Mechanism of droplet-formation in a supersonic microfluidic spray device

Spray drying is an approach employed in automotive, food, and pharmaceutical industries as a robust and cost efficient liquid atomization technique offering direct control over droplet dimensions. The majority of commercially available spray nozzles are designed for large throughput spray drying applications or uniform surface coating, but microfluidic nebulizers have recently been developed as small scale alternatives. Here, we explore the physical parameters that define the droplet size and formation under supersonic flow conditions commonly found in microfluidic spray drying systems. We examined the spray nozzle operation using high speed imaging and laser scattering measurements, which allowed us to describe the spray regimes and droplet size distributions. It was determined that by using this spray nozzle device, droplets with diameters of 4–8 μm could be generated. Moreover, we show that the supersonic de Laval nozzle model can be used to predict the average droplet size. Our approach can be used as a platform for interfacing fluid microprocessing with gas phase detection and characterization

Single droplet experimentation on spray drying:evaporation of sessile droplets deposited on a flat surface

Abstract: Individually dispensed droplets were dried on a flat surface to mimic the drying of single droplets during spray drying. A robust dispensing process is presented that generates small droplets (dp>150 µm). A predictive model based on Bernoulli’s law accurately describes droplet size with varying liquids and dispensing parameters. Shrinkage of the droplets, monitored with a camera, was described using mass balance equations. Finally, a Sherwood correlation was derived to describe the mass transfer coefficient for sessile droplets. This work forms the basis for the development of a platform for high throughput experimentation on spray drying

Encapsulation of citrus by-product extracts by spray-drying and freeze-drying using combinations of maltodextrin with soybean protein and ι-carrageenan

The effect of different combinations of maltodextrin (MD) coating agents (MD, MD + soybean protein, and MD + ι-carrageenan) on the encapsulation of lemon by-product aqueous extracts using freeze-drying and spray-drying were investigated. The total phenolic content (TPC), total flavonoid content (TFC), and ferric ion reducing antioxidant power (FRAP) of the microparticles were evaluated. Freeze-drying with the mixture of MD + soybean protein resulted in the highest retention of TPC, TFC, and FRAP (1.66 ± 0.02 mg GAE/g d.b., 0.43 ± 0.02 mg CE/g d.b., and 3.70 ± 0.05 mM TE/g, respectively). Freeze-drying resulted in microparticles with lower moisture content (MC) and water activity (aw) than those produced by spray-drying. Specifically, the MC and aw of the microparticles produced by freeze-drying ranged from 1.15 to 2.15% and 0.13 to 0.14, respectively, while the MC and aw of the microparticles produced by spray-drying ranged from 6.06% to 6.60% and 0.33 to 0.40, respectively. Scanning electron microscopy revealed that spray-drying resulted in the formation of spherical particles of different sizes regardless of the type of coating agent. Although freeze-drying resulted in microparticles with amorphous glassy shapes, the mixture of MD + soybean protein resulted in the formation of spherical porous particles. X-ray diffraction revealed a low degree of crystallinity for the samples produced by both techniques.</p

Investigation of a novel 3-fluid nozzle spray drying technology for the engineering of multifunctional layered microparticles.

OBJECTIVE: To examine the potential of a novel 3-fluid nozzle spray drying technology to formulate differentiated layered microparticles (MPs) of diclofenac sodium (DFS)/ethyl cellulose (EC). METHODS: DFS/EC MPs were formulated using the inner and/or outer nozzles of a novel 3-fluid nozzle and compared with MPs formed using conventional (2-fluid) spray drying. MPs were characterised for particle size and for morphology by TEM and SEM. Distribution of DFS and EC of MPs was analysed by FT-IR and DSC. A two-factor, three-level (3(2)) factorial design was applied to investigate the effect and interaction of total feed solid content (TSC) and feed flow rate (FFR) on MP size, D(50%) and D(90%), bulk density and MP yield. RESULTS: Interestingly, TEM demonstrated that MPs formed by 3-fluid nozzle spray drying showed a heterogeneous internal morphology consisting of a core and coat, characteristic of a microcapsule. In comparison, MPs from conventional spray drying showed a homogeneous internal morphology, characteristics of a matrix system. This differential distribution of DFS/EC was supported by FT-IR and DSC. Results of multiple linear regression analysis showed a linear relationship for the effect of TSC and FFR on all responses except for D(50%) where a quadratric model was valid. The effect of TSC/FFR on MP size and yield was similar to conventional spray drying. CONCLUSION: The novel 3-fluid nozzle spray drying offers a new method of designing layered microparticles or microcapsules which can have wide applications from drug stabilisation to controlled drug delivery and targeting

Simulation and control of spray drying using nozzle atomizer spray dryer

Spray drying is a commonly used method of drying a liquid feed through a hot gas. This study aims to obtain the empirical model of the spray drying process of full cream milk using a nozzle atomizer spray dryer, Lab-Plant SD 05 Laboratory Scale Spray Dryer. Inlet air temperature was chosen as the manipulated variable and outlet air temperature was the controlled variable. No disturbance was considered in this process. The model was obtained from empirical model development and it can be represented using first order plus time delay (FOPTD). The empirical dynamic model of the spray drying of full cream milk was simulated using SIMULINK to evaluate the performance and robustness. The PI and PID controllers were applied to implement the control strategies of the process. The effects of parameter uncertainties were investigated. From the observation, the direct synthesis tuning method has been found as a good controller tuning for both controllers in spray drying control system

Inhalable spray-dried chondroitin sulphate microparticles: effect of different solvents on particle properties and drug activity

Spray-drying stands as one of the most used techniques to produce inhalable microparticles, but several parameters from both the process and the used materials affect the properties of the resulting microparticles. In this work, we describe the production of drug-loaded chondroitin sulphate microparticles by spray-drying, testing the effect of using different solvents during the process. Full characterisation of the polymer and of the aerodynamic properties of the obtained microparticles are provided envisaging an application in inhalable tuberculosis therapy. The spray-dried microparticles successfully associated two first-line antitubercular drugs (isoniazid and rifabutin) with satisfactory production yield (up to 85%) and drug association efficiency (60%-95%). Ethanol and HCl were tested as co-solvents to aid the solubilisation of rifabutin and microparticles produced with the former generally revealed the best features, presenting a better ability to sustainably release rifabutin. Moreover, these presented aerodynamic properties compatible with deep lung deposition, with an aerodynamic diameter around 4 μm and fine particle fraction of approximately 44%. Finally, it was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation independently of the used solvent.UID/Multi/04326/2019; SFRH/BD/52426/2013; ED481B 2018/071info:eu-repo/semantics/publishedVersio

Spray drying as a reliable route to produce metastable carbamazepine form IV

Carbamazepine is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least five polymorphic forms. Metastable form IV was originally discovered from crystallisation with polymer additives however has not been observed from subsequent solvent only crystallisation efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic carbamazepine solution. Characterisation of the material was carried out using diffraction, SEM and DSC. In situ Raman spectroscopy was used to monitor the spray dried product during the spray drying process. This work demonstrates spray drying provides a robust method for the production of form IV carbamazepine and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallisation approaches to produce metastable crystalline forms

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions

This work explores the use of both spray drying and D-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging was also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5 µm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (- 3.8 versus 0.5 nC/g for untreated material and -7.5 versus 3.1 nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1 – 0.3 3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM

Resistant maltodextrin as a shell material for encapsulation of naringin: Production and physicochemical characterization

YesHerein the potential of a relatively new water soluble fiber, resistant maltodextrin (RMD) to encapsulate grapefruit polyphenol, naringin, using spray drying was evaluated. Full factorial Design Of Experiments (DOE) for spray drying with two levels of fiber–naringin ratio and spray dryer inlet temperature was executed. Resulting powders were characterized with respect to particle size and morphology, crystallinity, thermal properties, moisture sorption and naringin aqueous solubility increase. A 60–80% encapsulation was achieved. Thermal and moisture sorption behaviors of these dispersions were found to be dominated by RMD. By varying fiber–naringin ratio and spray drying temperatures, naringin was able to disperse in amorphous form in RMD matrix, which led to 20–55% increase in aqueous solubility. Solubility enhancement was found to correlate positively with increasing fiber: naringin ratio and spray drying temperature due to multiple factors discussed in this study. In conclusion, fiber–polyphenol bicomponent nutraceutical was successfully developed based on a well-established encapsulation technology i.e. spray-drying

Mechanisms of burst release from pH-responsive polymeric microparticles.

Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release