An interaction-based mixing model for predicting porosity and tensile strength of directly compressed ternary blends of pharmaceutical powders.

Predicting the mechanical properties of powder mixtures without extensive experimentation is important for model driven design in solid dosage form manufacture. Here, a new binary interaction-based model is proposed for predicting the compressibility and compactability of directly compressed pharmaceutical powder mixtures based on the mixture composition. The model is validated using blends of MCC, lactose and paracetamol or ibuprofen.

Mechanistic modeling of twin screw wet granulation for pharmaceutical formulations: Calibration, sensitivity analysis, and model-driven workflow.

Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in pharmaceutical manufacturing. In this study, a mechanistic-based population balance model is applied to twin screw wet granulation. This model incorporated a recently developed breakage kernel specifically designed for twin screw granulation, along with nucleation, layering, and consolidation.

A novel mixing rule model to predict the flowability of directly compressed pharmaceutical blends.

In the pharmaceutical industry, powder flowability is an essential manufacturability attribute to consider when selecting the suitable manufacturing route and formulation. The selection of the formulation is usually based on the physical and chemical properties of the Active Pharmaceutical Ingredient (API) under consideration. Current industrial practice heavily relies on experimental work, which often results in significant labor and API consumption that results in higher costs.

Modelling the effect of L/S ratio and granule moisture content on the compaction properties in continuous manufacturing.

The pharmaceutical field is currently moving towards continuous manufacturing pursuing reduced waste, consistency, and automation. During continuous manufacturing, it is important to understand how both operating conditions and material properties throughout the process affect the final properties of the product to optimise and control production. In this study of a continuous wet granulation line, the liquid to solid ratio (L/S) and drying times were varied to investigate the effect of the final granule moisture content and the liquid to solid ratio on the properties of the granules during tabletting and the final tensile strength of the tablets.

Model driven design for integrated twin screw granulator and fluid bed dryer via flowsheet modelling.

This paper presents a flowsheet modelling of an integrated twin screw granulation (TSG) and fluid bed dryer (FBD) process using a Model Driven Design (MDD) approach. The MDD approach is featured by appropriate process models and efficient model calibration workflow to ensure the product quality. The design space exploration is driven by the physics of the process instead of extensive experimental trials.

Is a female physical empowerment campaign effective in improving positive body image, motivation for physical activity, and physical activity behavior in young female adults? A two-study experimental test of "This Girl Can".

This Girl Can is a campaign designed to empower women to increase physical activity. The campaign uses images/videos of women of diverse body weights/shapes, ages and ethnicities being physically active, emphasizing body functionality. First, we examined the effects of multi-session (N = 3) exposures to This Girl Can on body functionality, body appreciation and self-compassion (Study 1).

Exploring the role of crystal habit in the Ostwald rule of stages.

The crystallization of calcium carbonate is shown to be dictated by the Ostwald rule of stages (ORS), for high relative initial supersaturations ( ), under sweet (carbon dioxide saturated) and anoxic (oxygen depleted) solution conditions. Rhombohedral calcite crystals emerge after the sequential crystallization and dissolution of the metastable polymorphs: vaterite (snowflake-shaped) and aragonite (needle-shaped). However, the presence of certain cations, which can form trigonal carbonates (e.

Τhe role of surface energy in the apparent solubility of two different calcite crystal habits.

The interplay between polymorphism and facet-specific surface energy on the dissolution of crystals is examined in this work. It is shown that, using cationic additives, it is possible to produce star-shaped calcite crystals at very high supersaturations. In crystallization processes following the Ostwald rule of stages these star-shaped crystals appear to have higher solubility than both their rhombohedral counterparts and needle-shaped aragonite crystals.

Tableting model assessment of porosity and tensile strength using a continuous wet granulation route.

This paper presents a comprehensive assessment of the most widely used tablet compaction models in a continuous wet granulation tableting process. The porosity models, tensile strength models and lubricant models are reviewed from the literature and classified based on their formulations i.e.

Model driven design for twin screw granulation using mechanistic-based population balance model.

This paper presents a generic framework of Model Driven Design (MDD) with its application for a twin screw granulation process using a mechanistic-based population balance model (PBM). The process kernels including nucleation, breakage, layering and consolidation are defined in the PBM. A recently developed breakage kernel is used with key physics incorporated in the model formulation.

Roller compaction: Infrared thermography as a PAT for monitoring powder flow from feeding to compaction zone.

Roller compaction is a continuous dry granulation process, in which powder is compressed by two counter-rotating rollers. During this process, the powder feeding to the compaction zone has a significant effect on product quality. This work investigates the flow of powder from the feeding zone to the compaction zone using online infrared thermography as Process Analytical Technology (PAT) which is achieved via a specially built cheek plate (side-sealing).

Application of feeding guiders to improve the powder distribution in the two scales of roller compactors.

Roller compaction is a continuous dry granulation process, where the powder is compressed between two counter-rotating rollers and compacted into ribbons. The quality and homogeneity of the granulate is determined by the uniformity and porosity of the ribbon, which depends on the feeding process of the primary powder to the rollers, the flow properties of the primary powder and process parameters such as roller forces. Previous work was conducted to improve the powder flow and distribution in the feeding zone by developing new feeding guiders, which are located in the feeding zone close to the rollers on the lab-scale roller compactor Alexanderwerk WP120 Pharma (Yu et al.

Characteristics of multi-component formulation granules formed using distributive mixing elements in twin screw granulation.

This work examines the influence of pharmaceutical powder formulation characteristics on granule properties formed using distributive mixing elements (DMEs) in twin screw granulation. High and low drug dose formulations with three different active pharmaceutical ingredients (APIs) were considered. The type and concentration of the API in the formulation significantly affected the dry blend particle size distribution and the wet blend dynamic yield strength.

Assessment of Intragranular and Extragranular Fracture in the Development of Tablet Tensile Strength.

When a tablet is compacted from deformable granules and then broken, the fracture plane may cleave granules in 2 (intragranular fracture) or separate neighboring granules (extragranular fracture). In this study, a novel method was developed to quantify the extent of intragranular versus extragranular fracture by compacting tablets from multicolored ideal granules and evaluating fracture surfaces. The proportions of intragranular and extragranular fracture were quantified and modeled in light of a new metric; the deformation potential, Δ, reflecting the solid fraction increase as an initial granule bed is compressed into a final tablet.

Improving feeding powder distribution to the compaction zone in the roller compaction.

In the roller compaction process, powder flow properties have a significant influence on the uniformity of the ribbon properties. The objective of this work was to improve the powder flow in the feeding zone by developing novel feeding guiders which are located in the feeding zone close to the rollers in the roller compactor (side sealing system). Three novel feeding guiders were designed by 3D printing and used in the roller compactor, aiming to control the amount of powder passing across the roller width.

Statistical analysis and comparison of a continuous high shear granulator with a twin screw granulator: Effect of process parameters on critical granule attributes and granulation mechanisms.

This study is concerned with identifying the design space of two different continuous granulators and their respective granulation mechanisms. Performance of a continuous high shear granulator and a twin screw granulator with paracetamol formulations were examined by face-centered cubic design, which focused on investigating key performance metrics, namely, granule size, porosity, flowability and particle morphology of granules as a function of essential input process parameters (liquid content, throughput and rotation speed). Liquid and residence time distribution tests were also performed to gain insights into the liquid-powder mixing and flow behavior.

Investigation of an 11mm diameter twin screw granulator: Screw element performance and in-line monitoring via image analysis.

As twin screw granulation (TSG) provides one with many screw element options, characterization of each screw element is crucial in optimizing the screw configuration in order to obtain desired granule attributes. In this study, the performance of two different screw elements - distributive feed screws and kneading elements - was studied in an 11 mm TSG at different liquid-to-solid (L/S) ratios. The kneading element configuration was found to break large granules more efficiently, leading to narrower granule size distributions.

Effect of relative humidity on onset of capillary forces for rough surfaces.

Atomic force microscopy (AFM) was used to investigate the effect of relative humidity (RH) on the adhesion forces between silicon nitride AFM probes, hydrophilic stainless steel, and hydrophobic Perspex® (polymethylmethacrylate, PMMA). In addition, AFM-based phase contrast imaging was used to quantify the amount and location of adsorbed water present on these substrates at RH levels ranging from 15% to 65% at 22°C. Both the adhesion forces and the quantities of adsorbed moisture were seen to vary with RH, and the nature of this variation depended on the hydrophobicity of the substrate.

Osmotic second virial cross-coefficient measurements for binary combination of lysozyme, ovalbumin, and α-amylase in salt solutions.

Interactions measurement is a valuable tool to predict equilibrium phase separation of a desired protein in the presence of unwanted macromolecules. In this study, cross-interactions were measured as the osmotic second virial cross-coefficients (B23 ) for the three binary protein systems involving lysozyme, ovalbumin, and α-amylase in salt solutions (sodium chloride and ammonium sulfate). They were correlated with solubility for the binary protein mixtures.

Modeling the granule formation mechanism from single drop impact on a powder bed.

Granule formation from drop impact on a powder bed can occur by either Tunneling or Spreading/Crater Formation. The governing regime can be specified by the experimentally determined modified Bond number (Bo(g)*), which is a ratio of the capillary force to the gravitational force acting on a particle. It was hypothesized that Tunneling would occur when the capillary and surface tension forces exceeded the weight of a powder aggregate in contact with the drop.

Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy.

Three different approaches have been evaluated for monitoring ribbon density through real-time near-infrared spectroscopy measurements. The roll compactor was operated to produce microcrystalline cellulose (MCC) ribbons of varying densities. The first approach used the slope of the spectra which showed a variation through the ribbon that could be attributed to density.

Correlation of second virial coefficient with solubility for proteins in salt solutions.

In this work, osmotic second virial coefficients (B(22)) were determined and correlated with the measured solubilities for the proteins, α-amylase, ovalbumin, and lysozyme. The B(22) values and solubilities were determined in similar solution conditions using two salts, sodium chloride and ammonium sulfate in an acidic pH range. An overall decrease in the solubility of the proteins (salting out) was observed at high concentrations of ammonium sulfate and sodium chloride solutions.

A priori performance prediction in pharmaceutical wet granulation: testing the applicability of the nucleation regime map to a formulation with a broad size distribution and dry binder addition.

In this study, Hapgood's nucleation regime map (Hapgood et al., 2003) was tested for a formulation that consists of an active pharmaceutical ingredient (API) of broad size distribution and a fine dry binder. Gabapentin was used as the API and hydroxypropyl cellulose (HPC) as the dry binder with deionized water as the liquid binder.

Effect of particle properties on the flowability of ibuprofen powders.

Powder flowability is one of the key parameters in the pharmaceutical tabletting process. The flowability is affected by both the particles' properties and the tabletting equipment characteristics. Although it is generally accepted that powder flowability increases with an increase in particle size, quantitative studies and comprehensive theoretical insights into the particle property effects are still lacking.