Inspección de los elementos del sistema

Some spray drying experiments resulted in reduced product yields due to product depositions on the spray nozzle (Figure 7). The deposits occurred either extensively on the whole spray nozzle or were limited to the surroundings of the spray mesh. In both cases, the deposited powder was lost and the overall yield diminished. In addition, in some instances, the deposited powder became a heavy crust and burst off as product lumps contaminating the fine powder in the electrostatic particle collector.

Factors influencing the crust formation could be especially the used solvent, the spray-dried substance and the applied process parameters (Table 3). Among the factors related to the vibrating mesh spray technology, the drying air flow profile inside the spray dryer might be of significance. Although the drying air is laminar through the drying chamber, the spray nozzle works like a barrier in the gas flow and leads to the formation of local gas currents, which tend to entrain the spray 15. As a consequence, generated droplets flow back and deposit on the nozzle surface. Another reason for product deposits might be the electrostatic attraction of aerosol droplets towards the metallic surfaces of the spray nozzle. This effect might be further aggravated by temperature differences between the aerosol and the metallic nozzle surfaces. As user a certain influence on the outcome of a specific spray drying experiment can be exerted by changing process conditions, as well as substance and solvent related factors.

Table 3 Possible influences on crust formation tendency during spray drying processes

Technology related Process related Substance related Solvent related ƒ Flow profile / entrainment

ƒ Electrostatic effects ƒ Temperature differences ƒ Spray pulse

ƒ Inlet temperature ƒ Mesh size ƒ Air flow rate

ƒ Solubility ƒ Hygroscopicity ƒ Stickiness ƒ Surface tension ƒ Viscosity ƒ Conductivity ƒ Permittivity ƒ Boiling point Figure 7 Crust formations on the nozzle of the Nano Spray Dryer B-90

When working with traditional spray dryers, yield and success of a spray drying experiment are influenced by optimizing drying air inlet temperature, nozzle gas flow rate, liquid feed flow rate, and aspirator capacity. Traditional spray dryers offer a larger setting of the drying air inlet temperature (typically up to 220 °C). The nozzle gas flow rate exerts a direct influence on the particle size due to an increase in kinetic energy for the liquid atomization 9. The drying air inlet temperature in the Nano Spray Dryer B-90 can be adjusted between 60 - 120 °C. The high thermal efficiency of the process allows drying without damage of the product. Moreover, the smaller droplets evaporate quickly and require a lower drying temperature. The aperture size of the applied vibrating mesh is the critical parameter for particle size adjustment, which is equivalent to the spray gas flow in traditional pressurized air nozzles. The spray solution throughput in the Nano Spray Dryer B-90 is mainly determined by the aperture size of the applied mesh. In contrast, the liquid feed rate in traditional spray dryers is adjusted by the pump speed to obtain a certain outlet temperature and particle size 16, 17. The outlet gas temperature in the Nano Spray Dryer B-90 is controlled by the drying air flow rate (80 - 120 L/min) and the spray intensity (0 - 100%). The electrostatic particle collector works at fixed conditions and can not be influenced by the spray dryer operator directly. The system controls optimal particle separation conditions.

It is clearly recognized that the nozzle deposition is affected by the physicochemical nature of the spray-dried substance. Its maximal possible solute concentration limits the maximal achievable particle size and throughput. The substance hygroscopicity is inter alia responsible for the residual moisture content of the spray-dried powder. Some substances, like trehalose, have a highly sticky nature compared to noncohesive substances like salts 17. This might also lead to an increased sticking behavior of droplets to the nozzle. In addition, solvent physicochemical parameters, like surface tension, viscosity and conductivity, are considered to impact the crust formation. Some investigations regarding the influence of surface tension and viscosity on aerosol properties have been conducted 11. However, the processes during spray drying are more complex than during spraying into room air and the possibility remains that the additional drying factors provoke crustification of spray solutions.

Various spray drying experiments were conducted in order to analyze the effects of surface tension, viscosity and conductivity of spray solutions on nozzle deposition and yield reduction. Table 4 compares the experimental results in sets of two. Each set of experiments was performed under identical spray drying conditions (mesh size, inlet temperature, drying air flow rate). For example, set 1 comprises two experiments of griseofulvin with identical spray drying parameters (70 °C Tin / 5.5 µm mesh size), but different organic solvents. Griseofulvin dissolved in methanol / acetone (ratio 80:20) led to satisfying spray drying

results with no crustification, whereas dissolution in pure acetone formed a heavy crust on the spray nozzle and the final powder product was contaminated by crusty lumps. For the sets 2 - 5, the choice of either solute concentration or solvent clearly led to differences in process quality and crust formation.

Table 4 Sets of spray drying experiments for evaluation of crust formation Set No crustification Crustification

1 0.44% Griseofulvin in methanol / acetone 0.15% Griseofulvin in acetone 2 5% Salicylic acid in acetone 5% Salicylic acid in ethyl acetate 3 1% Benzocaine in ethanol 1% Benzocaine in acetone 4 1% Salicylic acid in ethyl acetate 5% Salicylic acid in ethyl acetate 5 0.44% Griseofulvin in methanol / acetone 0.5% Griseofulvin in ethyl acetate

Figure 8 depicts the viscosity, surface tension and conductivity values of the respective spray solutions. No significant correlation between spray solution properties and crustification tendency could be established, neither for the experiments without crustification (circles), nor for the ones with crustification (squares). These findings indicate that virtually any substance can be spray dried successfully, as long as the right experimental setup (solvent, concentration, etc.) is used.