Spray drying is method of dehydrating fluids, solutions and thin slurries, it converts the fluids or slurries to powder form. Liquid or slurry material to be dehydrated is sprayed in the form of a fine droplet dispersion into hot airstream. Both air and material either travel in parallel or counterflow. Drying in spray dryer occurs at very fast rate so that the contact of material to heat is not for longer time hence its does not damage the heat selectivity materials and becomes ideal for drying such materials.

Spray drying is one of the most remarkable technologies currently to be applied to pharmaceuticals. It is a continuous process that converts, in a single step, a liquid feed into a powder and is an ideal process when precise attributes such as particle size, morphology and stability are required. This review describes the technology, current and future applications and how the present level of understanding and modeling tools enable a process development stage that is both lean and risk-free.

Spray drying in the pharmaceutical industry

The use of spray drying in pharmaceuticals was first explored by Bullock and co-workers in the 1940s and applied to infusions, extracts, inorganic medicinal salts, adrenaline and vitamin C. Many more applications followed, and particularly relevant was the production of pharmaceutical excipients and the isolation of active ingredients that were either thermal-sensitive or difficult to crystallise. Contrary to common perception, spray drying is in fact a very gentle drying method – firstly, the exposure to temperature is limited to seconds or at most a few minutes, and secondly, the cooling effect that results from the evaporation process protects the spray dried materials from the higher bulk temperatures. But despite the multiplicity of uses, it was not until the turn of this century that the use of spray drying in pharmaceutical applications increased significantly.

The key driver for this expansion was the need to formulate oral drugs in the amorphous state as a means to increase the bioavailability of many modern drugs. Due to spray drying’s rapid evaporation process this has become an ideal way to precipitate drugs from solutions in an amorphous state. This formulation platform, known as “amorphous solid dispersions”, is the fastest growing formulation approach to overcome the poor bioavailability of many drugs. Spray Drying and Hot Melt Extrusion are the main manufacturing process to obtain these amorphous materials. Other drivers for the more widespread use of spray drying in the pharmaceutical industry include the production of inhalable drugs such as Pfizer’s Exubera or Mannkind’s Afrezza (both inhaled powder insulin), microcapsules for controlled-release formulations or taste masking and advanced powder forms such as direct compressible and readily wet-able powders. So it is no surprise to see that every two years, or more recently every year, a new chemical entity is formulated using spray drying technology. Some examples of some of these include Cesamet (nabilone, Valeant Pharmaceuticals), Intelence (etravirine, Janssen Therapeutics) and Incivek (telaprevir, Vertex Pharmaceuticals). The enabling features of spray drying are also being applied in the reformulation of existing drugs and for life cycle management purposes.

Equipment types and scales

Spray dryers differ in many different ways: for example, whether or not the drying gas recirculates (close vs. open loop systems), the type of drying gas utilised (air, nitrogen or argon), the type of atomiser or nozzle (pressure, two-fluid, ultrasonic or rotary), the powder recovery system used (often through a cyclone and/or a filter bag), the degree of finishing (namely the level of polish of the internal surfaces), the existence or not of clean-in-place (CIP) or sterilisation-in-place systems as well as the level of instrumentation and automation.

Pharmaceutical spray dryers often combine the highest degree of finishing and the most sophisticated control systems with the simplest hardware designs that provide for easier cleaning. In many cases nitrogen is the preferred drying gas to air, not only because it allows the safe drying of organic solvents but also to reduce oxidation in the product. Pressure and two-fluid nozzles are mostly used in pilot and large scale equipment and their selection often depends on the type of feed and the target particle size of the final product. Rotary nozzles are less often used due to poor cleanability. Very interesting is the use of ultrasonic nozzles in small scale equipment since they allow for the formation of large droplets which very closely resemble those of larger equipment.

For amorphous solid dispersions, close system spray dryers using nitrogen as the drying gas are typically used because of the need to handle organic solvents.

Pressure nozzles are also favoured because they result in powders with better flow characteristics (as a result of the narrower particle size distribution), which simplifies the downstream processes of tableting or capsule filling.

Spray dryers in the pharmaceutical industry are available in a wide range of scales: from lab units where a gram or less of final material can be produced, to very large commercial units capable of producing several tons per day.

Future applications for spray drying in pharmaceuticals

Spray drying as an enabling technology for poorly soluble oral drugs is likely to continue to grow as amorphous materials become more established and widely accepted by the industry. However, future and sizable growth is likely to come from its application in biopharmaceuticals such as in the isolation and preparation of peptides, proteins and monoclonal antibodies. The cost and throughput advantage over traditional lyophilisation and the ability to deal with far more complex formulations and solvent systems is likely to drive its gradual introduction in these fields. Aseptic spray dryer is still in the early stage of implementation but robust steps have recently been undertaken in the design of these units as well as in aseptic powder filling, a complementing unit operation. Another area of potential growth is the use of spray drying to produce inhalable drugs; one of the major drawbacks associated with conventional lactose blends is the need to balance adhesive-cohesive forces between the drug and the carrier, with a significant amount of drug not detaching from the lactose and being inevitably deposited in the mouth/throat; spray drying can be used to overcome this challenge by enabling the preparation of composite particles where, via a precise fine-tuning of particle size distribution during development (and tight control during manufacturing), very high and reproducible respirale fractions can be obtained.

Spray Drying for Fortification

There is often a need to provide nutrients that otherwise would or could not be consumed readily, and that’s when fortification comes into play. If you are lacking Vitamin D3 and cannot be out in the sunlight for significant time, then the best way to get it is through a supplement or a fortified product. To get a fat-soluble such as Vitamin D3 into a product, spray drying is a technique that could be used. Spray drying, simply stated, allows D3 crystals to be dissolved/suspended into an oil phase, then mixed with a carrier such as maltodextrin or gum arabic, and then spray dried to remove the water under heat, thus resulting in a spray dried D3 powder. By converting the crystals into usable powder form, this powder can now easily be added into products that need to be fortified, enabling your product to achieve your targeted Recommended Daily Value.

Spray Drying to Change Physical Appearance

There are many products that can be spray dried, and some of those include beta carotene, cheese powders, juices, and seasonings. Beta carotene is an ingredient that has a red/pink hue that can present challenges for food manufacturers that do not necessarily want the color to impact their food or beverage product. So what can be done about this? Watson has developed a spray dried beta carotene product that, when dissolved in water, is clear!  It’s called BetaClear® 768, and can tremendously help a food manufacturer to utilize beta carotene to meet Vitamin A claims without seeing a color impact in their finished product.

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