Spray Drying: A Promising Technique to Enhance Solubility

 

Shital S. Shinde*, Girishchandra R. Mandake, Manoj M. Nitalikar

Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon, Maharashtra India-415404

 

ABSTRACT:

Poor solubility and bioavailability of an existing or newly synthesized drug always pose challenge in the development of efficient pharmaceutical formulation. Numerous technologies can be used to improve the solubility and spray drying technology can be successfully useful for development of product from lab scale to commercial scale with a wide range of powder characteristics. Spray drying is an interesting manufacturing technique for the pharmaceutical industry since it uses a one-step process for formation and drying of powders. Using this technique the number of unit operations is reduced, improving production efficiency and reducing costs. Since spray drying is a technique which can be easily automated and equipped for in-line product analysis. Current review deals with the importance of spray drying technology in drug delivery, basically for solubility and bioavailability enhancement, instrumentation, advantages and the various applications of spray drying. Overall, spray drying has a bright future due to its versatility, efficiency and the driving force of poorly soluble drugs.

 

 

 

INTRODUCTION:^[1][2][3][4]

The development of spray drying equipment and techniques evolved over a period of several decades from the 1870s through the early 1900s¹. Spray drying is an excellent technique for the rapid removal of solvent from a system, yielding particles with various properties that can be specifically designed². Due to the large number of poorly water-soluble drugs present in today's market, methods for generating drug particles with enhanced solubility are of crucial importance.

 

Spray drying is a very widely applied technique used to dry aqueous or organic solutions, suspensions and emulsions in the food, chemical, electronics, pharmaceutical and biopharmaceutical industry. Within the food industry spray drying is used to prepare a wide range of products, e.g. baby and infant food, instant coffee, dried milk products, tomato paste³.

 

Spray Drying Process⁴:

Spray drying involves the spraying of a liquid feed formulation (solutions, suspensions, emulsions) into a hot drying medium (air, nitrogen). The droplets formed by the atomization process are dried through solvent evaporation to form particles which are collected as a dry powder (Fig. 1). The drying of the spray continues until the desired moisture content in the dried particles is achieved, and the product is recovered from the air. It is a unique drying process since it involves both particle formation and drying. Process parameters such as inlet and outlet temperature of the drying medium and the atomization pressure influence the physico-chemical properties of the produced powders. The characteristics of the spray dried powder can be controlled, and the powder properties can be maintained constant throughout the continuous operation. With the different designs of spray dryers available, it is possible to select a dryer layout to produce either fine or coarse particle powders, agglomerates or granulates. The different spray drying systems are open cycle, closed cycle and semi-closed cycle.

 

 

Fig 1: Spray drying process

 

Spray drying process mainly involves five steps:

(i)     Concentration:

Feedstock is normally concentrated prior to introduction into the spray dryer.

 

(ii)   Atomization:

The atomization stage creates the optimum condition for evaporation to a dried product having the desired characteristics.

 

(iii) Droplet-air contact:

In the chamber, atomized liquid is brought into contact with hot gas, resulting in the evaporation of 95%+of the water contained in the droplets in a matter of a few seconds.

 

(iv)  Droplet drying:

Moisture evaporation takes place in two stages-

1)    During the first stage, there is sufficient moisture in the drop to replace the liquid evaporated at the surface and evaporation takes place at a relatively constant rate.

2)    The second stage begins when there is no longer enough moisture to maintain saturated conditions at the droplet surface, causing a dried shell to form at the surface. Evaporation then depends on the diffusion of moisture through the shell, which is increasing in thickness.

 

(v)   Separation:

Cyclones, bag filters, and electrostatic precipitators are used for the final separation stage. Wet Scrubbers are

 

 

often used to purify and cool the air so that it can be released to atmosphere.

 

Advantages of Spray Drying⁵:

·        Able to operate in applications that range from aseptic pharmaceutical processing to ceramic powder production.

·        Powder quality remains constant during the entire run of the dryer.

·        Operation is continuous and adaptable to full automatic control.

·        Nearly spherical particles can be produced.

·        It can be designed to virtually any capacity required. Feed rates range from a few pounds per hour to over 100 tons per hour.

·        Can be used with both heat-resistant and heat sensitive products.

·        Feedstock can be in solution, slurry, paste, gel, suspension or melt form.

·        Product density can be controlled.

·        Material does not contact metal surfaces until dried, reducing corrosion problems.

 

Disadvantages of Spray Drying:

·        It is not typically well suited for producing granules with mean particle size>200 mm.

·        It also has poor thermal efficiency at lower inlet temperatures and the exhaust air stream contains heat, which often requires sophisticated heat exchange equipment for removal.

 

Instrumentation^{1, 6, 7, 8}:

A)    Atomizers:

The "heart" of any spray dryer is the atomizer, small in size, big in importance, installing the right atomizer is essential to spray drying success.

 

Following are the ideal requirements of an atomizer used in the spray drying process:

1     It must disperse the feed material into small droplets, which should be well distributed within the dryer and mixed thoroughly with the hot gas.

2     The size of the droplets produced must be compatible with the required product particle size characteristics.

3     The droplets produced must not be so large that they are incompletely dried, nor so small that product recovery is difficult. Small particles may also overheat and become scorched.

4     The atomizer must also act as a metering device, controlling the rate at which the material is fed into the dryer.

 

Table 1: Types of atomizers and their mode of atomization

Sr. no	Atomizer type	Mode of atomization
1	Rotary Atomizer	Centrifugal Energy
2	Pressure Nozzle	Pressure Energy
3	Two fluid nozzle	Kinetic energy

 

Table 2–Median droplet size of different atomization devices

Atomization device	Median Droplet Size (µm)
Rotary atomizer (wheel)	10–200
Pneumatic nozzle (two/three- fluid)	5–100
Pressure nozzle	30–350

 

a)     Rotary atomizer:

In Rotary atomizers the liquid is continuously accelerated to the wheel edge by centrifugal forces, produced by the rotation of the wheel. The liquid is distributed centrally and then extends over the wheel surface in a thin sheet, discharged at high speed at the periphery of the wheel. The degree of atomization from a rotating disc atomizer depends on the disk peripheral speed, feed rate, feed physical properties, and atomizer design. This degree of atomization in turn affects various properties of the finished product. Rotary atomizers normally operate in the range of 5000–25,000 rpm with wheel diameter of 5–50 cm.

 

b)     Pressure nozzle:

The basic function of pressure nozzles is to convert the pressure energy supplied by the high pressure pump into kinetic energy in form of a thin film, the stability of which is determined by the properties of the liquid such as viscosity, surface tension, density and quantity per unit of time, and by the medium into which the liquid is sprayed.

 

c)      Pneumatic nozzles:

In these nozzles, the liquid mass is atomized using high air velocity leading to formation of friction forces and thus, breaking the liquid mass into tiny droplets. Droplets formation using these nozzles is done in two stages; the first stage involves transformation of the liquid feed into coarse droplets and the second stage involves transformation of the coarse droplets into tiny droplets. Rheological properties of air and feed such as surface tension, density and viscosity determine the product final quality. Fouling and clogging problems are observed at these systems.

 

B)     Air flow:

Once the liquid is atomized it has to come into contact with drying air for evaporation to take place. This is done in a drying chamber. There are various modes of contact which influence the evaporation rates and product temperatures in the dryer. Following are the various configurations of the modes of contact.

 

a)      Co-current flow: in a co-current dryer, the spray is directed into the hot air entering the dryer and both pass through the chamber in the same direction.

b)     Counter-current flow: in this dryer design, the spray and the air are introduced at opposite ends of the dryer, with the atomizer positioned at the top and the air entering at the bottom.

c)      Mixed flow: dryers of this type combine both co-current and counter current flow. In a mixed flow dryer, the air enters at the top and the atomizer is located at the bottom.

 

C)    Drying Chambers:

Spray drying chamber Air within the chamber maintains a flow pattern, preventing deposition of partially dried product on the wall or atomizer. Air movement and temperature of inlet air influence the type of final product. Various designs of drying chambers are seen on the market. The most common one is the cylindrical chamber with a cone of 40-60º, where gravity forces the powder to leave chamber. The drying chambers with a flat bottom require a scraper or suction device to remove the powder fraction from the chamber.

 

Recovery System⁹:

Regarding that hot air exited from spray dryer contains some dried tiny particles, it is necessary to separate these particles from the hot air. To achieve this aim, cyclonic separating systems based on centrifugal force are used. Efficiency of powder separation from the air is influenced by the mixture (powder and air) inlet shape as well as the cyclone number and dimension. Air and powder mixture inlets into the cyclone are in the shape of wrap-around and tangential.

 

D)    Cyclone Separators:

Two systems are employed in separating the product from the drying medium: the primary and secondary separation. Note that the spray drying chamber often has a conical bottom to facilitate the easy collection of the dried powder. During the primary separation, the dry powder is collected at the base of the dryer, followed by removal using a screw conveyor or a pneumatic system with a cyclone separator at the time of secondary separation. The gas stream loaded with the evaporated moisture is drawn from the centre of the cone above the conical bottom and is discharged through a side outlet. The relatively low efficiency of collection necessitates the use of an additional particle collection system, comprising dry collectors followed by wet scrubbers. The dry collectors include a cyclone separator, a bag filter and an electrostatic precipitator, depending on the size of the particles carried away by the exhaust gas and the final product specifications.

 

E)     Bag filter:

The bag filter comprises a metallic housing designed for continuous operation and automatic cleaning. The particle‐laden air enters under suction or pressure through the collector in the center or bottom part (i.e. the hopper) of the bag filter. The air, with particles, travels through the filter bag, which retains the product particles on its surface. The clean air passes out through bags and plenum to the outlet of bag filter. Accumulation of dust on bags causes an increase in the differential pressure across the filter bags. Compressed air is pulsed by a timer‐actuated series of normally closed pulse valves at preset intervals, causing the valves to open. The compressed air is stored in a reservoir located beside the higher filter chamber. Above each row of bags there is a tube with holes that are aligned with the central air passage gap, located on top of the bags, through which compressed air is injected to invert the gas flow momentarily. This causes the particulate material accumulated outside the bags to be removed.

 

Classification of Spray Dryers¹⁰:

Spray dryers can be classified into various types based on the type of cycle, type of stage and based on position.

 

1)     Classification based on the type of cycle:

a)     Open cycle dryer:

In an open cycle dryer, drying air is drawn from the atmosphere, heated, conveyed through the chamber and then exhausted to the atmosphere. This is by far the most commonly used design.

 

b)     closed cycle spray dryer:

Closed cycle dryers work on the principle of recycling and reusing the gaseous medium, which is usually a relatively inert gas such as nitrogen, or air in special cases. A closed cycle dryer is used when the feedstock is prepared by dissolving the solids in flammable sol- vents, in order to reduce the explosion risk and to obtain a complete recovery of the solvent. When the spray dried product is susceptible to oxidation, then a closed cycle dryer is the most appropriate choice. It is also advantageous to use this type of dryer when a toxic feed is subjected to drying, and the resultant pollution due to noxious vapors and undesirable particulate emissions or odor are not permitted by the regulatory norms. However, these conditions are normally not encountered in a food industry.

 

c)      Semi Closed spray dryer:

This design is a cross between open and closed cycle dryers and it is not gas tight. There are many variations on this design, with the most important being the “direct heated” or “self-inertizing” system. In the self-inertizing design, a direct-fired heater is used and the air entering the system is limited to that required for combustion. An amount of air equal to handling involved during the separation stage. Excessive mechanical handling can produce powders with a high percentage of fines.

 

2)     Classification based on the type of stage:

Single‐stage spray dryer:

The single‐stage configuration is the most predominantly used spray dryer design. In a single‐ stage dryer, the moisture is reduced to the target level in a single pass through the spray chamber. The single‐stage spray dryers operate at an inlet temperature of 150–200°C and an outlet temperature of around 95°C. However, if lower residual moisture content is expected of the final product, and then the relative humidity of the outlet air should be lower, hence, the outlet temperature should be higher. The resultant particle temperature would therefore be higher, which is not suitable for heat‐sensitive products. Furthermore, warmer temperatures would possibly cause the particles to stick together with very weak bindings to form large and loose agglomerates. At extremely high outlet air temperatures, blow‐hole formation might occur.

 

Two stage dryer:

Two stage dryers allow the use of lower temperatures in the dryer, making the design a good choice for products that are particularly heat sensitive.

 

Ten Guidelines of Spray Drying Process Parameters⁷:

1.    The inlet temperature must be as high as possible in order to achieve a final product with low residual moisture and a higher thermal efficiency (choice of inlet temperature should take into account the heat sensitivity of the feed components to prevent thermal degradation).

2.    Increasing the feed flow rate lowers the outlet temperature and thus increases the temperature difference between the inlet temperature and the outlet temperature. This results in product with higher residual moisture content.

3.    High aspirator speed leads to higher degree of separation in the cyclone.

4.    Lower aspirator speed leads to lower residual moisture content.

5.    The higher the feed flow rate, the larger is the size of the particles in the final product.

6.    The higher the feed concentration, the greater is the moisture content of the particles and, hence, the greater the possibility of agglomeration and the occurrence of irregular particle shapes.

7.    The drying air temperature should be below the glass transition temperature in order to prevent product collapse and stickiness in the spray chamber.

8.    The Tg of the feed material can be made higher for a convenient spray drying operation by the addition of high molecular weight components such as maltodextrin.

9.    The percentage of water content in the feed is also a significant parameter in controlling the Tg, since water depresses Tg considerably.

10. A shorter residence time (RT) (10–15 sec) is recommended for fine particles containing an ample amount of free surface moisture content, enabling easy evaporation. A medium RT (25–35 sec) should be applied for fine to semi‐coarse sprays that needs to be dried to low residual moisture content. A longer RT is needed for drying coarser sprays in order to achieve lower residual moisture content.

 

Applications of Spray Dryer in Pharmaceutical Field^11,12,13.:

1)     Effect of spray drying on powder properties:

Many spray drying operations produce spherical particles while others result in non-spherical particles. Particles may be hollow or solid. Pressure spray nozzles can produce particles ranging in size from 20 to 600 microns.

 

2)     Encapsulation:

A microcapsule can be either an individually coated solid particle or liquid droplet, or a matrix containing many small, fine core particles. Matrix microcapsules containing drug substance and a biodegradable polymer are usually prepared by spray drying in order to obtain controlled drug release formulations.

 

3)     Directly compressible powder:

Spray drying can be used to modify the size distribution, crystal habit, crystallinity content, polymorphism and moisture content if particles resulting in improved compactability.

4)     Bioavailability enhancement:

Spray drying can be used to enhance the solubility and dissolution rate of poorly soluble drugs. This usually occurs via the formation of pharmaceutical complexes or via the development of solid dispersions.

 

5)     Application in Primary Pharmaceuticals and excipients:

Active pharmaceutical ingredients are typically produced by extraction or chemical synthesis. In most cases the material is subsequently crystallized, mechanically separated. These steps are often replaced by spray drying. which not only helps control the residual moisture content in the powder but also to create materials with a tailor made particle size distribution, morphology and nature.

 

6)     Aseptic Production(vaccines):

Spray drying offers a number of advantages over traditional methods of aseptic drying such as freeze drying. Producing stabilized vaccines using spray drying reduces the need for refrigeration and makes their transport and storage far easier.

 

7)     Spray chilling :

Also called spray congealing or spray cooling it is a similar method to spray drying, but with different ‘thermodynamic sign’. The same basic equipment as spray chilling is used as with spray drying although no heat is required. In this process, a drug substance is allowed to melt, disperse, or dissolve in hot melts of waxes, fatty acids, etc., and sprayed into an air chamber, where the temperature is below the melting temperatures of the formulation components, to provide spherical congealed pellets under appropriate processing conditions.

 

8)     Flowability and Size Reduction:

Solid dosage pharmaceuticals often require a separate granulation step in the production cycle to avoid segregation and to produce a powder that has the correct flow properties to accommodate a high-speed tablet press. However, in the case of spray drying, granulation can be made an integral part of the continuous process. This not only results in a more streamlined, efficient production process, but reduces costs too.

 

9)     Inhalation:

The delivery of therapeutic macromolecules by inhalation, however, presents additional problems and challenges to produce fine powders of particle size 0.5 mm–5 mm that flow well during manufacture, filling, and emptying from the inhaler device, but now highly specialized spray drying nozzles have been developed that help to achieve far greater particle engineering capabilities, even at a large scale, making it possible to accurately manipulate aerodynamic particle size and flow properties.

 

10)  Dry powder aerosols and heat sensitive materials:

Spray drying is an excellent method for the production of dry powder formulations since particle size distribution and residual moisture content of the spray dried powders can be easily controlled by the process conditions. In addition, the processing of heat sensitive materials is feasible because the cooling effect caused by the solvent evaporation. Hence, the actual temperature of the dried product is far below the outlet temperature of the drying air.

 

11)  Complex formation:

To increase the solubility and bioavailability of poorly water soluble drug substances, Cyclodextrins can be used.

 

CONCLUSION:

Spray drying is a process of suspending sprayed particles and removing the particles moisture by hot air. Quality of spray-dried products is high due to the protection of the particles through evaporative cooling during the process. Spray drying is presently one of the most exciting technologies for the pharmaceutical industry, being an ideal process where the end-product must comply with precise quality standards regarding particle size distribution, residual moisture content, bulk density and morphology. Overall, spray drying has a bright future due to its versatility, efficiency and the driving force of poorly soluble drugs.

 

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Received on 17.02.2018                Accepted on 15.03.2018               

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