Atomization Pressure Research Articles

Physical isolation strategy in multi-layer self-nanoemulsifying pellets: Improving dissolution and drug loading efficiency of ramipril.

Liquid self-nanoemulsifying drug delivery systems (SNEDDS) face challenges related to stability, handling, and storage. In particular, lipophilic and unstable drugs, such as ramipril (RMP) and thymoquinone (THQ), face challenges in oral administration due to poor aqueous solubility and chemical instability. This study aimed to develop and optimize multi-layer self-nanoemulsifying pellets (ML-SNEP) to enhance the stability and dissolution of ramipril (RMP) and thymoquinone (THQ). Liquid SNEDDS containing RMP and black seed oil (as a natural source of THQ) were prepared and characterized. The fluid-bed coating process was optimized by evaluating critical parameters such as inlet temperature, product temperature, air flow rate, atomizing air pressure, spray rate, and column height. Single-layer (SL-SNEP) and multi-layer (ML-SNEP) self-nanoemulsifying pellets were developed by applying various functional layers onto nonpareil sugar spheres. The pellets were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and in vitro dissolution studies. Optimized fluid-bed coating parameters resulted in high coating recovery (>80%) and excellent mono-pellet percentages (≥97%). SEM analysis revealed well-defined, completely solidified layers in ML-SNEP. DSC and XRD studies suggested RMP amorphization. In vitro dissolution studies showed >86% RMP and THQ release within 60 minutes for both SL-SNEP and ML-SNEP. The physical isolation strategy significantly improved drug loading efficiency, with ML-SNEP showing 109% RMP loading efficiency compared to 55% in SL-SNEP. The addition of moisture sealing and anti-adherent layers had no negative impact on drug release, with SNEP-5L (including the anti-adherent layer) showing higher dissolution efficiency for both RMP and THQ. This study successfully developed and optimized ML-SNEP as a novel approach for enhancing the stability and release of RMP and THQ. The physical isolation strategy was a key approach in enhancing drug loading efficiency while preserving the advantageous dissolution properties of liquid SNEDDS. This approach offers valuable insights for developing advanced oral drug delivery systems for poorly water-soluble and labile drugs.

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.

Effects of spray drying on the content of crystal proteins of Bacillus thuringiensis and the protection by organic and inorganic auxiliaries.

Spray drying is an important industrial method for the preparation of B. thuringiensis powder from fermentation liquor. The effect of spray drying on the crystal proteins, however, has not been reported in the literature so far. The present study systematically investigated the effect of inlet air temperature, outlet air temperature, atomizing air pressure and additives (including organic and inorganic auxiliaries) on the thermal destruction of crystal proteins of B. thuringiensis. The results indicated that the content of crystal proteins of B. thuringiensis powder decreased with increased inlet air temperature, outlet air temperature and atomising air pressure. The pseudo-z values for inlet air temperature, outlet air temperature and atomizing air pressure were 826.4℃, 204.0℃ and 4.74MPa, respectively. Among them, the outlet air temperature was a major parameter influencing the thermal destruction of crystal proteins, therefore, the decrease of the outlet air temperature was beneficial to increase the protein content in powder. Although the spray drying had an adverse effect on crystal proteins, the crystal protein content in spray-dried powder approached that in freeze-dried powder when the inlet air temperature of 165℃, outlet air temperature of 70℃ and atomizing air pressure of 0.15MPa were employed. The addition of some organic and inorganic auxiliaries to fermentation liquor can protect the crystal proteins from heat damage.

Spray system characterization for evaluating particle size enlargement in fluidized bed agglomeration

Droplet size is a crucial success factor for increased particle size in the agglomeration process. Thus, this work aimed to analyze the physicochemical properties of maltodextrin solutions used as the binder, their influence on the size of the formed droplets, and their relationship to particle growth. The primary CMC particles had an average size of 295.5 ± 10.0 µm, and at the end of the process, the agglomerates reached chord lengths ranging from 336.5 ± 10.6 µm to 378.3 ± 8.6 µm. Three maltodextrin solutions (5.0%, 20.0%, and 35.0% w/w) were characterized for that in terms of physicochemical properties and droplet size, and following that, the binder concentrations, binder flow rate, and atomizing air pressure were evaluated. The binder liquid concentration is the most outstanding parameter for the agglomeration process regarding particle growth under experimental conditions.

REVIEW: PROCESS OF FLUID BED GRANULATOR PARAMETERS AT THE TIME OF SCALE UP IN GRANUL PRODUCTION

Scaling up is one of the difficulties faced by the production process of the pharmaceutical industry. We must manufacture in higher quantities than a laboratory size with set requirements as we scale up. Understanding the crucial variables that affect the final product's specifications will aid in choosing appropriate upgrade settings. Fluidized-bed granulation is one of the most frequently used techniques to increase the scale of the pharmaceutical industry. The complex fluidized bed granulation process is influenced by several factors. The most important process variables were the intake air temperature and humidity, concentration of the binder solution, spray rate, atomizing air pressure, and air flow rate. Numerous investigations have examined the effects of large-scale fluid bed granulation. An improved fluid bed granulation technology was employed based on the relative droplet size and moisture content of the powder in the bed after the spraying cycle. These values are comparable, demonstrating that the granulation procedure can be enhanced by considering only the moisture content of the powder and relative droplet size. Keywords: fluid bed granulation, process parameters, scale up

Fluidized spray driven polymer mediated ultra stable Aluminum metal coating with enhanced dielectric properties

In this work, a novel method for coating the polymeric substrate with an aqueous metallic powder (Aluminum) solution was developed. In the modified fluidized bed, assisted bottom spray coater was used to achieve the strong interfacial coating of the aluminum on the fluidized spherical expanded polystyrene (EPS) substrate and polyvinyl alcohol (PVA) as a binder. The coated aluminum metal exhibits a layered thickness of 340 ± 50 µm. The effect of fluidization airflow rate, spray rate, atomization air pressure, and inlet air temperature on the aluminum coating on the EPS spheres was investigated for the first time. The substantial integrity, interfacial bonding and surface morphology of aluminum coating were confirmed through XRD, FTIR, shaking test and SEM analysis. In addition, a remarkably high dielectric constant of 12,000 compared to the dielectric constant of the pristine EPS sphere of 60 at low frequency was observed.

Optimization of Fluidized-Bed Process Parameters for Coating Uniformity and Nutrient-Release Characteristics of Controlled-Release Urea Produced by Modified Lignocellulosic Coating Material

Controlled-release fertilizers are employed in precision agriculture to optimize technology-enabled farming without environmental deterioration. In this study, almond-shell lignocellulosic waste particles are chemically processed to synthesize a coating suspension for the production of controlled-release urea (CRU) in a Wurster fluidized-bed reactor. The interactive effect of process parameters such as atomizing air pressure (Pair), fluidized-bed temperature (Tfb), spray rate (Rspray), and fluidizing-air flow rate (Qair) on the (i) coating-film uniformity of CRU particles and (ii) longevity of nutrient-release from CRU is reported. CCRD is used with RSM to design the experiments for the optimization of nutrient-release performance and coating-film uniformity in terms of a coefficient-of-variance (CoV) of film thickness. The regression models indicate a good prediction of coating-film uniformity and nutrient-release time, with R2 = 0.971 and R2 = 0.98, respectively. The optimum conditions for coating-film uniformity are determined to be Pair = 3.5 bar, Tfb = 80 °C, Rspray = 0.15 mL/s, and Qair = 72 m3/h, with a predicted CoV film thickness of 11.5%. Similarly, Pair = 3.2 bar, Tfb = 78 °C, Rspray = 0.125 mL/s, and Qair = 75 m3/h are the optimum conditions for nutrient-release performance, with a prediction nutrient-release time = 56 h. The experimental validation yields a CoV of film thickness = 12.6% and a nutrient-release time = 49.5 h, indicating good agreement between predicted and experimental values. In addition, Tfb appears to be the most significant parameter.

Profiling the process development of Wurster coating for modified release capsule products in approved drug product applications

In this paper, we have studied Wurster Coating operation for the manufacture of modified release (MR) capsule products submitted to FDA as New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) by using a data-driven approach. We have collected and classified information into Wurster coating associated process variables, quality attributes, and scale up strategies under Quality by Design (QbD) paradigm. We have quantified the importance and risk of the process variables and quality attributes by analyzing reported frequencies and risk factors, respectively. We have also included analysis of quality attributes listed with high risk factors, such as weight gain, particle size, assay, dissolution of coated beads, and water content/ Loss on drying (LOD) and the process variables with higher risk factors, such as product temperature, spray rate, atomization air pressure, Inlet air volume and Inlet air temperature, etc.We believe that the knowledge obtained through profiling Wurster coating operation will help the industry to further improve the quality of drug product applications regarding the development of this unit operation. We hope systematic profiling of pharmaceutical unit operations under QbD paradigm can provide support for FDA’s IT initiatives aiming at improving the efficiency and consistency of FDA’s quality assessment.

Gap optimization of electrostatic aerial spray nozzles for low-speed aircraft

The gap between the spray plume and the cylindrical charging electrode for an aerial electrostatic spray nozzle is critical to achieve maximum chargeability of spray formulations prior to aerial applications of pest control products. Seven discrete gaps from the nozzle tip to the trailing edge of the electrode were tested for spray chargeability. A spray mixture of tap water and a non-ionic surfactant with an electrical conductivity of 1012.75 ± 6.70 μS was atomized through three different-sized nozzle tips (TXVK-3, TXVK-4, and TXVK-6) in a controlled high-speed wind tunnel operated at 6 different airspeeds between 80 and 177 km/h with two atomizing air pressures, 310 and 517 kPa, representing minimum and maximum values commonly used in rotary wing agricultural aircraft. The TXVK-3 nozzle yielded significantly higher charge-to-mass ratio (Q/M > 1.0 mC kg-1) compared to the TXVK-4 and TXVK-6 nozzles. At 310 kPa liquid pressure, the 6.5- and 9.3-mm gaps produced significantly higher spray charge. Data indicated that the chargeability of aerial electrostatic sprays can be improved using a smaller orifice and lower flow rate nozzle operated at a lower liquid pressure and higher airspeed. Results from this study may help aerial applicators better understand the optimum operational parameters required to maximize the electrostatic charge of spray formulations while flying low speed aircraft.

Investigating parameters that influence tablet logo bridging

The effect of a number of pan coating process parameters on the incidence of tablet logo bridging were investigated in this study. Parameters investigated included spray rate, pan speed, process air temperature, atomization and pattern air pressure. The results of the study demonstrated that logo bridging defects were significantly affected by the relationship between atomising and pattern air pressures, spray rate and process air temperature. The study also examined the shape and pattern of the spray at different conditions and found a link between the spray pattern and the incidence of logo bridging.

Protective coating of highly porous alginate aerogel particles in a Wurster fluidized bed

Alginate aerogel particles were successfully coated with a copovidone and hydroxypropyl cellulose based polymer in a Wurster fluidized bed. The results indicate that the pores of aerogels were not damaged during the process. Several sets of experiments were conducted at three different temperatures and atomizing air pressures. Coating time for all the runs ranged from 5 min to 40 min and the coating thickness ranged from 12.4 ± 4.6 μm to 170.6 ± 43.3 μm.Changing bed temperature led to significant changes in coating thickness whereas both bed temperature and atomizing pressure affected coating layer surface morphology. The smoothest coating layer surface and the highest coating efficiency which was 69.2 ± 0.4% were achieved at 50 °C with 1.7 bar atomizing pressure. At this condition, the coating layer thickness increased linearly with coating time.

DEVELOPMENT, OPTIMIZATION AND EVALUATION OF PULSATILE DRUG DELIVERY CAPSULES LOADED WITH CARVEDILOL BY APPLYING QUALITY BY DESIGN

Objective: The purpose of this research is to find the best way for designing carvedilol pulsatile drug delivery system capsules. Methods: The research paves the way to improve the method of preparing carvedilol pulsatile drug delivery by adjusting critical material attributes (CMA) such as coating polymer concentration, critical process parameters (CPP) such as inlet temperature and atomizing air pressure, and their impact on critical quality attributes (CQA) like particle size (PS in nm), entrapment efficiency in percentage (% EE) and amount of drug delivered in percent (%ADR) at 12 h in the carvedilol pulsatile pellets filled capsules by applying the Box-Behnken design. By varying the polymer concentration and process parameters, nearly 15 formulations were created. Results: Based on the influence of CMA, CPP on CQA, the formulation CP13 was determined to be the most optimized formulation among the 15 formulations. The optimized levels of CMA were found to be-1 level of coating polymer concentration and CPP was found to be-1 level of inlet temperature, 0 level of atomizing air pressure and it optimized CQA like PS was found to be 1017.5±8.4 nm, % EE was found to be 96.8±2.8 %, % ADR at 12 h was found to be 88.4±3.4 %. Carvedilol Pulsatile drug delivery system was designed by using optimized fluidized bed coater in order to decrease the usage of attributes, decrease the productivity cost and enhance the usage of specific attributes at fixed concentration for further manufacturing scale. Conclusion: By the current results it was concluded that the optimized CMA and CPP that shown in the results are the suitable attributes for the best formulation of carvedilol pulsatile drug delivery system capsules.

Hot Melt Coating: Development and Optimization of Controlled Release Formulation and Process of Oxcarbazepine

Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system for anti-epileptic drug Oxcarbazepine. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of solid lipid material and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus on HMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization (by CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Experimental evaluation of parameters affecting the coating performance of urea seeds in a prototype bottom external mixing spray two-fluid nozzle fluidized bed granulator

A comparative study was carried out on coating and coalescence mechanisms of urea seeds by molten urea, using external mixing two-fluid nozzle fluidized bed granulator (FBG). In this regard, the variables influencing a new parameter defined as coating performance (CP) of urea granules were modeled. The variables included of spraying and atomizing air pressures, masses of loaded seeds and molten urea, and mass flow rate of fluidization air. Considering all interactions between the variables, the optimum conditions for obtaining the maximum 60% CP was determined. Furthermore, according to cumulative size distributions analyses, the conditions leading to proper size guide number (SGN) and uniformity index (UI) was characterized. The SEM observations showed that, in most cases, the porous initial urea seeds were coated by a compact molten urea layer. Considering the dimensionless Stokes numbers, the extent of fluidized particles’ velocity leading to domination of coating or coalescence was verified.

Development and Optimization of Controlled Release Formulation and Process of Levetiracetam with Hot Melt Coating Technology

Conventional coating processes are based on aqueous or organic solvent system, resulting in the lengthy and tedious processes where use and removal of solvents consumes lots of energy and resources. Also, solvent disposal is a critical issue considering environmental hazard.Hot melt coating process avoids use of solvent and is short and energy-efficient process. Here, Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system to deliver highly water soluble Biopharmaceutical Classification System (BCS) class-I drug Levetiracetam. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of lipid and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus onHMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment Failure Mode and Effect analysis (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization by Central Composite Design (CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Characteristics of Flame Stability and Gaseous Emission of Bio-Crude Oil from Coffee Ground in a Pilot-Scale Spray Burner

Coffee ground has been recently considered as a new biomass resource in relation to the increasing coffee consumption worldwide. The bio-crude oil can be produced by fast pyrolysis of coffee ground, and it has advantages of larger heating values in comparison with those from other biomass. But the bio-crude oil from coffee ground has a significantly high viscosity which can hinder the application to conventional burners. In this study, a pilot-scale burner system with a 35 kW capacity with an air-blast atomizing nozzle was developed for the combustion of bio-crude oil from coffee ground with a high viscosity. A downward fuel injection system was adopted to enhance the ignition of fuel spray and the flame stabilization, and a movable block swirl generator was installed for the combustion air. The bio-crude oil was blended with ethanol at the volumetric ratio of 9:1 to enhance the combustion characteristics. The effect of various atomizing air pressures, swirl intensities, and overall equivalence ratios on the flame stability and gaseous emission were investigated to find out the optimum operating conditions for a bio-crude oil burner.

Ultra-low emission combustion of diesel-coconut biodiesel fuels by a mixture temperature-controlled combustion mode

Liquid fuels are likely to remain the main energy source in long-range transportation and aviation for several decades. To reduce our dependence on fossil fuels, liquid biofuels can be blended to fossil fuels – or used purely. In this paper, coconut methyl ester, standard diesel fuel (EN590:2017), and their blends were investigated in 25 V/V% steps. A novel turbulent combustion chamber was developed to facilitate combustion in a large volume that leads to ultra-low emissions. The combustion power of the swirl burner was 13.3 kW, and the air-to-fuel equivalence ratio was 1.25. Two parameters, combustion air preheating temperature and atomizing air pressure were adjusted in the range of 150–350 °C and 0.3–0.9 bar, respectively. Both straight and lifted flames were observed. The closed, atmospheric combustion chamber resulted in CO emission below 10 ppm in the majority of the cases. NO emission varied between 60 and 183 ppm at straight flame cases and decreased below 20 ppm when the flame was lifted since the combustion occurred in a large volume. This operation mode fulfills the 2015/2193/EU directive for gas combustion by 25%, which is twice as strict as liquid fuel combustion regulations. The 90% NO emission reduction was also concluded when compared to a lean premixed prevaporized burner under similar conditions. This favorable operation mode was named as Mixture Temperature-Controlled (MTC) Combustion. The chemiluminescent emission of lifted flames was also low, however, the OH* emission of straight flames was clearly observable and followed the trends of NO emission. The MTC mode may lead to significantly decreased pollutant emission of steady-operating devices like boilers, furnaces, and both aviation and industrial gas turbines, meaning an outstanding contribution to more environmentally friendly technologies.

In-line particle size measurement and process influences on rotary fluidized bed agglomeration

In-line particle size measurement with a spatial filter velocimetry probe for process control was already carried out successfully in conventional fluidized bed coating and agglomeration but has not yet been investigated in rotary fluidized bed agglomeration with a tangential spray for granulate and pellet manufacturing. In this project, a batch laboratory fluidized bed apparatus with a rotor insert and a tangential spray nozzle was used to investigate the feasibility of in-line particle size measurement with a spatial filter velocimetry probe and to detect critical process parameters.First, particle size and particle size distribution of a placebo mixture including small and large pellets were measured directly with the in-line probe in the rotary fluidized bed without spraying and without agglomeration. The volume density distribution shows bimodal curves, the peaks of which are related to the different ratio of pellets. Second, microcrystalline cellulose powder was agglomerated with a binder solution in the rotary fluidized bed by tangential spraying. At-line dynamic image analysis for the particle size measurement was used for comparison and showed similar results to the spatial filter velocimetry method. A Plackett-Burman screening design identified spray rate, atomizing air pressure, rotor disk velocity and batch size as critical process parameters by measuring particle size, particle size distribution and sphericity. The spatial filter velocimetry probe can be used in rotary fluidized bed agglomeration with tangential spray for process control.

Design and construction of the pressure swirl nozzle and experimental investigation of spray characteristics

This paper focuses on the structure and performance of the pressure swirl nozzle and the study of liquid atomization. In this study, the atomizer has been designed and some experiments have been performed on it. Since image processing is an efficient method for measuring the size of the droplet and since it considerably reduces the total measuring time and eliminates the subjective observer’s error in sizing and counting spray drops, a digital camera has been used for capturing images and image processing has been done by the MATLAB software. The results show that by increasing the atomization air pressure, the spray angle increases and the droplet’s size decreases. It is concluded that the spray angle is a function of the atomization air pressure and orifice diameter. Moreover, when the distance from the spray centre line increases, the droplet’s average velocity decreases.

Optimization of spray drying process parameters for production of groundnut milk powder

In India, groundnut is mainly used for oil extraction or consumed in roasted form prompting a need for diversification to further increase its value and utility. In the present study, spray drying of groundnut milk was carried out using three variables of spray dryer i.e., inlet air temperature (180–220 °C), atomization air pressure (2–3 bar), feed pump speed (24–36 rpm) using Box-Behnken design of Response Surface methodology. The moisture content of powder decreased with an increase in inlet air temperature and atomization air pressure. The bulk density increased with increase in atomization air pressure. Maximum dispersibility (98.48%) was observed at an atomization air pressure of 2.57 bar. The insolubility index of the powder increased and lightness value (L*) decreased with an increase in inlet air temperature. The optimized conditions for spray drying of groundnut milk were inlet air temperature: 186 °C, atomizing air pressure: 2.5 bar and feed pump speed: 27 rpm.