced performance in pulmonary delivery.

Understanding Deformation Behavior and Compression Speed Effect in Gabapentin Compacts.

Deformation mechanism and strain rate sensitivity of gabapentin powder was investigated in this work. Heckel analysis, specific surface area and indentation hardness measurements revealed an intermediate yield pressure and brittle fracture as the dominant type of deformation mechanism during consolidation. Strain rate sensitivity of gabapentin was studied by compressing it at 1 mm/min and 500 mm/min compression speeds. Gabapentin demonstrated an atypical strain rate sensitivity in compactibility profile (tensile strength vs. solid fraction). Compacts of gabapentin compressed at fast speed showed an increase in tensile strength when compared with those compressed at slow speed. To understand the effect of compression speed on gabapentin's compactibility, PXRD analysis, surface area analysis, indentation hardness measurements, and consolidation modeling were performed. PXRD analysis carried out on compacts revealed no effect of speed on the physical solid-state stability of gabapentin. Specific surface area of compacts made at fast speed was higher than that of compacts made at slow speed. Indentation measurements performed on gabapentin compacts showed higher values of hardness in the case compacts made at fast speed. It was identified that at the fast compression speed, gabapentin shows greater particle fragmentation and form compacts with smaller pores.