Regime Map of the Effective Medium Approximation Modelling of Micro-Rough Surfaces in Ellipsometry.

In this work, we discuss the precision of the effective medium approximation (EMA) model in the data analysis of spectroscopic ellipsometry (SE) for solid materials with micro-rough surfaces by drawing the regime map. The SE parameters ψ (amplitude ratio) and Δ (phase difference) of the EMA model were solved by rigorous coupled-wave analysis. The electromagnetic response of the actual surfaces with micro roughness was simulated by the finite-difference time-domain method, which was validated by the experimental results. The regime maps associated with the SE parameters and optical constants n (refractive index) and k (extinction coefficient) of the EMA model were drawn by a comparison of the actual values with the model values. We find that using EMA to model micro-rough surfaces with high absorption can result in a higher precision of the amplitude ratio and extinction coefficient. The precisions of ψ, Δ, n and k increase as the relative roughness σ/λ (σ: the root mean square roughness, λ: the incident wavelength) decreases. The precision of ψ has an influence on the precision of k and the precision of Δ affects the precision of n. Changing σ alone has little effect on the regime maps of the relative errors of SE parameters and optical constants. A superior advantage of drawing the regime map is that it enables the clear determination as to whether EMA is able to model the rough surfaces or not.

[Application of quality by design in granulation process for ginkgo leaf tablet (⠣)： influence and control of raw materials' quality variation].

Raw materials' quality variation could affect the quality consistency of product and the clinical efficacy. In this paper, the high shear wet granulation (HSWG) process of the ginkgo leaf tablet was taken as the research object. Ginkgo biloba extracts and excipients microcrystalline cellulose collected from various sources and batches were used to simulate raw materials' quality variation. Real-time torque was recorded to analyze the viscosity of the wetting mass, and then by combining with physical fingerprint, the impact of physical quality variation of powders on granule properties could be investigated. Based on regime map thesis, whether the granules' nucleation mode was in mechanical dispersion regime was determined by calculating dimensionless parameters, which would lead to the unstable output in considerations of granule yield ratio and particle size distribution (PSD) curve. The orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties and the mediangranule size (D50) of Ginkgo biloba granules and then the critical material attributes (CMAs) were screened by variable importance in the projection (VIP) indexes. The results demonstrated that the properties of powders including hygroscopicity, angle of repose, Hausner ratio, Carr index, D10 and loss on drying affected the granule size. Besides, Ginkgo biloba granules were compressed into tablets. In view of tensile strength analysis, the raw materials' quality variation did not result in decrease of tensile strength of the ginkgo leaf tablets. The design space of critical quality attributes (CQAs) and the process design space which could cope with raw materials' quality variation were proved to be robust..

A Review of Pressure Drop and Mixing Characteristics in Passive Mixers Involving Miscible Liquids.

The present review focuses on the recent studies carried out in passive micromixers for understanding the hydrodynamics and transport phenomena of miscible liquid-liquid (LL) systems in terms of pressure drop and mixing indices. First, the passive micromixers have been categorized based on the type of complexity in shape, size, and configuration. It is observed that the use of different aspect ratios of the microchannel width, presence of obstructions, flow and operating conditions, and fluid properties majorly affect the mixing characteristics and pressure drop in passive micromixers. A regime map for the micromixer selection based on optimization of mixing index (MI) and pressure drop has been identified based on the literature data for the Reynolds number (Re) range (1 ≤ Re ≤ 100). The map comprehensively summarizes the favorable, moderately favorable, or non-operable regimes of a micromixer. Further, regions for special applications of complex micromixer shapes and micromixers operating at low Re have been identified. Similarly, the operable limits for a micromixer based on pressure drop for Re range 0.1 < Re < 100,000 have been identified. A comparison of measured pressure drop with fundamentally derived analytical expressions show that Category 3 and 4 micromixers mostly have higher pressure drops, except for a few efficient ones. An MI regime map comprising diffusion, chaotic advection, and mixed advection-dominated zones has also been devised. An empirical correlation for pressure drop as a function of Reynolds number has been developed and a corresponding friction factor has been obtained. Predictions on heat and mass transfer based on analogies in micromixers have also been proposed.

Development of a Granule Growth Regime Map for Twin Screw Wet Granulation Process via Data Imputation Techniques.

Twin screw granulation (TSG) is a continuous wet granulation technique that is used widely across different solid manufacturing industries. The TSG has been recognized to have numerous advantages due to its modular design and continuous manufacturing capabilities, including processing a wide range of formulations. However, it is still not widely employed at the commercial scale because of the lack of holistic understanding of the process. This study addresses that problem via. the mechanistic development of a regime map that considers the complex interactions between process, material, and design parameters, which together affect the final granule quality. The advantage of this regime map is that it describes a more widely applicable quantitative technique that can predict the granule growth behavior in a TSG. To develop a robust regime map, a database of various input parameters along with the resultant final granule quality attributes was created using previously published literature experiments. Missing data for several quality attributes was imputed using various data completion techniques while maintaining physical significance. Mechanistically relevant non-dimensional X and Y axis that quantify the physical phenomena occurring during the granulation were developed to improve the applicability and predictability of the regime map. The developed regime map was studied based on process outcomes and granule quality attributes to identify and create regime boundaries for different granule growth regimes. In doing so breakage-dominant growth was incorporated into the regime map, which is very important for TSG. The developed regime map was able to accurately explain the granule growth regimes for more than 90% of the studied experimental points. These experimental were generated at vastly different material, design, and process parameters across various studies in the literature, this further increases the confidence in the developed regime map.

A scaled down method for identifying the optimum range of L/S ratio in twin screw wet granulation using a regime map approach.

Twin screw wet granulation (TSWG) has gained momentum in the pharmaceutical industry for effective continuous granulation of solid dosage products. Liquid-to-solid (L/S) ratio is a key process parameter affecting granule properties. Identifying an optimum range of L/S ratio while reducing the number of full scale experiments can minimize material requirements and streamline formulation and process development. In this work, microcrystalline cellulose-based (MCC) formulations of varying drug loads were granulated using a kneading element screw configuration at a wide range of L/S ratios until pasting was visually determined. Quantitative criteria based on process relevant granule size and mass % of fines were established to identify undesirable granulation conditions. Key mechanical properties of wet compacts measured using a small scale approach are discussed. The stress-strain behavior is used to predict pasting, and natural strain at peak yield stress and total work of deformation are used to identify undergranulation and overgranulation respectively. The small scale method is used to establish viable ranges of L/S ratios in advance of at-scale experiments. A quantitative predictive growth regime map is proposed based fully on small scale experiments and input process parameters. Strategies for establishing a generalized growth regime map for various systems of interest are discussed.

Binary mixture droplet wetting on micro-structure decorated surfaces.

Liquid surface tension as well as solid structure play a paramount role on the intimate wetting and non-wetting regimes and interactions between liquids droplets and solid substrates. We hypothesise that the coupling of these two variables, independently addressed in the past, eventually offer a wider range of understanding to the surface science and interfacial communities. In this work, intrinsically hydrophobic micro-pillared surfaces varying in the spacing between structures, and pure ethanol, pure water and their binary mixtures (as well as acetone-water and ethylene glycol-water mixtures) are utilised, accessing a wide range of substrate solid fractions and liquid surface tensions experimentally. Wettability measurements are carried out at different azimuthal directions to exemplify the wetting/non-wetting behaviour as well as the droplet asymmetry function of both liquid composition and structure spacing. Our findings reveal that high water concentration droplets, i.e., high surface tension fluids, sit in the Cassie-Baxter regime while partial non-wetting Wenzel or mixed-mode regimes with enhanced droplet asymmetry ensuing for medium and high ethanol concentrations, i.e., low surface tension fluids, below certain micropillar spacing. Beyond micropillar spacing s ≥ 40 µm, the impact of the surface structure on the droplet shape is negligible, and droplets adopt a similar contact angle and circular shape as on a flat smooth hydrophobic surface. Wetting and non-wetting regimes are then supported by classical wetting theories and equations. A wetting regime map for a wide range of surface tension fluids and/or their mixtures on a wide domain of solid fractions is then proposed.

A review of regime maps for granulation.

Granulation, a size enlargement technique to form agglomerates of primary particles, has proven to be effective in the production of solid dosage forms. Numerous granulation techniques can be applied, such as roll compaction, drum granulation, high shear granulation, twin-screw granulation or fluid-bed granulation. If the fundamental knowledge about the granule growth mechanism, its impacts as well as their extent and proportions on the mechanism is known, a correlation of the input variables with the granule attributes paves the way regarding a granulation process design and prediction of a systems growth behaviour if one or more affecting parameters change. The dimensionless correlation of the main controlling parameters of the process physics is able to confine an operation window within which different regime areas are defined and where the influencing parameters have different implications on the final product. A regime map is created. The usage of dimensionless numbers ensures a reduction of both the experimental workload and the number of parameters that have to be considered. Thus, a scale-independent operation window can be defined. The aim of the review is a critical discussion of proposed regime maps for different granulation processes.

Influence of Hydrodynamic Conditions on the Type and Area of Occurrence of Gas-Liquid Flow Patterns in the Flow through Open-Cell Foams.

This paper reports the results of a study concerned with air-water and air-oil two-phase flow pattern analysis in the channels with open-cell metal foams. The research was conducted in a horizontal channel with an internal diameter of 0.02 m and length of 2.61 m. The analysis applied three foams with pore density equal to 20, 30 and 40 PPI (pore per inch) with porosity, typical for industrial applications, changing in the range of 92%-94%. Plug flow, slug flow, stratified flow and annular flow were observed over the ranges of gas and liquid superficial velocities of 0.031-8.840 m/s and 0.006-0.119 m/s, respectively. Churn flow, which has not yet been observed in the flow through the open-cell foams, was also recorded. The type of flow patterns is primarily affected by the hydrodynamic characteristics of the flow, including fluid properties, but not by the geometric parameters of foams. Flow patterns in the channels packed with metal foams occur in different conditions from the ones recorded for empty channels so gas-liquid flow maps developed for empty channels cannot be used to predict analyzed flows. A new gas-liquid flow pattern map for a channel packed with metal foams with the porosity of 0.92-0.94 was developed. The map is valid for liquids with a density equal to or lower than the density of water and a viscosity several times greater than that of water.

Improved Understanding of the High Shear Wet Granulation Process under the Paradigm of Quality by Design Using Salvia miltiorrhiza Granules.

BACKGROUND: High shear wet granulation (HSWG) is a shaping process for granulation that has been enhanced for application in the pharmaceutical industry. However, study of HSWG is complex and challenging due to the relatively poor understanding of HSWG, especially for sticky powder-like herbal extracts. AIM: In this study, we used Salvia miltiorrhiza granules to investigate the HSWG process across different scales using quality by design (QbD) approaches. METHODS: A Plackett-Burman experimental design was used to screen nine granulation factors in the HSWG process. Moreover, a quadratic polynomial regression model was established based on a Box-Behnken experimental design to optimize the granulation factors. In addition, the scale-up of HSWG was implemented based on a nucleation regime map approach. RESULTS: According to the Plackett-Burman experimental design, it was found that three granulation factors, including salvia ratio, binder amount, and chopper speed, significantly affected the granule size (D50) of S. miltiorrhiza in HSWG. Furthermore, the results of the Box-Behnken experimental design and validation experiment showed that the model successfully captured the quadratic polynomial relationship between granule size and the two granulation factors of salvia ratio and binder amount. At the same experiment points, granules at all scales had similar size distribution, surface morphology, and flow properties. CONCLUSIONS: These results demonstrated that rational design, screening, optimization, and scale-up of HSWG are feasible using QbD approaches. This study provides a better understanding of HSWG process under the paradigm of QbD using S. miltiorrhiza granules.

Development and evaluation of a dimensionless mechanistic pan coating model for the prediction of coated tablet appearance.

A mathematical, mechanistic tablet film-coating model has been developed for pharmaceutical pan coating systems based on the mechanisms of atomisation, tablet bed movement and droplet drying with the main purpose of predicting tablet appearance quality. Two dimensionless quantities were used to characterise the product properties and operating parameters: the dimensionless Spray Flux (relating to area coverage of the spray droplets) and the Niblett Number (relating to the time available for drying of coating droplets). The Niblett Number is the ratio between the time a droplet needs to dry under given thermodynamic conditions and the time available for the droplet while on the surface of the tablet bed. The time available for drying on the tablet bed surface is critical for appearance quality. These two dimensionless quantities were used to select process parameters for a set of 22 coating experiments, performed over a wide range of multivariate process parameters. The dimensionless Regime Map created can be used to visualise the effect of interacting process parameters on overall tablet appearance quality and defects such as picking and logo bridging.

The development of a growth regime map for a novel reverse-phase wet granulation process.

The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.

Classification of Unsteady Flow Patterns in a Rotodynamic Blood Pump: Introduction of Non-Dimensional Regime Map.

Rotodynamic blood pumps (also known as rotary or continuous flow blood pumps) are commonly evaluated in vitro under steady flow conditions. However, when these devices are used clinically as ventricular assist devices (VADs), the flow is pulsatile due to the contribution of the native heart. This study investigated the influence of this unsteady flow upon the internal hemodynamics of a centrifugal blood pump. The flow field within the median axial plane of the flow path was visualized with particle image velocimetry (PIV) using a transparent replica of the Levacor VAD. The replica was inserted in a dynamic cardiovascular simulator that synchronized the image acquisition to the cardiac cycle. As compared to steady flow, pulsatile conditions produced periodic, transient recirculation regions within the impeller and separation in the outlet diffuser. Dimensional analysis revealed that the flow characteristics could be uniquely described by the non-dimensional flow coefficient (Φ) and its time derivative ([Formula: see text]), thereby eliminating impeller speed from the experimental matrix. Four regimes within the Φ-[Formula: see text] plane were found to classify the flow patterns, well-attached or disturbed. These results and methods can be generalized to provide insights for both design and operation of rotodynamic blood pumps for safety and efficacy.