Bulk Properties Of Powders Research Articles

Process-Induced Crystal Surface Anisotropy and the Impact on the Powder Properties of Odanacatib.

Crystalline active pharmaceutical ingredients with comparable size and surface area can demonstrate surface anisotropy induced during crystallization or downstream unit operations such as milling. To the extent that varying surface properties impacts bulk powder properties, the final drug product performance such as stability, dissolution rates, flowability, and dispersibility can be predicted by understanding surface properties such as surface chemistry, energetics, and wettability. Here, we investigate the surface properties of different batches of Odanacatib prepared through either jet milling or fast precipitation from various solvent systems, all of which meet the particle size specification established to ensure equivalent biopharmaceutical performance. This work highlights the use of orthogonal surface techniques such as Inverse Gas Chromatography (IGC), Brunauer-Emmett-Teller (BET) surface area, contact angle, and X-ray Photoelectron Spectroscopy (XPS) to demonstrate the effect of processing history on particle surface properties to explain differences in bulk powder properties.

The Processing Space of the Spray-Dried Mannitol-Leucine System for Pulmonary Drug Delivery.

Designing spray-dried particles for inhalation aims at specific physicochemical properties including a respirable aerodynamic diameter and adequate powder dispersibility. Leucine, an amphiphilic amino acid, has been shown to aid in optimizing bulk powder properties. Mannitol, a model crystalline active and common bulking agent, was co-sprayed with leucine at several excipient ratios, ethanol/water ratios, and spray dryer outlet temperatures in order to experimentally probe the underlying particle formation mechanisms in this binary crystalline system. During the droplet drying of two crystallizing components, the material that nucleates first will preferentially enrich the surface. It is desired to have a completely crystalline leucine shell to improve powder properties, however, mannitol competes with leucine for the surface depending on excipient concentration and manufacturing parameters. The resulting particles were studied initially and at a two-month timepoint via solid state characterization, visual analysis, and particle size analysis in order to detect changes in bulk powder properties. It was determined that, similar to systems where only leucine can crystallize, initial leucine saturation in the formulation dictates powder characteristics.

Precise particle size control during spherical agglomeration of benzoic acid by modification of the bridging liquid phase using TWEEN 20

The interest in spherical agglomeration processes in the pharmaceutical industry is rising due to the possibility of direct tableting of Active Pharmaceutical Ingredients and enhancements in bulk powder properties translating into improved powder processability. While agglomerating needle-shaped particles into spheres offers numerous advantages, such as improved flowability, filterability, and particle density, achieving precise control over the particle size and shape of the agglomerates remains a significant challenge. More specifically, the obtained agglomerate size rarely reaches values below 500 μm, which is the desired size range for pharmaceutical applications. To address this challenge, the current research investigates the effectiveness of incorporating surfactants at varying concentrations as a means to control the particle size and shape of the resulting agglomerates. Reversed addition antisolvent crystallization experiments were performed in ethanol/water using benzoic acid as a model compound, followed by the addition of a bridging liquid (toluene), which wets and bridges the single crystals into agglomerates. To modify the interfacial tension between the two immiscible liquid phases, different concentrations of the tween 20 surfactant were used, leading to a range of interfacial tensions spanning from 0.50 to 16.38 × 10−3 N/m. Both crystallization and agglomeration processes were monitored in situ using in-process microscopy tools. The experimental results demonstrated that by adjusting the surfactant concentration and thus the corresponding interfacial tension of the bridging liquid, highly tunable agglomerate sizes were achieved, ranging from 160 μm to 4412 μm. A higher surfactant concentration is correlated with smaller agglomerates and is key to control the final agglomerate size. However, it should be noted that the introduction of surfactants in the spherical agglomeration process negatively impacted the agglomerate's strength. Nonetheless, this method remains a promising and innovative technique for controlling the final particle size during spherical agglomeration.

Flowability of plant based food powders: Almond, chestnut, chickpea, coconut, hazelnut and rice

This study presents bulk material characterization, especially powder flowability, of eight food powders from six different plants (almond, chestnut, chickpea, coconut, hazelnut and rice). The characterization of the bulk powders includes the particle size distributions, true densities, bulk and tapped densities, as well as the powder porosity and moisture content. The flowability is determined by means of Hausner ratio, Carr's index, flow function by an annular shear cell and dynamic angle of repose. The flowability characteristics are discussed in regard to the bulk powder properties and evaluated for their applicability as some methods could give misleading results for the flowability.

Characterization of Avocado (Persea americana) Seed Starch - Physicochemical and Powder Properties

Introduction: Starch is a biopolymer commonly used as an excipient in pharmaceutical formulations due to its biocompatibility, inertness, biodegradability, availability and affordability. Purpose: The study aimed to extract and characterize the starch isolated from avocado (Persea americana) seeds and investigate its disintegrant and binder properties in paracetamol tablet formulations. Methods: Starch was extracted from avocado seed using standard methods and then subjected to some phytochemical, physicochemical and bulk powder properties analyses. High-resolution analyses using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and x-ray diffractometry (XRD) were also carried out on the extracted starch powder. Results: Starch extraction yield was 19.61% and the starch was light-brown in colour, odourless, tasteless and smooth in texture. The starch showed a melting point range of 102-114°C and moisture content of 22.7%. It also exhibited a hydration capacity of 2.76 g/g and swelling and moisture sorption capacities of 46.43 and 115.34%, respectively. The starch powder was cohesive with poor flow properties but the DSC, FTIR, SEM and XRD results showed a semi-crystalline powder composed of fluffy discrete particles. Conclusion: The starch isolated from P. americana seeds exhibited good swelling, hydration and moisture sorption capacities, making it a good candidate as a tablet disintegrant. Keywords: Avocado, starch, physicochemical, high-resolution, analyses

Densifying Co-Precipitated Amorphous Dispersions to Achieve Improved Bulk Powder Properties.

Precipitation of amorphous solid dispersions has gained traction in the pharmaceutical industry given its application to pharmaceuticals with varying physicochemical properties. Although preparing co-precipitated amorphous dispersions (cPAD) in high-shear rotor-stator devices allows for controlled shear conditions during precipitation, such aggressive mixing environments can result in materials with low bulk density and poor flowability. This work investigated annealing cPAD after precipitation by washing with heated anti-solvent to improve bulk powder properties required for downstream drug product processing. Co-precipitation dispersions were prepared by precipitation into pH-modified aqueous anti-solvent. Amorphous dispersions were washed with heated anti-solvent and assessed for bulk density, flowability, and dissolution behavior relative to both cPAD produced without a heated wash and spray dried intermediate. Washing cPAD with a heated anti-solvent resulted in an improvement in flowability and increased bulk density. The mechanism of densification was ascribed to annealing over the wetted Tg of the material, which lead to collapse of the porous co-precipitate structure into densified granules without causing crystallization. In contrast, an alternative approach to increase bulk density by precipitating the ASD using low shear conditions showed evidence of crystallinity. The dissolution rate of the densified cPAD granules was lower than that of the low-bulk density dispersions, although both samples reached concentrations equivalent to that of the spray dried intermediate after 90min dissolution. Hot wash densification was a tenable route to produce co-precipitated amorphous dispersions with improved properties for downstream processing compared to non-densified powders.

Effect of Hydrophobic Powders on the Tensile Strength of the Tablet

Zoe Chu1,2, Christopher Windows-Yule¹, Ian Gabbott², Gavin Reynolds², Rachael Shinebaum² and Andy Ingram¹1. School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT2. Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield, UKEmail: zhc906@student.bham.ac.ukIntroductionA tablet consists of the active pharmaceutical ingredients (API), and the other components, excipients. A tablet needs to withstand coating, packing and shipping stresses whilst maintaining the dissolution time; therefore, the tensile strength is of great importance. Currently, there is a lack of understanding on why excipients improve the bulk powder properties and the bonding mechanisms of the powder during compression. This makes tablet formulation development an inefficient trial-and-error process that is required for every new API (1). Literature has shown that the surface energy of the powders contributes a significant amount towards the tablet tensile strength. Hydrophobic powders have a lower surface energy (2) and are seen to disrupt this tablet strength (3,4).Experimental Aim and MethodThe aim was to investigate the impact of the hydrophobicity of excipient powders on tabletability of microcrystalline cellulose. This was done by mixing powders of varying hydrophobicity with MCC at varying mass fractions. There was focus on a lower mass fraction (0.02-0.1 m/m) with increasing increments of 0.02 m/m of added additive as well as gaining a global picture (0.2-1 m/m) with increments of 0.2 m/m.ResultsIt was found that at low mass fractions (0.02-0.4 m/m) of additive added the hydrophobic powders disrupted the tablet strength more compared to hydrophilic powders which could be attributed to the levels of surface energy of the additive. In contrast, at higher mass fractions (0.6-0.8 m/m), the surface energy is not as important and it is hypothesised that the deformation mechanisms of the additives governs the tablet strength.1. Reynolds GK, Campbell JI, Roberts RJ. A compressibility based model for predicting the tensile strength of directly compressed pharmaceutical powder mixtures. Int J Pharm [Internet]. 2017;531(1):215–24. Available from: http://dx.doi.org/10.1016/j.ijpharm.2017.08.0752. Sunkara D, Capece M. Influence of Material Properties on the Effectiveness of Glidants Used to Improve the Flowability of Cohesive Pharmaceutical Powders. AAPS PharmSciTech. 2018;19(4):1920–30. 3. Zuurman K, Maarschalk KVDV, Bolhuis GK. Effect of magnesium stearate on bonding and porosity expansion of tablets produced from materials with different consolidation properties. 1999;179:107–15. 4. Mishra SM, Rohera BD. Mechanics of tablet formation: a comparative evaluation of percolation theory with classical concepts. Pharm Dev Technol [Internet]. 2019;24(8):954–66. Available from: https://doi.org/10.1080/10837450.2019.1599913

Varied Bulk Powder Properties of Micro-Sized API within Size Specifications as a Result of Particle Engineering Methods.

Micronized particles are commonly used to improve the content uniformity (CU), dissolution performance, and bioavailability of active pharmaceutical ingredients (API). Different particle engineering routes have been developed to prepare micron-sized API in a specific size range to deliver desirable biopharmaceutical performance. However, such API particles still risk varying bulk powder properties critical to successful manufacturing of quality drug products due to different particle shapes, size distribution, and surface energetics, arising from the anisotropy of API crystals. In this work, we systematically investigated key bulk properties of 10 different batches of Odanacatib prepared through either jet milling or fast precipitation, all of which meet the particle size specification established to ensure equivalent biopharmaceutical performance. However, they exhibited significantly different powder properties, solid-state properties, dissolution, and tablet CU. Among the 10 batches, a directly precipitated sample exhibited overall best performance, considering tabletability, dissolution, and CU. This work highlights the measurable impact of processing route on API properties and the importance of selecting a suitable processing route for preparing fine particles with optimal properties and performance.

Influence of micro- and nano-bubble treatment on morphological characteristics and flow properties of spray-dried milk protein concentrate powders

This study investigated the morphological and bulk handling properties of milk protein concentrate (MPC) powders manufactured from incorporating micro- and nano-bubbles (MNB) before spray drying. Control MPC powders (C-MPC; no MNB treatment) and MNB-treated MPC powders (MNB-MPC; MPC dispersions passed through the MNB system and subsequently spray dried) were characterized in terms of particle size, shape factors, stability, variable flow rate, shear cell tests, compressibility, and wall friction. The MPC powders produced after the MNB injection process had better flowability and lower basic flow energy. Shear tests showed that C-MPC powders were more cohesive than MNB-MPC powders. The MNB-MPC powders had lower flow rate index values, lower wall friction angles, more rounded shape, and significant differences in powder compressibility compared with C-MPC powders. Overall, the results demonstrated that MNB incorporation during spray drying can produce ingredients with comparable morphological characteristics while improving the bulk powder properties.

A Directly Compressible Pregelatinised Sago Starch: A New Excipient in the Pharmaceutical Tablet Formulations.

An excipient intended for direct compression in pharmaceutical tableting must show important features of flowability and compactibility. This study investigated pregelatinised sago starch as an excipient for direct compression tablets. Pregelatinised sago starch was prepared and characterised. Its powder bulk properties and performance in the tablet formulations with paracetamol as a model drug were compared against two commercial, directly compressible excipients, namely Avicel® PH 101 and Spress® B820. The results showed that pregelatinisation did not affect the chemical structure of sago starch, but its degree of crystallinity reduced, and X-ray diffraction pattern changed from C-type to A-type. Powder bulk properties of pregelatinised sago starch and Spress® B820 were comparable, exhibiting better flowability but lower compactibility than Avicel® PH 101. In the formulation of paracetamol tablets, pregelatinised sago starch and Spress® B820 performed equally well, followed by Avicel® PH 101 as indicated in Formulations 3, 2 and 1, respectively.

Additive Manufacturing of Solid Products for Oral Drug Delivery Using Binder Jetting Three-Dimensional Printing

Binder jetting (BJ) three-dimensional (3D) printing is becoming an established additive manufacturing technology for manufacturing of solid products for oral drug delivery. Similar to traditional solutions based on compaction of powder mixture, successful processing of BJ products requires control of bulk powder properties. In contrast to traditional compaction-based process, BJ 3D printing allows for flexible modifications on microstructure, material composition and dose in the printed pharmaceutical products. Currently, systematic strategies for selecting excipients and optimizing the printing process have not been fully established. To address this challenge, a summary of the published work and selected patent literature around BJ 3D printing to fabricate pharmaceutical solid products for oral administration purposes is presented. First, an overview of characteristics of printed products as a part of the product design and a description of the commonly used excipients and active pharmaceutical ingredients is given. The critical powder and ink properties, as well as physical geometries and inner structures of a final product, are discussed in term of the mechanisms that determine the formation of a printed solid product and finally the quality of this product. This review is also summarizing the technical features of printers, printheads, and the critical considerations for post-processing procedures. BJ 3D printing is one of the most promising additive manufacturing technologies for mass customization of pharmaceutical products.

Assessing the Interrelationship of Microstructure, Properties, Drug Release Performance, and Preparation Process for Amorphous Solid Dispersions Via Noninvasive Imaging Analytics and Material Characterization.

The purpose of this work is to evaluate the interrelationship of microstructure, properties, and dissolution performance for amorphous solid dispersions (ASDs) prepared using different methods. ASD of GDC-0810 (50% w/w) with HPMC-AS was prepared using methods of spray drying and co-precipitation via resonant acoustic mixing. Microstructure, particulate and bulk powder properties, and dissolution performance were characterized for GDC-0810 ASDs. In addition to application of typical physical characterization tools, we have applied X-Ray Microscopy (XRM) to assess the contribution of microstructure to the characteristics of ASDs and obtain additional quantification and understanding of the drug product intermediates and tablets. Both methods of spray drying and co-precipitation produced single-phase ASDs. Distinct differences in microstructure, particle size distribution, specific surface area, bulk and tapped density, were observed between GDC-0810 spray dried dispersion (SDD) and co-precipitated amorphous dispersion (cPAD) materials. The cPAD powders prepared by the resonant acoustic mixing process demonstrated superior compactibility compared to the SDD, while the compressibility of the ASDs were comparable. Both SDD powder and tablets showed higher in vitro dissolution than those of cPAD powders. XRM calculated total solid external surface area (SA) normalized by calculated total solid volume (SV) shows a strong correlation with micro dissolution data. Strong interrelationship of microstructure, physical properties, and dissolution performance was observed for GDC-0810 ASDs. XRM image-based analysis is a powerful tool to assess the contribution of microstructure to the characteristics of ASDs and provide mechanistic understanding of the interrelationship.

Developing a metal powder specification for laser metal deposition

Jamie Clayton, operations director, Freeman Technology describes what particle and bulk powder properties need to be measured in order to successfully differentiate alternative supplies for laser metal deposition.

Optimizing Solvent Selection and Processing Conditions to Generate High Bulk-Density, Co-Precipitated Amorphous Dispersions of Posaconazole.

Co-precipitation is an emerging method to generate amorphous solid dispersions (ASDs), notable for its ability to enable the production of ASDs containing pharmaceuticals with thermal instability and limited solubility. As is true for spray drying and other unit operations to generate amorphous materials, changes in processing conditions during co-precipitation, such as solvent selection, can have a significant impact on the molecular and bulk powder properties of co-precipitated amorphous dispersions (cPAD). Using posaconazole as a model API, this work investigates how solvent selection can be leveraged to mitigate crystallization and maximize bulk density for precipitated amorphous dispersions. A precipitation process is developed to generate high-bulk-density amorphous dispersions. Insights from this system provide a mechanistic rationale to control the solid-state and bulk powder properties of amorphous dispersions.

The effect of powder age in high speed sintering of poly(propylene)

PurposeThis study aims to demonstrate for the first time that the cheap, commodity polymer, poly(propylene), can be successfully processed using high speed sintering, and that it can be recycled several times through the process, with little to no detriment to either the polymer itself or the parts obtained. This is significant as a step towards the realisation of high speed sintering as a technology for high-volume manufacturing.Design/methodology/approachA poly(propylene) powder designed for laser sintering was used to build parts on a high speed sintering machine. The unsintered powder was then collected and reused. Repeating this process allowed creation of seven generations of aged powder. A variety of characterisation techniques were then used to measure polymer, powder and part properties for each generation to discern any effects arising from ageing in the machine.FindingsIt was found that poly(propylene) could be used successfully in high speed sintering, albeit with a low build success rate. Increased powder age was found to correlate to an increase in the build success rate, changes in microscopic and bulk powder properties and improvement to the dimensional accuracy of the parts obtained. By contrast, no discernible correlations were seen between powder age and polymer molecular weight, or between powder age and the tensile properties of parts.Originality/valueThis is the first report of the use of poly(propylene) in high speed sintering. It is also first study regarding powder recyclability in high speed sintering, both in general and using poly(propylene) specifically.

Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro-In Silico Approach.

The use of physiologically based pharmacokinetic (PBPK) models to support drug product development has become increasingly popular. The in vitro characterization of the materials of the formulation provides valuable descriptors for the in silico prediction of the drug’s pharmacokinetic profile. Thus, the application of an in vitro–in silico framework can be decisive towards the prediction of the in vivo performance of a new medicine. By applying such an approach, this work aimed to derive mechanistic based insights into the potential impact of carrier particles and powder bulk properties on the in vivo performance of a lactose-based dry powder inhaler (DPI). For this, a PBPK model was developed using salbutamol sulphate (SS) as a model drug and the in vitro performance of its low-dose blends (2% w/w) with different types of lactose particles was investigated using different DPI types (capsule versus reservoir) at distinct airflows. Likewise, the influence of various carrier’s particle and bulk properties, device type and airflow were investigated in silico. Results showed that for the capsule-based device, low-dose blends of SS had a better performance, when smaller carrier particles (Dv0.5 ≈ 50 μm) with about 10% of fines were used. This resulted in a better predicted bioavailability of the drug for all the tested airflows. For the reservoir type DPI, the mean particle size (Dv0.5) was identified as the critical parameter impacting performance. Shear cell and air permeability or compressibility measurements, particle size distribution by pressure titration and the tensile strength of the selected lactose carrier powders were found useful to generate descriptors that could anticipate the potential in vivo performance of the tested DPI blends.

Influence of nitrogen gas injection and agglomeration during spray drying on the physical and bulk handling properties of milk protein concentrate powders

Abstract This study investigated the influence of injecting nitrogen (N2) gas under high pressure into milk protein concentrate (80%, w/w, protein; MPC) prior to spray drying and examining the physical and bulk handling properties of regular (non-agglomerated) and agglomerated powders. MPC powders produced using the N2 injection (NI) process had significantly lower bulk density and flowability, higher wall friction angles and increased levels of interstitial and occluded air. Agglomerated MPC powders had higher flow index values, lower wall friction angles, but were more friable, compared to regular powders. Surface composition analysis of MPC powders showed that NI caused fat to preferentially migrate to the surface in comparison to powders spray dried without NI. The results obtained in this study demonstrate that the injection of N2 into liquid MPC directly prior to spray drying, as well as agglomeration by fines return, can produce ingredients with unique particle and bulk powder properties.

Thermal rounding of micron-sized polymer particles in a downer reactor: direct vs indirect heating

Purpose The purpose of this paper is to investigate the effect of different heating approaches during thermal rounding of polymer powders on powder bulk properties such as particle size, shape and flowability, as well as on the yield of process. Design/methodology/approach This study focuses on the rounding of commercial high-density polyethylene polymer particles in two different downer reactor designs using heated walls (indirect heating) and preheated carrier gas (direct heating). Powder bulk properties of the product obtained from both designs are characterized and compared. Findings Particle rounding with direct heating leads to a considerable increase in process yield and a reduction in powder agglomeration compared to the design with indirect heating. This subsequently leads to higher powder flowability. In terms of shape, indirect heating yields not only particles with higher sphericity but also entails substantial agglomeration of the rounded particles. Originality/value Shape modification via thermal rounding is the decisive step for the success of a top-down process chain for selective laser sintering powders with excellent flowability, starting with polymer particles from comminution. This report provides new information on the influence of the heating mode (direct/indirect) on the performance of the rounding process and particle properties.

Improving the coloring of polypropylene materials for powder bed fusion by plasma surface functionalization

Polypropylene (PP) powder is treated in a fluidized bed reactor with an atmospheric Ar/O2 plasma jet to investigate the influence of the plasma treatment on the coloring of the powders. The oxygen concentration in the plasma gas and duration of the treatment was varied. Contact angle and X-ray photoelectron spectroscopy measurements confirmed and quantified the formation of surface functionalities and their dependence on the process parameters. The plasma treatment contributes to a significant improvement of the dispersibility and coloring of PP. Powder bulk properties such as particle size distribution and flowability were not modified by the process. Effects of the plasma treatment on the material bulk properties are also negligible.

Preparation, Physicochemical Characterisation and DoE Optimisation of a Spray-Dried Dry Emulsion Platform for Delivery of a Poorly Soluble Drug, Simvastatin.

In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as a model drug and solubilising oils, respectively. A matrix of the dry emulsions was composed at a fixed ratio mixture of mannitol and HPMC. Tween 20 was used in low amounts as the primary emulsion stabiliser. To facilitate process optimisation, a DoE surface response design was used to study the influence of formulation and process parameters on the particle size distribution, powder bulk properties, emulsion reconstitution ability, drug stability and process yield of spray-dried products. Two-fluid nozzle geometry was identified, studied and confirmed to be important for most product critical quality attributes. Models obtained after the study showed acceptable coefficients of determination and provided good insight in the relationship governing the process and product characteristics. Five model optimised products showed adequate process yield, suitable particle size distribution, good reconstitution ability and improved dissolution profile, when compared to a non-lipid-based tablet and the pure drug. However, the obtained dry emulsion powders exhibited poor flow character according to the Carr index. The optimised product was further analysed with NMR during lipolysis to gain insight into the species formed during digestion and the kinetics of their formation.