Milling Of Ribbons Research Articles

The influence of milling of ribbons on selected granule quality attributes and carvedilol release from roller-compacted hypromellose-based matrix tablets

Roller compaction is gaining importance in the pharmaceutical industry. This study evaluates the impact of ribbon milling conditions on properties of granules and compression mixtures and on drug release from hypromellose-based matrix tablets prepared with two different fillers. In the first part of the study, design of experiments (DoE) was utilized to investigate the effect of filler type (lactose and microcrystalline cellulose (MCC)), mill type (oscillating, conical and hammer mill), milling speed and the size of screen apertures on selected attributes (granule particle size distribution (PSD), porosity and shape), and on the compressibility and compactibility of compression mixtures. The effect of DoE factors and selected attributes on the release of carvedilol at different timepoints of the release profile (t = 1–7 h) was further assessed. The study showed that drug release was affected by filler type, mill type, and various attributes; however, their effect proved to be complex and strongly related to granule PSD. Therefore, this effect was minimized in the second part of the study, in which tablets containing the same amount of different particle size fractions of granules were prepared with different mills and fillers. The drug release profiles confirmed that drug release is mainly related to differences in filler type and granule PSD. However, they indicate that with lactose mill type also affected drug release, possibly due to differences identified in particle shape.

Implementation of spatial filtering technique in monitoring roller compaction process

This study investigates the use of the spatial filtering technique (SFT11spatial filtering technique) to monitor the particle size distribution (PSD22particle size distribution) of granules obtained by roller compaction. In the first part of the study, the influence of the selected process and formulation parameters on the PSD2 of granules is monitored at-line using SFT1. The correlation between the PSD2 obtained by SFT1, sieve analysis, laser diffraction, and dynamic image analysis was satisfactory. The same trend was observed with all methods; however, SFT1 proved to be especially advantageous for monitoring the PSD2 of irregularly shaped granules obtained by roller compaction. Another aim of this study was to investigate the suitability of using the SFT1 method as a potential process analytical technology (PAT33process analytical technology) tool for monitoring and predicting the PSD2 of granules obtained by roller compaction. The SFT1 model for d10 was poor due to less precise detection of smaller particles by SFT; nevertheless, the models for d50 (R2 = 0.93) and d90 (R2 = 0.93) were very good. The at-line models were further tested in real time on samples collected during the milling of ribbons. The correlation between the predicted and achieved values was good; however, it was time and formulation dependent.

Magnetic and Thermal Studies of Iron-Based Amorphous Alloys Produced by a Combination of Melt-Spinning and Ball Milling

In this study, we demonstrate the synthesis of an Fe78Si9B10P3 amorphous alloy by three pathways: mechanical alloying, melt-spinning and a combination of melt-spinning and ball milling. Microstructure, thermal stability and soft magnetic properties of the melt-spun and mechanically alloyed powders are comparatively studied. Ball milling of previously melt-spun samples led to an amorphous powder with an average particle size of ~2.4 μm after 20 hrs of milling. Mechanical alloying of elemental Fe-Si-B-P powders in a planetary ball mill for up to 100 hrs led only to a partial amorphisation of powder with a median particle size of ~1.3 μm. Differential thermal analysis of the amorphous ribbon revealed that the amorphous phase was stable up to ~520 °C, at which the crystallization process occurred. The melt spun ribbons exhibited excellent soft ferromagnetic behavior, including high saturation magnetization (Ms) of ~171 emu/g and a low coercivity (Hc) of ~2.8 Oe. In the 20 hrs milled ribbons, due to a probable partial anisotropy which induced by ball milling stress, the Ms value decreased slightly to ~161 emu/g but the Hc increased to ~38 Oe. The mechanically alloyed samples present a relatively lower Ms of ~154 emu/g and higher Hc of ~43 Oe. It is to be noted that the milling of ribbons is usually inevitable due to their technological restrictions in use.

Impact of feed material properties on the milling of pharmaceutical ribbons: A PBM analysis.

Dry granulation is commonly used in the pharmaceutical industry for compressing heat and moisture sensitive feed materials into compacts, subsequently followed by milling. Population balance models (PBMs) are often used to explore the effects of milling conditions on the granule size distribution (GSD) but limited studies have investigated the effects of the feed material and ribbon properties on the resulting GSD. In this work, a variety of feed materials and ribbons with different mechanical properties were used to validate a mass-based bi-modal breakage function developed in a previous study (Olaleye et al., 2019). Ribbon like tablets (referred to as ribblets) with a range of precisely controlled porosities were produced using an Instron machine and pharmaceutical excipients including the microcrystalline cellulose MCC 101, MCC DG and a DCPA/MCC mixture. Roll compacted ribbons were also produced using MCC 102 and MCC DG excipients. The ribblets and ribbons were milled in an impact-dominated cutting mill and PBM parameters were obtained from the ribblet milling data. Mechanistic models related to the feed ribbon property were then developed. It was found that the PBM with the mass-based bi-modal breakage function can accurately predict the GSDs of both the milled ribblets and roll compacted ribbons. The model developed was successfully linked to ribbon properties such as porosity for the first time and the model parameter a that reflects the fines mode in the bi-modal breakage function increased linearly with ribblet porosity. This work demonstrates the versatility of the developed PBM and provides a systematic approach for describing the ribbon milling process.

Population balance modelling of ribbon milling with a new mass-based breakage function.

Dry granulation through roll compaction followed by milling is a widely used pharmaceutical process. The material properties of powders and the roll compaction process conditions affect the strength of ribbons, and subsequently the granule size distribution (GSD). Accurate prediction of the granule size distribution from milling of ribbons with different properties is essential for ensuring tablet quality in the final compaction stage. In this study, MCC, PH-102 ribbons with precisely controlled porosities were produced and milled in a cutting mill and granule size distribution was analysed using QicPic. A population balance model with a new breakage function based on the Weibull function was developed to model the ribbon milling process. Eight model parameters were initially obtained for each ribbon porosity and very good agreement between the model and experimental results was obtained. Sensitivity analysis was then performed and thus reduced the number of model parameters that changed with ribbon porosity to two in the breakage function. The refined model was able to predict the granule size distribution both within and outside the experimental boundaries. It was shown that the model developed in this study has a great potential for predicting granule properties and therefore the optimisation of the dry granulation process.

A novel use of friability testing for characterising ribbon milling behaviour

Dry granulation using roll compaction (DGRC) has been increasingly adopted in the pharmaceutical industry due to its unique advantage of not requiring liquid binder and a subsequent drying process. However the DGRC process presents also some challenges, in particular, a high fine fraction generated during the milling stage significantly limits its application. Although the fines produced can be recycled in practice, it may lead to poor content uniformity of the final product. At present there is a lack of mechanistic understanding of milling of roll compacted ribbons. For instance, it is not clear how fines are generated, what are the dominant mechanisms and controlling attributes and whether any measurement technique can be used to characterise ribbon milling behaviour. Therefore, the aim of this paper was to assess whether ribbon milling behaviour can be assessed using some characterisation methods. For this purpose, friability was evaluated for ribbons made of microcrystalline cellulose (MCC) powders using a friability tester that was originally developed for characterising the tendency of pharmaceutical tablets to generate small pieces while being abraded. Granules were also produced by milling of the ribbons and their size distributions were measured. The correlation between the fine fraction of the granules with ribbon friability was then explored. It was found that there was a strong correlation between ribbon friability and the fine fraction of granules generated during milling. This implies that friability tests can be performed to characterise ribbon milling behaviour, and ribbon friability provides a good indication of the fraction of fines generated during ribbon milling.

Magneto-structural transformations in Ni50Mn37.5Sn12.5−xInx Heusler powders

The effect of ball milling and subsequently annealing of melt spun ribbons on magneto-structural transformations in Ni50Mn37.5Sn12.5−xInx (x=0, 2, 4, 6) ribbons is presented. Short time vibration milling allows to obtain chemically homogenous powders of angular particle shapes and size within 10–50μm. Milling does not change the characteristic temperatures of martensitic transformation in comparison to the melt spun ribbons. The effect of In substitution for Sn on martensitic transformation has a complex mechanism, associated with electron density change. Substitution of Sn by In in both milled and annealed powders leads to decrease of Curie temperature of austenite and increase of martensitic transformation temperature, stabilizing martensitic phase. The coexistence of magnetic transformation of austenite and martensitic transformation at low magnetic field was observed. The intermartensitic transformation of 4O martensite to L10 martensite was observed during cooling at low magnetic field and this was confirmed by TEM microstructure observations. The annealing process of as-milled powders leads to the change of their martensitic structure due to relaxation of internal stresses associated with anisotropic columnar grain microstructure formed during melt spinning process. The level of stresses introduced during milling of ribbons has no significant influence on martensitic transformation. The annealing process of as milled powders leads to enhancement of their magnetic properties, decrease of Curie temperature of austenite, and marginal change of temperature of martenisitic transformation.

The use of positron emission particle tracking (PEPT) to study milling of roll-compacted microcystalline cellulose ribbons

Milling is a critical process for controlling the properties of the granules produced by roll compaction. In the current study, the positron emission particle tracking (PEPT) technique was used to examine the milling kinematics of roll-compacted ribbons at various milling speeds. Microcrystalline cellulose (MCC, Avicel PH-102) was used as the model feed material and a radioactive particle (tracer) was mixed with the MCC powder and roll-compacted to form sample ribbons. They were then milled using an oscillating mill at various speeds and the kinematics of the ribbons (trajectory, velocity, and occupancy) were quantitatively determined using PEPT. A close examination of the PEPT data reveals that, for milling MCC PH-102 ribbons using the oscillating mill considered in this study, the milling speed plays an important role: at low values, the milling process is dominated by cooperative motion of the ribbons with the blade (i.e. the speeds of the ribbons and the blade are similar, and the ribbons move along with the blade) and the ribbons are milled primarily by abrasion; as the speed increases the ribbons undergo more random motion involving collisions that results in an increase in ribbon breakage and hence an increase in the milling efficiency. It is shown that the PEPT technique is a useful technique for examining milling kinematics of roll-compacted ribbons.

Effects of sintering temperature on microstructure and property evolution of Fe81Cu2Nb3Si14 soft magnetic materials fabricated from amorphous melt-spun ribbons by spark plasma sintering technique

Bulk Fe81Cu2Nb3Si14 soft magnetic materials were fabricated by spark plasma sintering (SPS) of amorphous powder, which was prepared by ball milling of melt-spun ribbons. Effects of sintering temperature on the evolution of microstructure and related properties were systematically investigated. Results show that the as-milled powders exhibit similar microstructure and thermal property in comparison with the original melt-spun ribbons. With an increase in the sintering temperature, the relative density, microhardness and saturation magnetization of the sintered samples improved obviously, but the coercive force decreased at the beginning and then increased with the increase of sintering temperature. The sintered samples exhibit typical soft magnetic characteristic. The desirable soft magnetic property of the sintered samples was achieved by SPS at 630°C. Meanwhile, microstructure and densification behaviors of the sintered samples were also investigated.

Structure and soft magnetic properties of the bulk samples prepared by compaction of the mixtures of Co-based and Fe-based powders

Ball milling of CoFeZrB ribbons and subsequent compaction of the resulting powders were used to prepare bulk amorphous samples. Further, two sets of powder samples were prepared by cryomilling of FeCuNbMoSiB alloy in amorphous and nanocrystalline state. Amorphous and nanocrystalline FeCuNbMoSiB powders were blended with CoFeZrB powder at different concentrations. Such powder mixtures were consolidated and several bulk nanocomposites have been synthesized. An addition of nanocrystalline or amorphous FeCuNbMoSiB powder to amorphous CoFeZrB powder caused a decrease of the magnetostriction of the resultant bulk samples, while the coercivity shows an opposite behavior. Our results show that the powder consolidation by hot pressing is an alternative method for the preparation of bulk metallic glasses, which are difficult to prepare by casting methods.

Preparation and soft magnetic properties of bulk amorphous Co-rich alloys

Ferromagnetic bulk compacts were synthesized by compaction of either milled or cryomilled Co 70.3Fe 4.7B 25 alloy. Short milling of as-quenched ribbons caused its crystallization whereas cryomilling suppreses it. Optimized milling and compaction parameters allowed obtaining bulk samples without significant degree of crystallinity. Achieved values of coercivity of the bulk samples reflect the strong dependence on the microstructure.

Fabrication and structure of bulk nanocrystalline Al–Si–Ni–mishmetal alloys

Al-based alloys of structure consisting of nanosized Al crystals, embedded in an amorphous matrix, are interesting for their excellent mechanical properties, exceeding those of the commercial crystalline Al-based alloys. Recently discovered nanocrystalline Al alloys containing silicon (Si), rare earth metal (RE) and late transition metal (Ni), combine high tensile strength and good wear resistance. The aim of this work was to manufacture bulk nanocrystalline alloys from Al–Si–Ni–mishmetal (Mm) system. Bulk nanostructured Al 91− x Si x Ni 7Mm 2 ( x = 10, 11.6, 13 at.%) alloys were produced by ball milling of nanocrystalline ribbons followed by high pressure hot isostating compaction.

Hydrogen storage in Mg–Ni–Fe compounds prepared by melt spinning and ball milling

Magnesium-rich Mg–Ni–Fe intermetallic compounds have been prepared by two different routes: (a) short time ball milling of ribbons obtained by melt spinning; (b) long time ball milling of a mixture of MgH 2, Ni and Fe powders. The first type of samples displays an hydrogen desorption kinetics better than the second one. Pressure composition isotherm measurements exhibit for both type of samples two plateaux, the lower and wider corresponding to the MgH 2 phase and the upper and shorter corresponding to the Mg 2NiH 4 phase. The presence of the two types of hydrides is confirmed by X-ray diffraction analysis. Mössbauer spectroscopy shows that in melt spun and subsequently milled samples iron is mainly in a disordered structure and segregates after hydrogenation, while in directly milled powders remains mainly unalloyed. After multiple hydrogen absorption/desorption cycles the main part of iron is in metallic state in samples of both types, those of first type preserving better hydrogen desorption kinetics.

Synthesis, Structure and Properties of Iron-Based Bulk Glass-Forming Metallic Alloys Prepared by Different Processing

This article deals with the materials science and engineering of glass-forming alloys in Fe-(Nb)-(Al, Ga)-(P, C, B, Si), Fe-(Cr, Mo, Ga)-(P, C, B) and Fe-(Co, Ni)-(Cu)-(Zr, Nb)-B bulk metallic glasses (BMG) systems with high thermal stability of the undercooled melt against crystallization. Different liquid quenching techniques (melt-spinning or copper-mold casting) as well as hot pressing of the powder obtained by milling of the melt-spun ribbons were used to prepare samples in various shapes. Synthesis of the investigated BMG alloys is discussed according to Inoue’s empirical components rules for the achievement of the large glass forming ability (GFA). Thermal and microstructure characterization (performed by DSC, TMA, XRD and Mössbauer spectroscopy) was used to correlate GFA, microstructure and thermo/thermo-magnetic treatments with optimum soft magnetic properties.

Nanocrystallization during nanoindentation of a bulk amorphous metal alloy at room temperature.

It is known that nanocrystallites can form in shear bands produced during severe bending or high-energy ball milling of thin ribbons of a metallic glass. We present direct experimental evidence that highly confined and controlled local contact at the ultrafine scale in the form of quasi-static nanoindentation of a bulk glassy metal alloy at room temperature can also cause nanocrystallization. Atomic force microscopy and transmission electron microscopy show that nanocrystallites nucleate in and around shear bands produced near indents and that they are the same as crystallites formed during annealing without deformation at 783 kelvin. Analogous to results from recent experiments with glassy polymers, our results are reasoned to be a consequence of flow dilatation inside the bands and of the attendant, radically enhanced, atomic diffusional mobility inside actively deforming shear bands.