Top Spray Research Articles

Tobacco stalk nanofibrillated cellulose: An eco-friendly binder on fluidized bed granulation

The search for new excipients that provide formulation alternatives over existing ones and that are derived from natural resources has advanced over the years. Emerging from this scenario, an important alternative to traditional excipients is nanofibrillated cellulose (NFC), which is generally obtained from agricultural wastes and is a cellulose-rich material. Most of the time, the nanofibers are presented in aqueous dispersions that form a highly entangled network of fibrous particles that exhibit gel-like behavior. Therefore, the present work aimed to explore the gel-like behavior of NFC from tobacco stalks to evaluate it as a binder in a fluid bed granulation process for further application as a pharmaceutical ingredient. The granulation process was carried out using top spray mode with an inlet air temperature of 80 °C, airflow between 9 and 11 mm3 h−1, and atomizing air pressure of 0.7 bar. Povidone (PVP) was used as a standard binder for comparison purposes. The binder systems were sprayed on the powder blend of theophylline and maltodextrin at a feed rate of 3.05 mL⋅min−1. Granule properties, such as yield, moisture content, morphology, label-free Raman imaging, particle size distribution, drug content, and flow properties, were evaluated. The process using NFC provided granules with excellent drug uniformity, low moisture content (<2 %), high yield (>92 %), and passable flow properties. Their behavior was comparable to that of granules prepared with the classical PVP binder system. Therefore, this study opens a perspective for the reuse of NFC from tobacco stalk, an agricultural waste, as an alternative binder for the granulation process, contributing to environmental sustainability.

Formulation and Evaluation of Guaifenesin Gastro Retentive Tablets

Guaifenesin is an expectorant and belongs to BCS class I which exhibits high solubility and high permeability. Guaifenesin has a half-life of 1 hour; in order to increase its duration of action gastroretentive tablets are formulated. Guaifenesin shows poor flow properties so the method opted for the preparation of this tablets is Top spray granulation. In which HPMC K100LV/HPMC E6LV/HPMC K100M/HPMC K15MPCR is used as swelling matrix polymer, Povidone is used as binder, Magnesium stearate is used as lubricant and MCC is used as diluent. Tablets are evaluated for floating lag time, total floating time, thickness, hardness, friability and invitro drug release studies were performed. The optimized formulation showed less floating lag time, sufficient floating time and with maximum drug release of 88.9% at the end of 12 hours.

Test data analysis of the thermodynamic vent system-augmented top spray injector liquid nitrogen transfer experiments

Traditionally, a cryogenic tank must be pre-chilled to some “target” temperature before the main vent valve can be closed to attempt a non-vented fill (NVF) of cryogenic liquid propellant. This methodology is particularly attractive for performing in-space transfer of cryogens due to the unknown location of the liquid/vapor interface in microgravity and the high likelihood of venting liquid if the vent valve is opened during transfer. This paper presents in-depth test data analysis of a Thermodynamic Vent System (TVS) augmented injector used for cryogenic tank chilldown and fill experiments of a thin-walled Titanium tank. Eight tests were conducted using liquid nitrogen across a range of inlet conditions and boundary conditions, and three different chilldown/fill methods. For four of the tests, the injector sprays liquid into the tank as normal, but also uses a TVS heat exchanger to cool the metallic injector itself as well as the main incoming liquid stream. Results show that using the TVS augmented injector simplifies transfer operation via enhanced condensation at the injector surface at the cost of sacrificing only a small amount of propellant.

Dynamic modeling and analysis of bunkering and pressurization for marine LNG fuel tank

Liquefied natural gas (LNG) is becoming an ideal alternative fuel for vessels because of its environmental and economic advantages. As LNG is a cryogenic fuel stored around -163 °C, the LNG fuel tank is a highly non-equilibrium thermodynamic system especially during bunkering and pressurization processes. The accurate prediction of the thermodynamic behaviors inside the LNG fuel tank is critical for the system design and operation. In this study, a fast and effective analytical model of bunkering and pressurization for marine LNG fuel tank was developed. The Norwegian car ferry MF Korsfjord was chosen as a benchmark case to confirm the validity of the model. The top spray filling process, the pressurization process, and the fuel gas supply process of the MF Korsfjord were simulated. The model prediction showed good agreement with the measured data. Besides, cryogenic liquid sloshing inside the fuel tank was investigated as well. The results showed that the sloshing had a severe impact on the tank pressure, especially when the resonance condition of the tank was met, resulting in the shutdown of gas engines in extreme situations.

Formulation Development and Evaluation of Taste Masked Anthelmintics Chewable Tablets by Using Fluid Bed Processor Technique

Human helminthic infections are prevalent and have serious world health consequences. Praziquantel is frequently recommended anthelmintic therapy provided in tablet form for the oral treatment of schistosome infections. The goal of this study is to create and analyze a patient-friendly flavor masked anthelmintics chewable tablet of Praziquantel using Eudragit® EPO using a "granules coating technology" using a Fluid Bed Processor GPCG 1.1. (Top Spray). This strategy is better as compared to coating of Praziquantel granules with Eudragit EPO in Rapid Mixer Granulator. Due to its limited water solubility, the formulation disintegrates and dissolves slowly at high pH. Drug release was &gt;98% in 60 min. The key excipient in chewable tablets incorporate flavor enhancing agent and sweetening agent. By using wet granulation process the tablet are prepared. Chewable tablets are evaluated by chemical and physical evaluation methods. Physical methods and chemical method include appearance, hardness, friability, disintegration, dissolution, drug content, dosage uniformity, accelerated stability studies, and sensory evaluation.

Fluidized Bed Processing: Versatile Technique in Dosage form Development

Fluidized bed processor is the popular and successful technique widely being in pharmaceutical industries. Fluidized bed processor was developed in 1950. In this paper, the information about principal, spraying techniques of fluidized bed processor and recent applications of FBP in pharmaceutical industries were reviewed. In face, it is more often than not the last step in the manufacturing process. The fluid bed system has a bed of solid discrete particle which are fluidized upward by passing a stream of air through a perforated sheet. The air is heated and the process hot air evaporate the fluid and dries the solid. There are three types of spraying techniques, the top spray commonly applicable for formation of granules to improve the flow characteristics of powder. The bottom spray is required for optimal application of coating material to the particle and achieves desire drying. The tangential spray used to ensure homogenous granulation. This insures good product at a lower cost than traditional drying methods. For instance, low moisture content in the polymer product is a prerequisite for subsequent extrusion processes. The main applications of fluidized bed processor, such as pelletization, particle coating, granulation powder and drying. This technology commonly employed for formed granules for tableting, capsule, excellent solubility, dust free process, fee flow properties, good dispensability due to porous structure.

Heat transfer characterization under radial jet and falling film induced rewetting

Abstract Empirical correlations are developed for rewetting velocity and maximum heat transfer coefficient during rewetting phase of single hot vertical Fuel Pin Simulator (FPS) by using radial jet impingement and falling film. Emergency Core Cooling System (ECCS) has been designed for Advance Heavy water Reactor (AHWR) to rewet the hot fuel pin under the loss of coolant accident. Coolant injection takes place from a water rod which is located at the center of the fuel bundle in form of jets to rewet hot surface of fuel pin under loss of coolant accident. This kind of design to reflood the fuel bundle is different than bottom and top spray reflooding practiced in PWR and BWR type of nuclear reactors. There are two different kinds of rewetting found during radial jet induced cooling. The first one is due to radial jet impingement and the second one is due to falling film which is below the jet impingement point. Rewetting velocity has been predicted along the length of fuel pin due to radial jet impingement cooling. Temperature of FPS has been varied from 400°C to 700°C with help of different powers supply, simulating decay heat of reactor. A variation of coolant radial jet mass flow rate is from 0.5 lpm to 1.8 lpm. It is considered during ECCS injection. It has been observed from the experiments that rewetting velocity decreases with increasing the clad surface temperature and increases with increasing the coolant mass flow rate. The rewetting velocity in falling film is found to be nearly 1.8 times higher than rewetting velocity predicted in circumferential direction. Further, it is found that maximum heat transfer coefficient increases with increasing the radial jet coolant mass flow rate. The maximum heat transfer coefficient in case of radial jet impingement is found to be nearly 1.5 times the falling film rewetting. Developed correlation predicts the maximum heat transfer coefficient with experimental data well within the error band of ±10%.

Modeling, simulation and analysis of tank thermodynamic behaviors during no-vent LNG bunkering operations

The bunkering process is an important issue of the operation of liquefied natural gas (LNG) fueled ships. In this paper, an analytical model was developed to predict and investigate the thermodynamic behaviors of marine LNG fuel tanks during no-vent bunkering operations. The complex heat and mass transfer phenomena inside the cryogenic tanks were considered and modeled. A spray droplet model was developed to quantitatively evaluate the vapor condensation and cooling effect in the tank during top spray filling. The validity of the model was confirmed by the measured data on a Norwegian car ferry. The results show that the vapor condensation and cooling at the droplet-vapor interface dominate the top spray filling process, while the vapor compression dominates the bottom filling process. The impact of vapor condensation on the tank pressure during top spray filling is around 2.6 times as large as the vapor cooling. Furthermore, parametric study reveals that the bunkering performance is very sensitive to the LNG supply temperature and droplet diameter.

Taste Masking of Granulated Acetaminophen by Water Insoluble Ethylcellulose Coating.

Bitter tasting of drugs leads to non-compliance especially in the case of pediatric patients due to their inability to swal-low medication. In this study, we aimed to mask the bitter taste of acetaminophen (APAP) particles through coating. A pH independent water insoluble ethylcellulose polymer was used to coat the APAP. The coating of water insoluble ethylcellulose on APAP can have a significant impact on the dissolution profile. Various grades of APAP were used for coating; fine grade, Compap L90% having wide particle size distribution (PSD), and a special granular (SG) APAP 1680 having narrow PSD. Coating was performed using top spray (Vector) for Compap L90% and SG APAP 1680 grade of APAP. Bitter taste of SG APAP was masked after spraying dispersion equivalent to a weight gain of 10% compared to 35% used for Compap L90%. Using bottom spray (Wurster coater, GPCP 2.0), coating was performed on SG APAP 1680 grade of APAP by spraying aqueous dispersion of ethylcellulose (Surelease) equivalent to a weight gain of 10%. The scalability of the top spray process was also evaluated in GPCG 30 and bitter taste was masked by using Surelease dispersion equivalent to a weight gain of 6%. Coated APAP was examined for particle size (PS), particle size distribution (PSD), flowability, and drug release profile. Dissolution was performed using USP apparatus 2 and 4 in phosphate buffer and evaluated for mechanism of drug release. Particle size obtained for coated SG APAP 1680 via top and bottom spray process was 404 µm d(90) and 487 µm d(90) respectively. The results of the study demonstrated the potential of Surelease dispersion in taste masking. The use of SG APAP 1680 having narrow PSD allowed taste masking to achieve at low weight gain without greatly affecting the dissolution profile.

Pharmaceutical nanoparticle isolation using CO2-assisted dynamic bed coating.

Poor solubility of new chemical entities (NCEs) is a major bottleneck in the pharmaceutical industry which typically leads to poor drug bioavailability and efficacy. Nanotechnologies offer an interesting route to improve the apparent solubility and dissolution rate of pharmaceutical drugs, and processes such as nano-spray drying and supercritical CO2-assisted spray drying (SASD) provide a route to engineer and produce solid drug nanoparticles. However, dried nanoparticles often show poor rheological properties (e.g. flowability, tabletability) and their isolation using these methods is typically inefficient and leads to poor collection yields. The work presented herein demonstrates a novel production and isolation method for drug nanoparticles using a 'top spray dynamic bed coating' process, which uses CO2 spray as the fluidizing gas. Nanoparticles of three BCS class II Active Pharmaceutical Ingredients (APIs), namely carbamazepine (CBZ), ketoprofen (KET) and risperidone (RIS), were produced and successfully coated onto micron-sized microcrystalline cellulose (MCC) particles. The size distribution of the API nanoparticles was in the range of 90-490nm. The stable forms of CBZ (form III), KET (form I), and the metastable form of RIS (form B) were produced and coated onto MCC carrier microparticles. All the isolated solids presented optimal rheological properties along with a 2-6 fold improvement in the dissolution rate of the corresponding APIs. Hence, the 'top spray dynamic bed coater' developed in this work demonstrates to be an efficient approach to produce and coat API nanoparticles onto carrier particles with optimal rheological properties and improved dissolution.

Hydrodynamics and heat transfer in a fluidized bed with liquid spray: Particle color-change based measurement and modelling

Fluidized beds with the liquid spray have been widely applied due to efficient heat transfer ability. In this work, the liquid-containing particles and the liquid dispersion pathway are visualized by a unique reversible thermochromic material (RTM) tracking method. The effects of evaporative liquid considering different nozzle modes on bubble density, particle motion and heat transfer are investigated combining PIV and DIA. The results indicate that the liquid injection decreases particle fluctuation and promotes bubble generation. A stable liquid-containing zone is observed under the top spray mode, whereas liquid disperses rapidly under the side-wall spray mode. A multi-zone heat transfer model (MHTM) is then developed based on the bubble growth and inter-layer exchange models. Experimental and calculated temperature profiles indicate that the side-wall spray mode leads to larger temperature differences. The methods proposed can be applied for the analysis of the complex multiphase system and optimization of the nozzle configuration.

Evaluation of powder-layering vs. spray-coating techniques in the manufacturing of a swellable/erodible pulsatile delivery system

A swellable/erodible system for oral time-dependent release, demonstrated to provide consistent pulsatile and colonic delivery performance, has been manufactured through a range of coating techniques to achieve the functional hydroxypropyl methylcellulose (HPMC) layer. Although aqueous spray-coating has long been preferred, the processing times and yields still represent open issues, especially in view of the considerable amount of polymer required to give in vivo lag phases of proper duration. To make manufacturing of the delivery system more cost-efficient, different coating modes were thus evaluated, namely top and tangential spray-coating as well as powder-layering, using a fluid bed equipment. To this aim, disintegrating tablets of 5 mm in diameter, containing a tracer drug, were coated up to 50% weight gain with low-viscosity HPMC, either as a water solution or as a powder formulation. In all cases, process feasibility was assessed following setup of the operating conditions. Irrespective of the technique employed, the resulting dosage forms exhibited uniform coating layers able to defer the onset of release as a function of the amount of polymer applied. The structure and thickness of such layers differed depending on the deposition modes. With respect to top spray-, both tangential spray-coating and powder-layering were shown to remarkably ameliorate the process time, which was reduced to approximately 1/3 and 1/6, and to enhance the yield by almost 20 and 30%, respectively. Clear advantages associated with such techniques were thus highlighted, particularly with respect to powder-layering here newly proposed for application of a swellable hydrophilic cellulose derivative.

Modelling of urea aggregation efficiency via particle tracking velocimetry in fluidized bed granulation

This work presents a predictive model to estimate the particle size distribution (PSD) and aggregation efficiency of wet granulation of urea in top spray fluidized bed. To elucidate the model solution, the experimental granulation process of urea particles was performed. Urea particles with an average size of 250 µm, were charged and fluidized at the granulator by spraying a binder solution. Urea granule samples were withdrawn at different granulation time, and the respective particle size distributions were characterized using the sieving method. An empirical model for aggregation rate constant has been developed based on the experimental data at various operating conditions and used in population balance model to estimate the PSD. Furthermore, the model has been extended to determine aggregation efficiency using particle tracking velocimetry method (PTV). The developed model could be employed to estimate the urea granulation performance and kinetics in fluidized bed for design and scale-up purpose.

DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS OF MEMANTINE HYDROCHLORIDE-A REMEDY FOR ALZHEIMER’S DISEASE

Objective: The study is directed towards the development of an orally disintegrating drug delivery system of memantine hydrochloride which can be commercially exploited for the well-being of society for the treatment of Alzheimer’s disease, which is a most common form of dementia.&#x0D; Methods: Orally disintegrating immediate-release tablets of memantine hydrochloride were prepared and optimized for disintegration time and in vitro drug release. The top spray granulation method was used for the preparation of granules. Subsequently, these granules were compressed to tablets. The levels of diluent, disintegrant and taste-masking agents were optimized using the design of experiments. The resulting tablets were evaluated for disintegration time and in vitro drug release. The optimized formulation was subjected to accelerated stability study for 3 mo.&#x0D; Results: The optimized orally disintegrating tablet formulation exhibited a disintegration time of 2-3 min and complete drug release i.e. more than 85 % drug release within 10 min while performing in vitro drug release study. This is a prerequisite for faster action in the case of patients suffering from Alzheimer’s disease. Accelerated stability studies indicated good physical and chemical stability of the optimized formulation.&#x0D; Conclusion: Developed orally disintegrating tablet formulation of memantine hydrochloride could release the drug faster compared to conventional immediate-release tablets which is useful in paediatric, geriatric and psychiatric patients.

Development and verification of a novel design space and improved scale-up procedure for fluid bed granulation using a mechanistic model

A mechanistic model has been developed for scale-up of batch fluid bed (top spray) granulation, leading to a design space which was verified against experimental data at pilot-plant and commercial scales. Current published models fail to give reliable scale-up. The process is very sensitive to operating conditions, and intermittent spray and air flow during filter bag shaking is shown to substantially affect moisture content and the final granule properties. Three parameters (inlet air temperature, flow rate and humidity) are consolidated into a composite parameter Qair which, in combination with solution spray rate msol, gives a two-dimensional design space which is typically trapezoidal. Peak moisture content influences final granule attributes and depends on the ratio Qair/msol. Scale-up and product transfer between different equipment are predicted. The model has been applied to an actual pharmaceutical product, achieving robust product quality at commercial scale, and incorporated into a successful regulatory filing submission.

Simultaneous wetting and drying: Fluid bed granulation and tablet film coating

Simultaneous wetting and drying occur in processes such as fluid bed (top spray) granulation, Wurster coating, and tablet film coating. Modeling shows that the spraying and evaporation processes must be carefully balanced and the operating window may be significantly narrower than for standalone drying processes, giving control challenges. Effective scale-up and operational strategies are developed. Intermittent spray and air flow during filter bag shaking can have a major effect. The design space for fluid bed granulation is heat balance controlled while that for coating is rate controlled. Both can be non-orthogonal and this has been accepted by pharmaceutical regulatory authorities.

CFD–DEM–PBM coupled model development and validation of a 3D top-spray fluidized bed wet granulation process

In pharmaceutical manufacturing, fluidized bed granulation is one of the common processing options available to achieve better flowability of powders through size enlargement of primary particles. In fact over the last 50 years, various fluidized bed operations including freezing, drying, impregnation, coating, etc. have become a common place in the chemical processing industry due to the high level of contacts between fluids and solids attainable in a fluid bed system. These complex interactions between the fluid and particles also mean that simulating fluidized beds are still a challenging endeavor. Generally, Computational Fluid Dynamics (CFD) packages are employed to model the pressure drops in fluids; however, the presence of high concentration of solids and the complexity of granulation behavior require more advanced particle models than are available with CFD software. As a result, coupled frameworks that utilize the strength of particulate simulations such as Discrete Element Method (DEM) and bulk granulation modeling such as Population Balance Model (PBM) in conjunction with CFD information are the next steps to developing practical fluid bed granulation models.This paper aims to provide a comprehensive description of the development and validation of a coupled CFD–DEM–PBM framework for a fluidized bed wet granulation operation. A two-way coupled CFD–DEM model is developed for a 3-dimensional, lab-scale, top spray fluid bed granulator to study the effects of process parameters such as inlet air flow rate and inlet air temperature on the particle flow dynamics and the residence time in the spray zone. A one-way transfer of data from CFD–DEM to PBM is then applied to relate the effects of particle-fluid interactions to granulation behavior occurring within the fluidized bed system. Mechanistic rate expressions were developed in the PBM to create links between CFD–DEM results and PBM rate kernels which can express the effect of critical process parameters (CPPs) such as air flow rate, inlet air temperature, binder spray rate, etc. to experimentally measured critical quality attributes (CQAs) including granule size distribution and liquid content values. From comparison with experimental results, the framework presented shows good accuracy at capturing the dynamics of the system. The presented framework demonstrates a practical process model development methodology by efficiently coupling multi-phase simulation techniques which can be used for effective process design, development and scale-up purposes.

Two-compartment modeling and dynamics of top-sprayed fluidized bed granulator

• Compartmental approach is used to model and simulate a top sprayed fluidized bed granulator. • The dynamic behavior is analysed by varying the process conditions and parameters. • Finite volume scheme is modified to solve the proposed mathematical model. • New analytical solutions are derived for the verification of model. • Constant volume Monte Carlo is developed for the proposed model and used for the validation. A top Spray Fluidized Bed Granulator (SFBG) is being modeled and analyzed with the help of population balance equation (PBE) and analytical as well as numerical results. The mathematical model for SFBG is derived using the concept of compartment modeling. The granulator is divided into two compartments, a wet compartment in which aggregation is the dominant process, and a dry compartment that is dominated by breakage. A new discretization is given to solve the model which is based on the idea of conserving the important properties of the system. The numerical results of the moments derived by the new discretization are validated against the developed exact results for different combinations of the aggregation and breakage kernels. The model is also tested for physical tractable kernel and the numerical results are authenticated with the results of constant volume Monte Carlo. The two-compartment model is shown to behave dynamically in a distinctly different manner to the simpler one-compartment model. The most critical parameter is the exchange flow between the compartments. When the characteristic time for this flow is low relative to the rates of aggregation and breakage, the effect of breakage is amplified disproportionally relative to breakage, and whereas the single-compartment granulator always reaches steady state between the rates of aggregation and breakage, the two-compartment model may, under some conditions, lead to continuously decreasing size under the dominance of breakage.

The Effect of Pretreatment (Spray Drying) on the Yield and Selected Nutritional Components of Whole Camel Milk Powder

The effect of spray drying on the composition of camel milk powder was evaluated. A full factorial experimental design was used to see the effects of inlet temperature (160 °C, 140 °C, and 120 °C), atomization pressure (800, 600, and 400 bar) and feed flow rate (5, 4, and 3 rev/s) on cyclone and vitamin C recoveries. Principal components analysis (PCA) was used to check classification of spray dried whole camel milk powders based on their processing conditions and multiple correspondence analysis (MCA) on the fatty acid profiles. The average proximate composition of the camel milk viz., fat, protein, lactose, and total solid were 3.0%, 3.21%, 3.01%, and 10.29% respectively. The powder yield (cyclone recovery) increased with increasing inlet temperature and decreasing feed flow rate. High outlet temperature and pressure decreased vitamin C recovery. As a result of PCA of the camel milk powders, they were classified into high heat treated and low heat treated milk powders while the MCA of the fatty acid profiles of camel milk powders were classified into high pressure and low pressure treated powders and it was concluded that higher atomization pressure caused increase in the content of fatty acids. PRACTICAL APPLICATION: Drying of camel milk (using spray drying) can extend its shelf life. The spray drying process must be optimized in order to retain the nutritional properties of the milk and the techno-functional characteristics of the powder. Here, the effect of the spray drying conditions on the yield and selected nutritional components of the milk powder was studied using a bench top spray dryer. However, there is need to translate these findings to an industrial volume dryer. These findings will play a big role in future spray drying operations since retention of important nutritional components is an important part of food processing.

Inline acoustic monitoring to determine fluidized bed performance during pharmaceutical coating

Fluidized beds are used by pharmaceutical manufacturers for multi-particulate drug coating. They provide effective mass and heat transfer; however, unit optimization can be difficult due to the multivariate nature of a fluidized bed system. This research explores the use of passive acoustic emissions monitoring as a method to improve temperature management during pellet coating. A piezoelectric microphone was placed inside the exhaust of a conical top spray fluidized bed. Spherical 1000 μm pellets were coated while recording acoustic emissions. Fluidization air temperature was adjusted between trials as a controlled variable to determine if pellet drying rate could be extracted from the data. During each trial, pellets became damp as the coating solution was applied. Drying stages were used to remove moisture whereby pellet fluidization continued without spraying. The moving standard deviation of the acoustic emissions increased by approximately 40 mV during each 2-min coating stage. The emissions then decreased during drying. This decrease was at a rate proportional to pellet drying independently measured at each controlled temperature. The overall coating-drying emissions profile was similar for trials using either sugar or Acryl-EZE® coating solutions. Passive acoustic emissions monitoring is non-invasive and provides reliable coating and drying information during fluidized bed operation.