Optimisation of granola breakfast cereal manufacturing process by wet granulation and pneumatic conveying

This study has considered the optimisation of granola breakfast cereal manufacturing processes by wet granulation and pneumatic conveying. Granola is an aggregated food product used as a breakfast cereal and in cereal bars. Processing of granola involves mixing the dry ingredients (typically oats, nuts, etc.) followed by the addition of a binder which can contain honey, water and/or oil. In this work, the design and operation of two parallel wet granulation processes to produce aggregate granola products were incorporated: a) a high shear mixing granulation process followed by drying/toasting in an oven. b) a continuous fluidised bed followed by drying/toasting in an oven. In high shear granulation the influence of process parameters on key granule aggregate quality attributes such as granule size distribution and textural properties of granola were investigated. The experimental results show that the impeller rotational speed is the single most important process parameter which influences granola physical and textural properties. After that binder addition rate and wet massing time also show significant impacts on granule properties. Increasing the impeller speed and wet massing time increases the median granule size while also presenting a positive correlation with density. The combination of high impeller speed and low binder addition rate resulted in granules with the highest levels of hardness and crispness. In the fluidised bed granulation process the effect of nozzle air pressure and binder spray rate on key aggregate quality attributes were studied. The experimental results show that a decrease in nozzle air pressure leads to larger in mean granule size. The combination of lowest nozzle air pressure and lowest binder spray rate results in granules with the highest levels of hardness and crispness. Overall, the high shear granulation process led to larger, denser, less porous and stronger (less likely to break) aggregates than the fluidised bed process. The study also examined the particle breakage of granola during pneumatic conveying produced by both the high shear granulation and the fluidised bed granulation process. Products were pneumatically conveyed in a purpose built conveying rig designed to mimic product conveying and packaging. Three different conveying rig configurations were employed; a straight pipe, a rig consisting two 45° bends and one with 90° bend. Particle breakage increases with applied pressure drop, and a 90° bend pipe results in more attrition for all conveying velocities relative to other pipe geometry. Additionally for the granules produced in the high shear granulator; those produced at the highest impeller speed, while being the largest also have the lowest levels of proportional breakage while smaller granules produced at the lowest impeller speed have the highest levels of breakage. This effect clearly shows the importance of shear history (during granule production) on breakage during subsequent processing. In terms of the fluidised bed granulation, there was no single operating parameter that was deemed to have a significant effect on breakage during subsequent conveying. Finally, a simple power law breakage model based on process input parameters was developed for both manufacturing processes. It was found suitable for predicting the breakage of granola breakfast cereal at various applied air velocities using a number of pipe configurations, taking into account shear histories.

Alternative method for producing organic fertiliser from anaerobic digestion liquor and limestone powder:High Shear wet granulation

Generally, the solid and liquid fractions (digestate) from Anaerobic Digestion (AD) energy production are considered as waste. This has a negative impact on the sustainability of AD processes because of the financial outlay required to treat digestate before being discharged into municipal water treatment plants or natural water bodies. The main aim of this research was to investigate feasibility of producing an organic fertiliser using anaerobic digestate and limestone powders as the raw materials employing a high shear granulation process. Two-level factorial experimental design was used to determine the influence of granulation process variables on, the strength, resistance to attrition and yield of the granules. It was concluded from the study that it is technically feasible to produce organic fertiliser granules of acceptable strength and product yield. Increasing the liquid-to-solid ratio during granulation leads to increased granule strength and better product yield. Although the strength of the granules produced was lower than typical strength of commercial synthetic fertiliser granules (about 5 to 7. MPa), this could be improved by mixing the digestate with a polymeric binder or coating the particles post granulation. © 2012 Elsevier B.V.

EFFECT OF IMPELLER DESIGN ON PRODUCT HOMOGENIETY IN HIGH SHEAR WET GRANULATION

Design of small mixer impellers is not tailored for granulation as they are designed for a wide range of processes. The Kenwood KM070 was employed as a standard apparatus to undertake this investigation. Five different impeller designs were used, possessing different shapes and surface areas. The aim of this research was to evaluate the performances of these impellers to provide
guidance on the selection and design for the purposes of granulation. Lactose granules were produced using wet granulation with water as the binder.
The efficacy of respective granulates was measured by adding an optically
sensitive tracer.This was used to determine powder concentrations
within various regions of the granulator. It was found that impeller design influenced the homogeneity of the granules; and therefore can affect final product performance.

Effect of Impeller Design on Homogeneity, Size and Strength of Pharmaceutical Granules produced by High Shear Wet Granulation

Small mixer impeller design is not tailored for granulation because impellers are intended for a wide range of processes. The aim of this research was to evaluate the performances of several impellers to provide guidance on the selection and design for the purposes of granulation. Lactose granules were produced using wet granulation with water as a binder. A Kenwood KM070 mixer was used as a standard apparatus and five impeller designs with different shapes and surface areas were used. The efficacy of granulate formation was measured by adding an optically sensitive tracer to determine variations in active ingredient content across random samples of granules from the same size classes. It was found that impeller design influenced the homogeneity of the granules and therefore can affect final product performance. The variation in active ingredient content across granules of differing size was also investigated. The results show that small granules were more potent than larger granules.

Modelling nucleation in wet granulation

Nucleation is the first stage in any granulation process where binder liquid first comes into contact with the powder. This paper investigates the nucleation process where binder liquid is added to a fine powder with a spray nozzle. The dimensionless spray flux approach of Hapgood et al. (Powder Technol. 141 (2004) 20) is extended to account for nonuniform spray patterns and allow for overlap of nuclei granules rather than spray drops. A dimensionless nuclei distribution function which describes the effects of the design and operating parameters of the nucleation process (binder spray characteristics, the nucleation area ratio between droplets and nuclei and the powder bed velocity) on the fractional surface area coverage of nuclei on a moving powder bed is developed. From this starting point, a Monte Carlo nucleation model that simulates full nuclei size distributions as a function of the design and operating parameters that were implemented in the dimensionless nuclei distribution function is developed. The nucleation model was then used to investigate the effects of the design and operating parameters on the formed nuclei size distributions and to correlate these effects to changes of the dimensionless nuclei distribution function. Model simulations also showed that it is possible to predict nuclei size distributions beyond the drop controlled nucleation regime in Hapgood's nucleation regime map. Qualitative comparison of model simulations and experimental nucleation data showed similar shapes of the nuclei size distributions. In its current form, the nucleation model can replace the nucleation term in one-dimensional population balance models describing wet granulation processes. Implementation of more sophisticated nucleation kinetics can make the model applicable to multi-dimensional population balance models.

Scaleup of wet granulation processes: science not art

Significant advances have been made in the last decade to quantify the process of wet granulation. The attributes of product granules from the granulation process are controlled by a combination of three groups of processes occurring in the granulator: (1) wetting and nucleation, (2) growth and consolidation and (3) breakage and attrition. For the first two of these processes, the key controlling dimensionless groups are defined and regime maps are presented and validated with data from tumbling and mixer granulators. Granulation is an example of particle design. For quantitative analysis, both careful characterisation of the feed formulation and knowledge of operating parameters are required. A key thesis of this paper is that the design, scaleup and operation of granulation processes can now be considered as quantitative engineering rather than a black art. Résumé

A compartmental CFD-PBM model of high shear wet granulation

The conventional, geometrically lumped description of the physical processes inside a high shear granulator is not reliable for process design and scale-up. In this study, a compartmental Population Balance Model (PBM) with spatial dependence is developed and validated in two lab-scale high shear granulation processes using a 1.9L MiPro granulator and 4L DIOSNA granulator. The compartmental structure is built using a heuristic approach based on computational fluid dynamics (CFD) analysis, which includes the overall flow pattern, velocity and solids concentration. The constant volume Monte Carlo approach is implemented to solve the multi-compartment population balance equations. Different spatial dependent mechanisms are included in the compartmental PBM to describe granule growth. It is concluded that for both cases (low and high liquid content), the adjustment of parameters (e.g. layering, coalescence and breakage rate) can provide a quantitative prediction of the granulation process.

Evaluation of drug physical form during granulation, tabletting and storage

An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated. Despite the spectral similarities between the two drug forms, low levels of API dissociation could be quantified in the tablets; the technique allowed discrimination of around 4% of the API content as the amorphous free base (i.e. less than 1% of the tablet compression weight). API dissociation was shown to be promoted by extended exposure to moisture. Aqueous granulating fluids and manufacturing delays between granulation and drying stages and storage of the tablets in open conditions at 40◦C/75% relative humidity (RH) led to dissociation. In contrast, non-aqueous granulating fluids, with no delay in processing and storage of the tablets in either sealed containers or at lower temperature/humidity prevented detectable dissociation. It is concluded that appropriate manufacturing process and storage conditions for the finished product involved minimising exposure to moisture of the API. Analysis of the drug using FT-Raman spectroscopy allowed rapid optimisation of the process whilst offering quantitative molecular information concerning the dissociation of the drug salt to the amorphous free base form.

A population balance model for high shear granulation

In a previous paper, Hoornaert et al. (Powder Technol. 96 (1998); 116-128) presented data from granulation experiments performed in a 50 L Lodige high shear mixer. In this study that same data was simulated with a population balance model. Based on an analysis of the experimental data, the granulation process was divided into three separate stages: nucleation, induction, and coalescence growth. These three stages were then simulated separately, with promising results. it is possible to derive a kernel that fit both the induction and the coalescence growth stage. Modeling the nucleation stage proved to be more challenging due to the complex mechanism of nucleus formation. From this work some recommendations are made for the improvement of this type of model.

Process systems modelling and applications in granulation: A review

Granulation is one of the fundamental operations in particulate processing and has a very ancient history and widespread use. Much fundamental particle science has occurred in the last two decades to help understand the underlying phenomena. Yet, until recently the development of granulation systems was mostly based on popular practice. The use of process systems approaches to the integrated understanding of these operations is providing improved insight into the complex nature of the processes. Improved mathematical representations, new solution techniques and the application of the models to industrial processes are yielding better designs, improved optimisation and tighter control of these systems. The parallel development of advanced instrumentation and the use of inferential approaches provide real-time access to system parameters necessary for improvements in operation. The use of advanced models to help develop real-time plant diagnostic systems provides further evidence of the utility of process system approaches to granulation processes. This paper highlights some of those aspects of granulation. (c) 2005 Elsevier Ltd. All rights reserved.

Crystallization as a Tool for Controlling and Designing Properties of Pharmaceutical Solids

The ability to deliver the drug to the patient in a safe, efficacious and cost-effective manner depends largely on the physicochemical properties of the active pharmaceutical ingredient (API) in the solid state. In this context, crystallization is of critical importance in pharmaceutical industry, as it defines physical and powder properties of crystalline APIs. An improved knowledge of the various aspects of crystallization process is therefore needed. The overall goal of this thesis was to gain better understanding of the relationships between crystallization, solid-state form and properties of pharmaceutical solids with a focus on a crystal engineering approach to design technological properties of APIs. Specifically, solid-state properties of the crystalline forms of the model APIs, erythromycin A and baclofen, and the influence of solvent on their crystallization behavior were investigated. In addition, the physical phenomena associated with wet granulation and hot-melting processing of the model APIs were examined at the molecular level. Finally, the effect of crystal habit modification of a model API on its tabletting properties was evaluated. The thesis enabled the understanding of the relationship between the crystalline forms of the model APIs, which is of practical importance for solid-state control during processing and storage. Moreover, a new crystalline form, baclofen monohydrate, was discovered and characterized. Upon polymorph screening, erythromycin A demonstrated high solvate-forming propensity thus emphasizing the need for careful control of the solvent effects during formulation. The solvent compositions that yield the desirable crystalline form of erythromycin A were defined. Furthermore, new examples on solvent-mediated phase transformations taking place during wet granulation of baclofen and hot-melt processing of erythromycin A dihydrate with PEG 6000 are reported. Since solvent-mediated phase transformations involve the crystallization of a stable phase and hence affect the dissolution kinetics and possibly absorption of the API these transformations must be well documented. Finally, a controlled-crystallization method utilizing HPMC as a crystal habit modifier was developed for erythromycin A dihydrate. The crystals with modified habit were shown to posses improved compaction properties as compared with those of unmodified crystals. This result supports the idea of morphological crystal engineering as a tool for designing technological properties of APIs and is of utmost practical interest.

Solubility and physical stability improvement of natiral xanthine derivatives

Use of natural xanthine derivates in medicine is complicated with their physical properties. Theobromine is poorly soluble while theophylline is highly sensitive to hydration. The aim of this study was to improve bioavailability of xanthines by co-crystallization, theophylline was also cocrystallized with carboxylic acids (capric, citric, glutaric, malenic, malonic, oxalic, stearic, succinic) and HPMC. Co-crystallization was performed by slow evaporation and ball milling. Physical stability was checked by wet granulation and water sorption methods, solubility was measured by intrinsic tablet dissolution. Theobromine formed co-crystal with other xanthines and theophylline interacted with all acids except stearic and HPMC, the latter showed alternative interactions based on hydrogen bonding. Hydration resistance was good in theophylline:succinic acid co-crystal and excellent in complexes containing capric, stearic acids and HPMC. Theophylline:HPMC showed improved solubility. The reported approach can promote use of xanthines and can be recommended for other compounds with similar problems.

Selection of operational parameters for the production of instant soy protein isolate by pulsed fluid bed agglomeration

The objective of this study was to select the optimal operational conditions for the production of instant soy protein isolate (SPI) by pulsed fluid bed agglomeration. The spray-dried SPI was characterized as being a cohesive powder, presenting cracks and channeling formation during its fluidization (Geldart type A). The process was carried out in a pulsed fluid bed, and aqueous maltodextrin solution was used as liquid binder. Air pulsation, at a frequency of 600 rpm, was used to fluidize the cohesive SPI particles and to allow agglomeration to occur. Seventeen tests were performed according to a central composite design. Independent variables were (i) feed flow rate (0.5-3.5 g/min), (ii) atomizing air pressure (0.5-1.5 bar) and (iii) binder concentration (10-50%). Mean particle diameter, process yield and product moisture were analyzed as responses. Surface response analysis led to the selection of optimal operational parameters, following which larger granules with low moisture content and high process yield were produced. Product transformations were also evaluated by the analysis of size distribution, flowability, cohesiveness and wettability. When compared to raw material, agglomerated particles were more porous and had a more irregular shape, presenting a wetting time decrease, free-flow improvement and cohesiveness reduction. (C) 2010 Elsevier B.V. All rights reserved.