Particle Technology Research Articles

Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation

It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-ɛ-caprolactone/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-µ, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer.Graphical abstract

Spray Drying and Particle Engineering in Dosage Form Design for Global Vaccines.

Vaccines are a very important tool in the effort to reduce the global burden of infectious diseases. Modern vaccines can be formulated in several ways to induce specific immunity, including through the use of live bacteria, subunit antigens, and even genetic material. However, vaccines typically need to be transported and stored under controlled refrigerated or frozen conditions to maintain potency. This strict temperature control is incompatible with the available infrastructure in many developing countries. One method of improving the thermostability of a vaccine is through drying of a liquid presentation into a dry dosage form. In addition to enhancing the capability for distribution in resource-poor settings, these dry vaccine forms are more suitable for long-term stockpiling. Spray drying is a drying method that has been successfully used to stabilize many experimental vaccines into a dry form for storage above refrigerated temperatures. Additionally, the use of spray drying allows for the production of engineered particles suitable for respiratory administration. These particles can be further designed for increased out-of-package robustness against high humidity. Furthermore, there are already commercial dry powder delivery devices available that can be used to safely deliver vaccines to the respiratory system. The research in this field demonstrates that the resources to develop highly stable vaccines in flexible dosage forms are available and that these presentations offer many advantages for global vaccination campaigns.

Understanding the formation of ultrafine maltodextrin particles under simultaneous convective drying and antisolvent vapour precipitation

Research on simultaneous antisolvent-vapour-induced precipitation and convective drying of a solute-containing droplet was extensively conducted since this technique was introduced. However, the internal droplet compositions, which were suggested to be related to the formation of particle morphologies, had not been explored. Herein, the ethanol-vapour-induced precipitation of multi-solvent droplets containing maltodextrin as the solute was used to analyse internal droplet compositions. The droplet mass and diameter profiles were obtained via an established single-droplet drying experiment, which mimicked the spray drying of droplets. Analysis revealed that the antisolvent concentration increased with time and was higher than solvent concentration towards the end of the process. It is interesting to find out that the final particle morphology was profoundly impacted by the ambient ethanol humidity and also how spontaneous the subsequent drying was during ethanol-vapour-induced precipitation of the solutes. The formation of the porous structure was favoured with the occurrence of spontaneous vaporization once the ethanol was present for precipitation. Therefore, low ethanol humidity (20% ERH in this study) was sufficient. In contrast, higher ethanol humidity (>70% ERH) was preferable to produce spherical particles. This study provides an insight into particle engineering to unveil the internal droplet conditions and physical phenomena during this unique process.

Control of Drug-Excipient Particle Attributes with Droplet Microfluidic-based Extractive Solidification Enables Improved Powder Rheology

Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients (APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the production of neat or composite microparticles with precise control over key attributes that affect powder flowability, such as particle size distribution, particle morphology, composition, and the API's polymorphic form. However, the powder properties of these microparticles have not been well-studied due to the limited mass throughputs of available platforms. In this work, we produce spherical API and API-composite microparticles at high mass throughputs, enabling characterization and comparison of the bulk powder flow properties of these materials and greater understanding of how particle-scale attributes correlate with powder rheology. A multi-channel emulsification device and an extractive droplet-based method are harnessed to synthesize spherical API and API-excipient particles of artemether. As-received API and API crystallized in the absence of droplet confinement are used as control cases. Particle attributes are characterized for each material and correlated with a comprehensive series of powder rheology tests. The droplet-based processed artemether particles are observed to be more flowable, less cohesive, and less compressible than conventionally synthesized artemether powder. Co-processing the API with polycaprolactone to produce composite microparticles reduces the friction of the powder on stainless steel, a common equipment material. Droplet-based extractive solidification is an attractive particle engineering technique for improving powder processing and may aid in the implementation of continuous solid dosage form manufacturing.

Particle Engineering of Innovative Nanoemulsion Designs to Modify the Accumulation in Female Sex Organs by Particle Size and Surface Charge.

Particle engineering of nanosized drug delivery systems (DDS) can be used as a strategic tool to influence their pharmacokinetics after intravenous (i.v.) application by the targeted adaptation of their particle properties according to the needs at their site of action. This study aimed to investigate particle properties depending on patterns in the biodistribution profile to modify the accumulation in the female sex organs using tailor-made nanoemulsion designs and thereby to either increase therapeutic efficiency for ovarian dysfunctions and diseases or to decrease the side effects caused by unintended accumulation. Through the incorporation of the anionic phospholipid phosphatidylglycerol (PG) into the stabilizing macrogol 15 hydroxystearate (MHS) layer of the nanoemulsions droplets, it was possible to produce tailor-made nanoparticles with tunable particle size between 25 to 150 nm in diameter as well as tunable surface charges between −2 to nearly −30 mV zeta potential using a phase inversion-based process. Three chosen negatively surface-charged nanoemulsions of 50, 100, and 150 nm in diameter showed very low cellular toxicities on 3T3 and NHDF fibroblasts and merely interacted with the blood cells, but instead stayed inert in the plasma. In vivo and ex vivo fluorescence imaging of adult female mice i.v. injected with the negatively surface-charged nanoemulsions revealed a high accumulation depending on their particle size in the reticuloendothelial system (RES), being found in the liver and spleen with a mean portion of the average radiant efficiency (PARE) between 42–52%, or 8–10%, respectively. With increasing particle size, an accumulation in the heart was detected with a mean PARE up to 8%. These three negatively surface-charged nanoemulsions overcame the particle size-dependent accumulation in the female sex organs and accumulated equally with a small mean PARE of 5%, suitable to reduce the side effects caused by unintended accumulation while maintaining different biodistribution profiles. In contrast, previously investigated neutral surface-charged nanoemulsions accumulated with a mean PARE up to 10%, strongly dependent on their particle sizes, which is useful to improve the therapeutic efficacy for ovarian dysfunctions and diseases.

Pharmacokinetic and Pharmacodynamic studies of Omeprazole Co-crystals dry suspension

A novel omeprazole co-crystals instant dry suspension dosage was formulated by applying co-crystallization which is a particle engineering technique to enhance the physicochemical properties. As omeprazole has major critical draw backs in their solubility and stability (acidic pH degradation, thermal sensitivity, photosensitivity and highly hygroscopic nature) bioavailability of omeprazole was drastically reduced and purpose of administration of drug was not fulfilled. There by this formulation was invented to check maid these problems. In this present study in-vivo evaluation were performed. Pharmacokinetic parameters and pharmacodynamic parameters were determined and statistically analysed. The prepared formulation of omeprazole produced reliable satisfaction in solving the drawback problems of pure omeprazole by enhancing bioavailability. Statistical analysis was done by one way ANOVA test with P value less than 0.0001, Dunnet multiple comparison test was performed between the groups with P value < 0.01 which was considered to be significant.

Ultrasonic Atomization: New Spray Characterization Approaches

In particle engineering, spray drying is an essential technique that depends on producing sprays, ideally made of equal-sized droplets. Ultrasonic sprays appear to be the best option to achieve it, and Faraday waves are the background mechanism of ultrasonic atomization. The characterization of sprays in this atomization strategy is commonly related to the relation between characteristic drop sizes and the capillary length produced by the forcing frequency of wavy patterns on thin liquid films. However, although this atomization approach is practical when the intended outcome is to produce sprays with droplets of the same size, drop sizes are diverse in real applications. Therefore, adequate characterization of drop size is paramount to establishing the relations between empirical approaches proposed in the literature and the outcome of ultrasonic atomization in actual operating conditions. In this sense, this work explores new approaches to spray characterization applied to ultrasonic sprays produced with different solvents. The first two introduced are the role of redundancy in drop size measurements to avoid resolution limitation in the measurement technique and compare using regular versus variable bin widths when building the histograms of drop size. Another spray characterization tool is the Drop Size Diversity to understand the limitations of characterizing ultrasonic sprays solely based on representative diameters or moments of drop size distributions. The results of ultrasonic spray characterization obtained emphasize: the lack of universality in the relation between a characteristic diameter and the capillary length associated with Faraday waves; the variability on drop size induced by both liquid properties and flow rate on the atomization outcome, namely, lower capillary lengths produce smaller droplets but less efficiently; the higher sensibility of the polydispersion and heterogeneity degrees in Drop Size Diversity when using variable bin widths to build the histograms of drop size; the higher drop size diversity for lower flow rates expressed by the presence of multiple clusters of droplets with similar characteristics leading to multimodal drop size distributions; and the gamma and log-normal mathematical probability functions are the ones that best describe the organization of drop size data in ultrasonic sprays.

Improving LiNiO2 cathode performance through particle design and optimization

LiNiO2 cathode performance is improved through particle engineering. The present study identifies reduced surface reconstruction and preferential LiF formation on the (104) surface as main contributors to the improvement.

Aircraft Engine Particulate Matter and Gaseous Emissions from Sustainable Aviation Fuels: Results from Ground-Based Measurements During the Nasa/Dlr Campaign Eclif2/Nd-Max

Aircraft Engine Particulate Matter and Gaseous Emissions from Sustainable Aviation Fuels: Results from Ground-Based Measurements During the Nasa/Dlr Campaign Eclif2/Nd-Max

Macromolecular Engineering of Thermoresponsive Metal-Phenolic Networks.

Dynamic nanostructured materials that can react to physical and chemical stimuli have attracted interest in the biomedical and materials science fields. Metal-phenolic networks (MPNs) represent a modular class of such materials: these networks form via coordination of phenolic molecules with metal ions and can be used for surface and particle engineering. To broaden the range of accessible MPN properties, we report the fabrication of thermoresponsive MPN capsules using FeIII ions and the thermoresponsive phenolic building block biscatechol-functionalized poly(N-isopropylacrylamide) (biscatechol-PNIPAM). The MPN capsules exhibited reversible changes in capsule size and shell thickness in response to temperature changes. The temperature-induced capsule size changes were influenced by the chain length of biscatechol-PNIPAM and catechol-to-FeIII ion molar ratio. The metal ion type also influenced the capsule size changes, allowing tuning of the MPN capsule mechanical properties. AlIII-based capsules, having a lower stiffness value (10.7 mN m-1), showed a larger temperature-induced size contraction (∼63%) than TbIII-based capsules, which exhibit a higher stiffness value (52.6 mN m-1) and minimal size reduction (<1%). The permeability of the MPN capsules was controlled by changing the temperature (25-50 °C)─a reduced permeability was obtained as the temperature was increased above the lower critical solution temperature of biscatechol-PNIPAM. This temperature-dependent permeability behavior was exploited to encapsulate and release model cargo (500 kDa fluorescein isothiocyanate-tagged dextran) from the capsules; approximately 70% was released over 90 min at 25 °C. This approach provides a synthetic strategy for developing dynamic and thermoresponsive-tunable MPN systems for potential applications in biological science and biotechnology.

Advanced Microparticulate/Nanoparticulate Respirable Dry Powders of a Selective RhoA/Rho Kinase (Rock) Inhibitor for Targeted Pulmonary Inhalation Aerosol Delivery.

Pulmonary hypertension (PH) is a progressive disease that eventually leads to heart failure and potentially death for some patients. There are many unique advantages to treating pulmonary diseases directly and non-invasively by inhalation aerosols and dry powder inhalers (DPIs) possess additional unique advantages. There continues to be significant unmet medical needs in the effective treatment of PH that target the underlying mechanisms. To date, there is no FDA-approved DPI indicated for the treatment of PH. Fasudil is a novel RhoA/Rho kinase (ROCK) inhibitor that has shown great potential in effectively treating pulmonary hypertension. This systematic study is the first to report on the design and development of DPI formulations comprised of respirable nanoparticles/microparticles using particle engineering design by advanced spray drying. In addition, comprehensive physicochemical characterization, in vitro aerosol aerosol dispersion performance with different types of human DPI devices, in vitro cell-drug dose response cell viability of different human respiratory cells from distinct lung regions, and in vitro transepithelial electrical resistance (TEER) as air-interface culture (AIC) demonstrated that these innovative DPI fasudil formulations are safe on human lung cells and have high aerosol dispersion performance properties.

Optimization of Amorphization Kinetics during Hot Melt Extrusion by Particle Engineering: An Experimental and Computational Study

Optimization of Amorphization Kinetics during Hot Melt Extrusion by Particle Engineering: An Experimental and Computational Study

Lateral Flow Glyco-Assays for the Rapid and Low-Cost Detection of Lectins-Polymeric Linkers and Particle Engineering Are Essential for Selectivity and Performance.

Lateral flow immuno-assays, such as the home pregnancy test, are rapid point-of-care diagnostics that use antibody-coated nanoparticles to bind antigens/analytes (e.g., viruses, toxins or hormones). Ease of use, no need for centralized infrastructure and low-cost, makes these devices appealing for rapid disease identification, especially in low-resource environments. Here glycosylated polymer-coated nanoparticles are demonstrated for the sensitive, label-free detection of lectins in lateral flow and flow-through. The systems introduced here use glycans, not antibodies, to provide recognition: a “lateral flow glyco-assay,” providing unique biosensing opportunities. Glycans are installed onto polymer termini and immobilized onto gold nanoparticles, providing colloidal stability but crucially also introducing assay tunability and selectivity. Using soybean agglutinin and Ricinus communis agglutinin I (RCA120) as model analytes, the impact of polymer chain length and nanoparticle core size are evaluated, with chain length found to have a significant effect on signal generation—highlighting the need to control the macromolecular architecture to tune response. With optimized systems, lectins are detectable at subnanomolar concentrations, comparable to antibody-based systems. Complete lateral flow devices are also assembled to show how these devices can be deployed in the “real world.” This work shows that glycan-binding can be a valuable tool in rapid diagnostics.

Thermo-Mechanical Dry Coating as Dry Coating Process is for Pharmaceuticals

The manuscript aims to provide glimpse on updated information relating thermo-mechanical dry coating processes (TMDCP) suiting in modifying surface attributes of fine and ultra-fine particle (FiUlFiP). FiUlFiPs are the integral component of pharmaceutical processes. They exhibit complex and queer properties, are conferred mostly from their surface attributes colligated with their higher surface area. Particle engineering technocrats extensively working for modifying surface &amp; surface attributes of FiUlFiPs. These efforts are to find their worthy applications &amp; new functionalities. Among available diverse particle engineering technologies/ process, TMDCP, a dry coating process (DCP), advocated being worthy and efficient. The TMDCP finds multidisciplinary applications, mostly in drug development &amp; drug delivery. Said DCP involves fixing and/or attaching coating material (CoM) as particles herein synonym guest particle (GP) onto core/substrate particle (CSP) herein synonym host particle (HP). Attaching/ fixing the GPs onto HPs, in TMDCP, involve their mechanical and/or thermal interactions. Scientific literatures are evidencing diverse techniques and/or process, basing on discussed interactions. Amongst them novel techniques/ processes are Hybridization, Magnetically assisted impaction coating process (MAICP), Mechanofusion, Theta-composer, and high shear compaction. In this area diverse devices/ equipments are prevailing in market. Important are Hybridizer, Magnetically assisted impaction coater (MAIC), Theta-composer, Mechanofusion, Quadro Comil®, Cyclomix®, and many others. Attempt of this article is to discuss and present their method of working, working principle, applicability, limitations, and benefits. Contained information might be beneficial for professionals of pharmaceutical and allied field.&#x0D; Keywords: dry coating, equipment, particles, processes, thermo-mechanical.

Nebulizer systems: a new frontier for therapeutics and targeted delivery.

Drug delivery via the pulmonary route is a cornerstone in the pharmaceutical sector as an alternative to oral and parenteral administration. Nebulizer inhalation treatment offers multiple drug administration, easily employed with tidal breathing, suitable for children and elderly, can be adapted for severe patients and visible spray ensures patient satisfaction. This review discusses the operational and mechanical characteristics of nebulizer delivery devices in terms of aerosol production processes, their usage, benefits and drawbacks that are currently shaping the contemporary landscape of inhaled drug delivery. With the advent of particle engineering, novel inhaled nanosystems can be successfully developed to increase lung deposition and decrease pulmonary clearance. The above-mentioned advances might pave the path for treating a life-threatening disorder like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is also discussed in the current state of the art.

Hyaluronic Acid Hydrogels for Controlled Pulmonary Drug Delivery-A Particle Engineering Approach.

Hydrogels warrant attention as a potential material for use in sustained pulmonary drug delivery due to their swelling and mucoadhesive features. Herein, hyaluronic acid (HA) is considered a promising material due to its therapeutic potential, the effect on lung inflammation, and possible utility as an excipient or drug carrier. In this study, the feasibility of using HA hydrogels (without a model drug) to engineer inhalation powders for controlled pulmonary drug delivery was assessed. A combination of chemical crosslinking and spray-drying was proposed as a novel methodology for the preparation of inhalation powders. Different crosslinkers (urea; UR and glutaraldehyde; GA) were exploited in the hydrogel formulation and the obtained powders were subjected to extensive characterization. Compositional analysis of the powders indicated a crosslinked structure of the hydrogels with sufficient thermal stability to withstand spray drying. The obtained microparticles presented a spherical shape with mean diameter particle sizes from 2.3 ± 1.1 to 3.2 ± 2.9 μm. Microparticles formed from HA crosslinked with GA exhibited a reasonable aerosolization performance (fine particle fraction estimated as 28 ± 2%), whereas lower values were obtained for the UR-based formulation. Likewise, swelling and stability in water were larger for GA than for UR, for which the results were very similar to those obtained for native (not crosslinked) HA. In conclusion, microparticles could successfully be produced from crosslinked HA, and the ones crosslinked by GA exhibited superior performance in terms of aerosolization and swelling.

Particle Engineering of Chitosan and Kaolin Composite as a Novel Tablet Excipient by Nanoparticles Formation and Co-Processing.

Chitosan is not a common excipient for direct compression due to poor flowability and inadequate compressibility. Co-processing of chitosan and kaolin is a challenging method to overcome the limitations of the individual excipients. The purpose of the present study was to develop co-processed chitosan–kaolin by the spray drying technique (rotary atomizer spray dryer) and to characterize the excipient properties. The formation of chitosan nanoparticles was the major factor for desirable tablet hardness. The ratio of chitosan/tripolyphosphate of 10:1 and 20:1 had a significant effect on hardness. The successful development of co-processed chitosan–kaolin as a novel tablet excipient was obtained from a feed formulation composed of chitosan and kaolin at a ratio of 55:45 and the optimum chitosan/tripolyphosphate ratio of 20:1. Co-processing altered the physical properties of co-processed chitosan–kaolin in such a way that it enhanced the flowability and tableting performance compared to the physical mixture.

A review of emerging technologies enabling improved solid oral dosage form manufacturing and processing.

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight about the advances in tablet excipients, manufacturing, analytical techniques and deployment of Quality by Design (QbD). Various excipients offering novel functionalities such as solubility enhancement, super-disintegration, taste masking and drug release modifications have been developed. Furthermore, co-processed multifunctional ready-to-use excipients, particularly for tablet dosage forms, have benefitted manufacturing with shorter processing times. Advances in granulation methods, including moist, thermal adhesion, steam, melt, freeze, foam, reverse wet and pneumatic dry granulation, have been proposed to improve product and process performance. Furthermore, methods for particle engineering including hot melt extrusion, extrusion-spheronization, injection molding, spray drying / congealing, co-precipitation and nanotechnology-based approaches have been employed to produce robust tablet formulations. A wide range of tableting technologies including rapidly disintegrating, matrix, tablet-in-tablet, tablet-in-capsule, multilayer tablets and multiparticulate systems have been developed to achieve customized formulation performance. In addition to conventional invasive characterization methods, novel techniques based on laser, tomography, fluorescence, spectroscopy and acoustic approaches have been developed to assess the physical-mechanical attributes of tablet formulations in a non- or minimally invasive manner. Conventional UV-Visible spectroscopy method has been improved (e.g. fiber-optic probes and UV imaging-based approaches) to efficiently record the dissolution profile of tablet formulations. Numerous modifications in tableting presses have also been made to aid machine product changeover, cleaning, and enhance efficiency and productivity. Various process analytical technologies have been employed to track the formulation properties and critical process parameters. These advances will contribute to a strategy for robust tablet dosage forms with excellent performance attributes.

Particle Engineering and Spray Drying Process designing for Solubility Enhancement of Lopinavir

To improve the solubility enhancement of solid dispersion of Lopinavir by spray-drying by adding the Soluplus as polymer that is compatible with Lopinavir, was evaluated and the process used for preparation of Spray dried solid dispersion was validated and the 1:3 ratio used for preparation of solid dispersion. Dissolution tests were carried out on several spray dried solid dispersion of Lopinavir and physical mixture. The solid dispersion characterized by DSC, XRD, % Entrapment Efficiency, solubility study, drug content determination, practical yield, dissolution studies. Keyword: Lopinavir, Soluplus, Spray Drying Technique, Dissolution studies

A concise review on design and control of structured natural rubber latex particles as engineering nanocomposites

In this article, we review the modification of natural rubber (NR) latex into the engineered particles for make use of them in functional nanocomposites. The review focuses on tuning nano-/microstructure and/or composition of NR latex particles by means of surface chemical functionalization, structural modification and incorporation of inorganic nanoparticles (NPs). Due to their polydispersity in size and non-spherical shape with complicated indigenous stabilizers, i.e., proteins and lipids, we first describe the fundamental and common methods for the modification of synthetic polymer latex which become a practical guideline for engineering of NR particles to a variety of designs. Subsequently, the examples of successfully modified NR latex and the involved parameters in the preparation are discussed. The different nature and properties of the modified NR latex compared to the synthetic latex are then depicted. Finally, specific examples of these systems used in a range of applications including nanofillers, controlled releasing materials, textiles, electronics and coatings are demonstrated. The research on modification of NR latex particles would be beneficial to the field of materials science and engineering for the valorization of naturally abundant colloidal polymer to the advanced functional materials in the broader utilization/commercialization in the future.