Enhanced Flow Properties Research Articles

Enhancing Flow Properties and Preventing Sticking and Picking in Tablet Formulations: Exploring the Efficacy of StarTab® as a Multifunctional Additive

This study investigates the flow and compression behaviour of four excipients (StarTab®, MCC, Mannitol, Lactose) when combined with caffeine as a model drug for direct compression. Notably, pure caffeine particles demonstrate high adhesion to punch and die walls. However, the incorporation of StarTab®led to improved flow of the pre-blend, along with reductions in detachment stress (DS) and ejection stress (ES) during tabletting. Contrarily, blending caffeine with MCC, Mannitol, and Lactose did not result in considerable improvements in flow properties and also did not address sticking and picking issues. The potential of StarTab® in enhancing flow properties and addressing sticking issues in pharmaceutical applications is highlighted. These findings contribute to optimizing formulations for efficient tablet production.

Preparation and characterisation of biocomposites containing thermomechanical pulp fibres, poly(lactic acid) and poly(butylene-adipate-terephthalate) or poly(hydroxyalkanoates) for 3D and 4D printing

Wood fibres are hygroscopic and swell when immersed in water. This effect can be used to create shape-changing structures in 3D printing. Hence, wood fibre reinforced filaments have the potential to be used in four-dimensional (4D) printing. In this work, biocomposites based on granulated or milled thermomechanical pulp (TMP) fibres and poly(lactic acid) (PLA) were prepared and evaluated based on their tensile properties. Poly(hydroxyalkanoates) (PHA) or poly(butylene-adipate-terephthalate) (PBAT) were included in the biocomposite recipes to assess their effect on the melt flow index (MFI) and tensile properties. Clear effects of the TMP fibre morphology on MFI were quantified. Biocomposites containing 20 wt% PBAT turned out to be stronger and tougher than the ones containing PHA. Based on that, filaments for 3D and 4D printing were manufactured. Interestingly, the tensile strength of 3D printed specimens containing milled TMP (TMPm) fibres was about 33% higher compared to those containing TMP fibre granulate (TMPg). Using hot water as the stimulus, the 3D printed specimens containing TMPg showed a greater reactivity and shape change compared to TMPm specimens. • Differences in TMP fibre morphology affect the melt-flow-index of biocomposites. • PBAT elastomer ensures the manufacturing of strong and tough biocomposites with enhanced flow properties for 3D printing. • 3D printed parts with shorter TMP fibre fragments showed greater tensile strength and were less brittle. • Mono- and bi-material 3D printed biocomposite causes shape morphing properties, using water as an external stimulus.

Applications of Helical Versus Straight Hollow Fiber Membranes: A Review

The production of straight and helical hollow fibers plays an important role in developing hollow fiber membrane technology that encompasses a broad range of designs. During the last two decades, scientific studies devoted to straight hollow fibers were more abundant than those focused on helical fibers. Several major applications considering side-by-side testing of these two geometries are discussed in this review. For membrane extraction, desalination, and membrane contactor processes, it is observed that permeability rates are 10%-400 % higher for helical fibers compared to straight fibers. This outcome is justified by the presence of Dean-vortices-induced flow turbulences inherent to the geometry of helical membranes. These conditions give rise to an uptake of mass and heat transfer coefficients and a reduction of temperature and concentration polarization phenomena. Aside from enhanced flow properties, helical hollow fiber bundles tend to be more robust by design, thus exhibiting better resiliency over long service operations than straight bundles. One persistent shortcoming of the helical fibers seems to be an increase in pressure drop. However, this does not always translate into a higher energy consumption – i.e., versus straight bundles. Given the performance advantage, product robustness, and adaptiveness to a broad range of applications, the adoption of helical hollow fiber technology deserves growing support from the membrane community in academic and industrial settings.

Determination of limiting factors in a novel superconcentration-granulation based dairy powder manufacturing process

An innovative approach based on superconcentration and granulation was investigated to manufacture dairy ingredients at lab-scale. A wet mass characterization technique, which measured agitator current consumption, was developed to study cohesiveness of super-concentrated products at various dry matter (DM) contents. For all ingredients, a composition-dependent cohesive phase was observed as DM increased, which was typified by a sharp rise and subsequent fall in power consumption. The effect of powder back-mixing on granulation was studied using three superconcentrate:powder (w/w) ratios (1:0.8, 1:1 and 1:1.2, respectively). Minimum powder addition rate for successful granulation was related to DM content at the end of the cohesive phase. Granulated powders had larger particle size, higher densities, lower porosities and enhanced flow properties compared to commercial spray-dried powders. The lab-scale model provided useful information on physical properties and limits during superconcentration and granulation, which increases the scientific knowledge relating to this novel powder production approach. Industrial relevanceSpray drying is the most widely utilized powder manufacturing technology in the dairy industry, especially for producing ingredients and nutritional products. It is, however, extremely energy intense and therefore spray drying of high-volume, low-value dairy streams such as permeate represents a poor use of resources for industry. An alternative spray dryer-free process has been developed for such streams, with significant savings. This process is based on superconcentration of streams to DM content in excess of what is typically seen in a spray-drying process (up to 80% w/w DM) followed by granulation achieved by back-mixing of finished product and, finally, drying of granules. However, little information is available on how various dairy ingredients behave in this system. Therefore, a novel lab-scale production model was produced to determine limits of superconcentration and granulation behavior of various ingredients. This work provides vital information and represents the first step in a larger program which will culminate in demonstration of the industrial applicability of the new approach for drying of various dairy streams.

HOT MELT EXTRUSION IN ENGINEERING OF DRUG COCRYSTALS: A REVIEW

Crystal engineering technique has been widely explored in recent times to bring about changes in crystallinity which aids to achieve various goals such as solubility enhancement, stability and in vivo bioavailability without altering the chemical properties of the drug. Cocrystallisation is one of the crystal engineering approaches where the drug and an inert coformer are linked together by hydrogen bonding forming supramolecular homosynthon or heterosynthon using solvent-based or solvent-free techniques. Processing of active pharmaceutical ingredients with inert water-soluble coformers yields multicomponent crystalline cocrystals with high-performance characteristics and enhanced flow properties. Due to the emerging need of the industry for greener techniques, hot melt extrusion (HME), a continuous and solvent-free process is emerging as a field of interest in the mechanochemical synthesis of various pharmaceutical dosage forms such as solid dispersions, implants, ointments, and cocrystals. The current review emphasizes the role of HME as a cocrystallization technique for drugs to tailor-make their properties and ease of formulation. The distinct feature of HME is phase control during the process of cocrystallization. Furthermore, the selection of appropriate coformers with desirable water-solubility and stability features makes HME amenable to cocrystallization of versatile actives yielding suitable dosage forms. The application of process analytical technology further adds ease of monitoring during HME in cocrystallization approaches. Due to these salient features of HME, it can act as a prospective technique for cocrystallization of versatile drugs thus yielding dosage forms with desirable solubility and stability features.

Synergistic application of twin-screw granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties

This study demonstrated the first case of combining a novel continuous granulation technique with powder-bed fusion-based selective laser sintering (SLS) process to enhance the dissolution rate and physical properties of a poorly water-soluble drug. Selective laser sintering and binder jetting 3D printing processes have gained much attention in pharmaceutical dosage form manufacturing in recent times. These powder bed-based 3D printing platforms have been known to face printing and uniformity problems due to the inherent poor flow properties of the pharmaceutical physical mixtures. To address this issue a hot-melt extrusion-based versatile granulation process equipped with a process analytical technology (PAT) tool for the in-line monitoring of critical quality attributes (i.e., solid-state) of indomethacin was developed. The collected granules with enhanced flow properties were mixed with Kollidon® VA64 and a conductive excipient for efficient sintering. These mixtures were further characterized for their bulk properties observing an excellent flow and later subjected to an SLS-3D printing process. The physical mixtures, processed granules, and printed tablets were characterized using conventional as well as advanced solid-state characterizations. These characterizations revealed the amorphous nature of the drug in the processed granules and printed tablets. Further, the in vitro release testing of the tablets with produced granules as a reference standard depicted a notable dissolution advantage (100% drug released in 5 min at >pH 6.8) over the pure drug and the physical mixture. Our developed system known as DosePlus combines innovative continuous granulation and SLS-3D printing process which can potentially improve the physical properties of the bulk drug and formulations in comparison to when used in isolation. This process can further find application in continuous manufacturing of granules and additive manufacturing of pharmaceuticals to produce dosage forms with excellent uniformity and solubility advantage.

Investigating thermodynamic, acoustic and spectroscopic parameters of rutin trihydrate with cationic surfactant CTAB in hydro-ethanolic solvent systems

The research work represents thermodynamic, acoustic and spectroscopic analysis of a well known flavonoid; rutin trihydrate and cationic surfactant; cetyltrimethyl ammonium bromide (CTAB). The studies were conducted at five different temperatures (20 °C, 25 °C, 30 °C, 35 °C and 40 °C) and four different hydro-ethanolic concentrations (aqueous, 30% v/v, 70% v/v and absolute ethanol). The critical micelle concentration (CMC) values were obtained by studying the deviation in plots of specific conductivity (κ) with respect to change in CTAB concentration. These values were utilized to calculate various thermodynamic parameters viz. standard enthalpy change (ΔHom), standard entropy change (ΔSom) and standard Gibbs free energy change (ΔGom) of micellization. To further investigate the nature of interactions and flow properties; density (ρ), ultrasonic sound velocity (μ) and relative viscosity (ηr) of the system were measured. The obtained values were further used to calculate various acoustic parameters i.e. apparent molar volume (ϕv) and apparent molar compressibility (ϕk). Moreover, the FTIR and 1H NMR spectroscopic analysis was performed to confirm micelle formation and to determine the locus of flavonoid in micellar structure of surfactant. From the overall studies; electrostatic and hydrophobic interactions in the system were identified and enhanced flow properties were observed.

Synthesis of Vixotrigine, a Voltage- and Use-Dependent Sodium Channel Blocker. Part 2: Development of a Late-Stage Process

As vixotrigine (1) entered a later clinical phase for trigeminal neuralgia (Zakrzewska, J. M.; et al. Lancet Neurol. 2017, 16, 291−300), the development of a sustainable late-stage process was required to meet the supply needs for formulation optimization, phase 3 clinical trials, and registration stability batches (this is the expected commercial formulation). In this article, we describe how the process was streamlined from the early supply route (Giblin, G.; et al. Org. Process Res. Dev. 2020, DOI: 10.1021/acs.oprd.0c00382) and a comprehensive control strategy was established. Process improvements included improving safety and scalability for a temperature-sensitive Grignard reaction, simplifying unit operations, removal of heterogenous conditions, and route redesign to afford a high yielding, one-pot sequential alkylation and amidation. Improvement in the salt formation step, combined with wet milling, resulted in improved particle properties with enhanced flow properties of the final active pharmaceutical ingredient. The process mass intensity was improved 65% while maintaining drug substance purity at more than 99.8%. This new process has been scaled up to generate metric ton quantities of drug substance.

Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis

Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL.

Studies on Naturally Extracted Surfactant to Enhance Flow Properties of Crude Oil

Indian heavy crude oil sample from Gujarat was studied for improvement of properties such as pour point, wax crystal structure, particle size analysis and viscosity by addition of a novel surfactant extracted from a tropical Indian plant Sapindus mukorossi. Characterization was done to find the effect of surfactant addition on individual components of the crude oil such as saturates, asphaltenes, resins and aromatics. The objective was to increase the flowability of the oil and determine which components of the surfactant interact with the crude oil to improve its flow behavior. Heavy crude oil sample was mixed with 4% w/w of Sapindus followed by stirring the samples for one hour and proceeding for tests. The results showed that pour point decreased by a significant amount after adding Sapindus to it and that decrease in pour point was due to reduction in the amount of saturates, aromatics, resins and asphaltenes present in the crude oil. There was a profound reduction in size of wax crystals when investigated under microscopic and particle size analysis. Surfactant addition had a tremendous effect on viscosity. The viscosity of crude oil at 30°C after addition of surfactant, was even less than that of heavy crude without surfactant at 50°C.

Highly permeable twinned alumina nanoparticles for the precoat filtration of fine colloids

Abstract Pretreatment is key to the success of any fine filtration process. Precoat filtration is a common method to reduce fine particulate matter in feed streams. In this study, precoat filters were formed by the deposition of the diatomaceous earth (DE) or twinned alumina nanosheets (TAN) particles on a substrate. The TAN particles were produced via metal salt hydrolysis. The performance of the precoat filters was investigated during the constant-pressure filtration of a bentonite solution. The results showed that the TAN precoat exhibited enhanced flow properties and reduced the turbidity of the filtrate more rapidly than either of the DE precoats. The TAN precoat reached the required turbidity level of ≤0.10 NTU at a flux that was up to 28 times higher than the fluxes obtained by the DE precoats. The superior performance of the TAN precoat was explained by (1) the ability of the TAN precoat to resist compaction during filtration due to the unique twinning of the alumina nanosheets forming the TAN particles, (2) the strong attractive forces between the bentonite and TAN particles based on their opposite surface charges, and (3) the isotropic permeability of the TAN aggregates.

Self nanoemulsifying granules (SNEGs) of meloxicam: preparation, characterization, molecular modeling and evaluation of in vivo anti-inflammatory activity

Meloxicam, a BCS class II drug belonging to the class of NSAIDs is indicated in conditions of rheumatoid arthritis, ankylosing spondylitis and osteoarthritis in which rapid onset of drug action is desired to reduce inflammation and pain. The objective of the study was to thus develop Self Nanoemulsifying Granules (SNEGs) of Meloxicam (MLX) for enhancement of solubility; and subsequently dissolution rate, thus aiming for a faster onset of action. Preliminary studies along with molecular modeling studies were carried out for selection of appropriate lipids, surfactants and cosurfactants for the development of MLX-loaded Self Nanoemulsifying preconcentrate (SNEP). A charge inducer was incorporated into the formulation so as to increase the solubility of MLX in lipids and hence, drug loading. A three-factor D-optimal mixture design was used for optimization of MLX loaded SNEP. The role of charge inducer in increasing the drug loading of MLX in SNEDDS was studied by molecular dynamics simulation using Desmond. Optimized SNEP was adsorbed onto solid carriers to form SNEGs for improved stability and enhanced flow properties. Physical characterization studies of SNEGs, in vitro release studies, and in vivo evaluation of anti-inflammatory activity of the optimized formulation were performed. All the results indicated that MLX SNEGs can be a promising alternative to conventional oral NSAIDs therapy because of enhanced dissolution characteristics and subsequent rapid onset of action.

Investigation of novel extracted surfactant on rheological properties of heavy crude oil

Naturally extracted surfactant from tropical Indian plant Madhuca longifolia was used to enhance flow properties of heavy crude oil through pipelines. Experimental measurements include viscosity, yield stress, viscoelastic properties, pour point, SARA analysis, microscopic studies and FTIR studies. Experimental verification of Power Law model was justified. Crude oil surfactant mixtures tend to behave like Newtonian fluid as surfactant concentration was increased from 500 to 2,000 ppm. Viscosity of crude with 2,000 ppm surfactant at 30°C was almost same as that of pure crude at 50°C. Presence of surfactant significantly reduced elastic and complex moduli of heavy crude oil at 30°C. Yield stress of crude oil reduced from 0.9 to 0.017 Pa with surfactant addition at 30°C. Microscopic studies showed surfactant addition reduced size of wax crystals appreciably. FTIR studies implied that aldehydic and amine groups are responsible for high viscosity and their concentration reduced after addition of surfactant Madhuca longifolia. [Received: August 4, 2015; Accepted: November 28, 2015]

Modern evaluation of liquisolid systems with varying amounts of liquid phase prepared using two different methods.

Liquisolid systems are an innovative dosage form used for enhancing dissolution rate and improving in vivo bioavailability of poorly soluble drugs. These formulations require specific evaluation methods for their quality assurance (e.g., evaluation of angle of slide, contact angle, or water absorption ratio). The presented study is focused on the preparation, modern in vitro testing, and evaluation of differences of liquisolid systems containing varying amounts of a drug in liquid state (polyethylene glycol 400 solution of rosuvastatin) in relation to an aluminometasilicate carrier (Neusilin US2). Liquisolid powders used for the formulation of final tablets were prepared using two different methods: simple blending and spraying of drug solution onto a carrier in fluid bed equipment. The obtained results imply that the amount of liquid phase in relation to carrier material had an effect on the hardness, friability, and disintegration of tablets, as well as their height. The use of spraying technique enhanced flow properties of the prepared mixtures, increased hardness values, decreased friability, and improved homogeneity of the final dosage form.

Enhanced Flow in Small-World Networks

The proper addition of shortcuts to a regular substrate can lead to the formation of a complex network with a highly efficient structure for navigation [J. M. Kleinberg, Nature 406, 845 (2000)]. Here we show that enhanced flow properties can also be observed in these small-world topologies. Precisely, our model is a network built from an underlying regular lattice over which long-range connections are randomly added according to the probability, Pij ∼ r−α ij , where rij is the Manhattan distance between nodes i and j, and the exponent α is a controlling parameter. The mean two-point global conductance of the system is computed by considering that each link has a local conductance given by gij ∝ r−C ij , where C determines the extent of the geographical limitations (costs) on the long-range connections. Our results show that the best flow conditions are obtained for C = 0 with α = 0, while for C ≫ 1 the overall conductance always increases with α. For C ≈ 1, α = d becomes the optimal exponent, where d is the topological dimension of the substrate. Interestingly, this exponent is identical to the one obtained for optimal navigation in small-world networks using decentralized algorithms.

Out-of-autoclave cure cycle study of a resin film infusion process using in situ process monitoring

Liquid resin infusion (LRI) of textile tailored reinforcements (TRs) is increasingly applied in new processing technologies for manufacturing carbon fibre composites. This work presents a cure cycle study of an out-of-autoclave toughened resin film infusion (RFI) process as part of the examination of an alternative manufacturing process for composites. To successfully produce laminates using resin film infusion in combination with a fast-curing process, the flow behaviour of the selected resin material under changed processing conditions was investigated. The effect of processing parameters, specifically heating rates and dwell times, on resin viscosity and laminate infiltration was evaluated through experimental work and supported by in situ process monitoring. A DC-resistance sensor system was applied to track the change in resin viscosity during cure. Results showed that cure cycles with a relatively short dwell time and higher heating rate compared to an autoclave cure led to enhanced flow properties of the toughened resin system. High quality laminates, comparable to autoclave panels, were manufactured with vacuum pressure only by modifying the original vacuum bagging arrangement.

Evaluation of the Release Profiles of Ibuprofen Formulated from Carnuba Wax and Homolipid Capra hircus

Purpose: To investigate the sustained release characteristics of ibuprofen lipospheres made from Capra hircus (GF) and carnauba wax (CW) in comparison with conventional granules as standard. Methods: Ibuprofen (90 g) and the lipid (30 g) were prepared by melt dispersion technique. Conventional granules of ibuprofen were prepared with starch mucilage, 20% w/v. Resulting lipospheres were characterized with respect to sizes, flow property, bulk and tap densities, encapsulated in hard gelatin capsules and evaluated for drug release profiles. Results: Dissolution profile for lipospheres were a maximum drug release of 97% in 1 hr (conventional granules), 23% in 4 hr (GF), 60% in 2 hr (CW) and 40% in admixtures of fats (GC). Admixing the fats enhanced flow properties of the lipospheres. Inclusion of a surfactant enhanced the release profiles from the lipospheres. Conclusion: Formulation of ibuprofen into lipospheres modified the release profile, which has implications in the formulation of sustained release multiunit dosage forms. Keywords: Carnuba wax, Capra hircus , Ibuprofen lipospheres, Dissolution profiles.

Near-Infrared Spectroscopy for the In-Line Characterization of Powder Voiding Part II: Quantification of Enhanced Flow Properties of Surface Modified Active Pharmaceutical Ingredients

In this work, dry-particle coating was used to modify the surface properties of active pharmaceutical ingredients (APIs) having extremely poor flow properties. Near-infrared (NIR) spectroscopy was utilized as a novel approach to characterize the improved flow behavior of APIs and their blends. Acetaminophen and ibuprofen were coated with nano-sized silica at two different coating levels (0.5% and 1% w/w of the API) in dry-particle coating devices viz. magnetically assisted impaction coater (MAIC) and Hybridizer. Surface modified (dry coated) APIs were then blended with excipient (spray dried lactose monohydrate) in a V-blender. As a baseline comparison to dry coating, the silica addition was also accomplished by two commonly used industry methods, i.e., passing a portion of API with silica through a sieve (sieve blending method) or blending a portion of API powder with silica in a V-blender (preblending method). Flow results showed that dry particle coated acetaminophen as well as ibuprofen blends performed significantly better than uncoated API blends at higher API concentrations. In addition, examination of the flow intensity from NIR spectra (inverse signal to noise ratio of spectra) and its standard deviation revealed that dry particle coated blends showed better uniformity of flow as compared to the other methods. Angle of repose measurements corroborated these results, showing that the majority of the blends prepared from coated APIs stayed in either passable or fair category.

Practical methods for improving flow properties of active pharmaceutical ingredients

Objective: The essential aim of this article is to develop effective methods for improving the flow properties of active pharmaceutical ingredients (APIs) without requiring particle size or shape modification. Methods: The ‘formulation’ approach used here focuses on enhancing flow properties of three chemically different drug powders (micronized acetaminophen, levalbuterol tartrate, and didesmethylsibutramine tartrate) by using small amounts of lubricants, glidants, and other additives, both individually and in combination. Additives are intimately mixed using a laboratory-scale V-blender with an intensifier bar. Flow index, dilation, and electrical impedance were measured for a total of 24 blends. Results: The flow behavior of all three APIs improved with the addition of these additives. Relative effectiveness of different additive combinations displayed remarkable consistency for all three APIs. Simultaneous presence of SiO2, MgSt, and talc led to substantial decreases in cohesiveness, causing major improvements in flowability of powder. All three properties showed a very tight correlation. Conclusions: Drug powders with improved flow were found to exhibit low dilation and low impedance values. A common linear correlation between flow index and impedance and also between dilation and impedance was observed for all three APIs, indicating that electric properties play a substantial role in the cohesivity of all three APIs, and suggesting the presence of a common mechanism for the emergence (and mitigation) of cohesive phenomena.

NICROBRAZ 152

Abstract Nicrobraz 152 is a high-chromium, oxidation-resistant nickel brazing filler metal with enhanced flow properties. This datasheet provides information on composition, physical properties, and tensile properties. It also includes information on corrosion resistance as well as forming, joining, and powder metal forms. Filing Code: Ni-674. Producer or source: Wall Colmonoy Corporation.