A Focus on Spray Dryer Technique

INTRODUCTION

Salbutamol sulphate is an inhaled drug used in the management of asthma and Chronic Obstructive Pulmonary Disease (Akinbami L. J. et al, 2016). It is an important bronchodilator that has been aerosolized for efficiency as a beta-2 adrenergic agonist (Lin J. T. et al, 2017). The spray dryer technique has been researched and further research is still undergoing on it as it is applied in many fields such as the food industry in milk powder production and most importantly in the medical field in pharmaceutical preparation of inhalers (Chen Z. H. et al, 2018). It has enhanced pulmonary drug delivery in the management of respiratory tract diseases, making it a crucial topic for those seeking healthcare dissertation help. Breakthroughs have also been seen in vaccines e.g. measles vaccine and insulin that can be inhaled. Respiratory drugs generated with this technique have localized drug deliveries specifically to the lower respiratory tract through either pressurized meter dose inhalers (Pmdi) such as salbutamol inhalers and dry powder inhalation for (DPI) COPD and emphysema (Jones B. P. et al, 2018).

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Respiratory drugs generated using the spray dryer technique must have specific aerodynamic properties to enable them to efficiently reach the lower respiratory tract for respiratory diseases treatment and management (Chen Y. Z. 2016). These drugs require a size range of 2.5 – 6 micrometers to be able to reach the lower respiratory tract and its extremities. The spray drier has been specifically developed for this purpose and when its parameters and requirements have been fully met, potent and effective drugs are produced (Wang X. F. et al, 2019).

This experiment aims to examine the efficiency of the BUCHI – 190 Spray Dryer and characterized the particle size of the salbutamol sulphate particles generated to fully comprehend the Laser Diffraction Analysis.

AIM

To prepare salbutamol sulphate particles for inhalation using the spray design technique.

To characterize salbutamol sulphate particle size with Laser Diffraction Analysis.

EXPERIMENT DESIGN

One aim of the experiment was to prepare dry salbutamol sulphate particles for dry powder inhalation for the treatment of Chronic Obstructive Pulmonary Disease. 50 ml of salbutamol sulphate solution was used of 5% and 10% aqueous solutions. 2 bars and 1 bar atomization rates were used.

MATERIALS

50ml of 5% and 10% aqueous salbutamol sulphate solution.

PROCEDURE

PROCEDURE

Results analysis of batch 1 salbutamol sulphate large particles from low atomization rate

Results analysis of batch 1 salbutamol sulphate large particles from low atomization rate Results analysis of batch 1 salbutamol sulphate large particles from low atomization rate

Averagely 16.2% of the sample produced the ideal particle size between 2.5 – 6 micrmeters, 32% had particles of sizes below 2.5 micrometers 51% had particles larger than 6 micrometers. Most of the particles are large due to the low atomization rate that results in less dispersion of the droplets and they may end up merging as they are dried resulting in large particles.

Results from analysis of batch 2 salbutamol sulphate particles from a high atomization rate

Results from analysis of batch 2 salbutamol sulphate

Averagely 16.2% of the sample produced the ideal particle size between 2.5 – 6 micrometers, 32% had particles of sizes below 2.5 micrometers 51% had particles larger than 6 micrometers. High atomization rate disperses the droplets more and they are dried faster resulting in smaller particles.

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DISCUSSION

The BUCHI - 190 Spray Dryer is designed with an automised microprocessor at the drying chamber which tightly regulates the inlet temprature despite fluctuations in the air flow rate. It also ensures there is a low maximum inlet temprature in the drying chamber for heat sensitive samples, especially biological samples. The cyclone separator has a secondary filter downstream to ensure only the finely atomised particles go to the product collection chamber. This increases the quality of its produts.

BUCHI – 190 spray drier is designed based on principles that ensure its efficiency in its functions (Mazzoni L. et al, 2016).

Drying air characteristics.

Atmospheric air is filtered and heated to specified temprature to be able to evaporate the water in the sample.

Atmospheric air is filtered and heated

Atomization is important in making the droplets spherical and increasing the surface area of the droplet, speeding up evaporation of the water. It also reduces the surface tension of the sample for easier evaporation. Before atomization several techniques are also applied to reduce surface tension (Templeton A. G. et al, 2017).

Drying

In the drying chamber, the sample is atomized and moves at an average speed of 100 – 200m/s. The small droplets that went through a noozle is heated with air flowed in through either co-current flow, counter-current flow or mixed co-current and counter-current flow to dry the droplets before they touch the walls of the container to avoid deposition (Hong J. G. 2017). The evaporated water from the sample also joins the drying air and contributes to the drying of the sample further (Agrawl D. K. et al, 2018).

The resulting particle size depends on the mean droplet size. The spray dryer either has the single stage drying or the two stage drying technique, the latter being more efficient (Ameredes B. T. et al 2016). The feed concentration is crucial in the type of particle size desired. Increased concentration of the feed means there is a decrease in the water evaporated and more solid particles will be formed (Chorley B. N. et al, 2017). Subsequently, there is less water on evaporation of the sample hence a decrease in the partial pressure in the chamber resulting in particle sizes difficult to separate in the cyclone compared to lower feed concentration (Cho S. H. et al, 2018).

Particle collection

The particles accumulate depending on their finness and are subsequently redirected to different chambers. The first collection is that of dense particles while the second collection is of the fine particles from the humid air (Nigo Y. I. et al, 2016).

In the cyclone separator, centrifugal force is used. A stream of air moves in the cyclone downwards in the outer vortex in high velocity and the centrifugal force separates the particles according to size. The fine particles accumulate at the cone of the cyclone and the gas is expelled (Walle U. K. et al, 2017). The secondary filter ensures only fine particles are collected at the product collection chamber.

Laser diffraction analysis or laser diffraction spectroscopy is a technique essential in determining the actual aerodynamic size of the particles generated by the spray dryer (Tucker G. T. 2017). The principle is to use the diffraction of light beam after it passes through the particle to determine its geometric dimentions. The Fraunhofer diffraction theory is applied where the intensity of the laser light scatttered by the particle is directly propotional to its size (Dennis J. et al, 2017).

He – Ne laser is used and the machine is connected to a high voltage power supply. The laser is passed through the particles and the diffracted light first passes through a lens before it is directed to a sensor which calibrates the frequency and the wavelength of the beam and uses it to calibrate the size of the particle (Krebs S. E et al, 2016). The large drug particles tend to diffract light with small angles compared to the small particles that diffract light with large angles. This corresponds to the Mie theory of light scatter (Gradon L. R. et al 2018).

The advantage of this technique is the wide dynamic range of particle measurement from submicrons to millimeter measurement. It also calibrates the values faster than other techniques. It also shows if the particle is of optimal particle morphology and is stable for pulmonary delivery (DeNicola et al, 2016).

Particle size reduction and the narrow size range allowed in pulmonary drugs is essential to successfully treat or manage the underlying condition (Yan C. X. et al, 2018). Sizes below 2.5 micrometers will undergo systemic absorption and will result in adverse side effects in the body. Those more than 6 micrometers will not be able to reach the lower respiratory tract and the symptoms of the disease will worsen and the particles may lead to further obstruction in the airway (Asmus M. J. et al, 2016).

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CONCLUSION

Particles of salbutamol sulphate solution were successfully produced by spray drying and the particles sizes were effectively characterized using the laser diffration analysis.

REFERENCE

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Ameredes B.T., Calhoun W.J. 2016. Modulation of GM-CSF release by enantiomers of β-agonists in human airway smooth muscle. J Allergy Clinic Immunology.

Asmus M.J., Hendeles L. 2016. Levalbuterol nebulizer solution: is it worth five times the cost of albuterol? Pharmacotherapy.

Chen Y.Z. 2016. Prevention and treatment of childhood asthma in China. World J Pediatrics.

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