Drying

Drying is the process of removing the presence of solvents (i.e. water or other liquids) in a formulation with the presence of heat. The final product of this unit operation is a dry solid mass or powders. This process is widely used in the pharmaceutical field, from research and development phase until large-scale manufacture.

It is important to have a good understanding of this process’ impact on the quality attributes of the active pharmaceutical ingredient (API) in order to guarantee it will not have any adverse impact on the drug’s safety and efficiency, thus, providing high quality final products.

All drying processes of relevance to pharmaceutical manufacturing involve evaporation or sublimation of the liquid phase and the removal of the subsequent vapour.

Different Methods of Drying

Drying of Wet Solids: Convective Drying of Wet Solids: This method utilizes dynamic convective dryers (e.g., Fluidized-bed dryer) to obtain good contact between the warm drying air and wet particles in the fluidized-bed dryer.

The fluidized-bed dryer was developed for the process of fluidization to improve the efficiency of heat transfer and vapor removal, as compared with the older static tray dryers. This fluidized-bed dryer also allows the efficient transfer of the latent heat of evaporation from the air and into the drying solid.

Advantages of fluidized-bed drying:
- Shortens drying time via the efficient heat and mass transfer, allowing high product output with small footprint.
- Minimizes heat challenge to thermolabile materials
- The turbulence in a fluidized bed causes some gnaws the surface of the granule, thus, producing a more spherical free-flowing product.
  - Conductive Drying of Wet Solids: In this process, the wet solid is in thermal contact with a hot surface and the bulk of heat transfer occurs by conduction.
    
    A good example is the vacuum oven, though it is not used as extensively as before. The vacuum oven consists of a strongly constructed jacketed vessel that can withstand a vacuum within the oven and possibly steam pressure in the jacket. Moreover, the supports for the shelves form part of the jacket, giving a larger area for conduction heat transfer.
    
    The main advantage of a vacuum oven is that drying takes place in a low temperature with minimum oxidation risk due to only a small amount of air present. Although the overall temperature of the drying solid can rise to the steam or heating water condition, it is not usually harmful.
    
    Vacuum ovens are rarely used nowadays for production but for thermolabile materials, using such equipment may be the only viable option.
  - Radiation Drying of Wet Solids: This process allows heat transmission through radiation. This method differs from heat transfer by conduction or convection such that, no transfer medium (solid, liquid or gaseous) is present during the drying process. Instead, this method takes advantage of heat energy’s ability, in the form of radiation, to cross empty space and virtually travel through the atmosphere without loss. Once this energy falls on a body capable of absorbing it, heat appears; although a proportion may be reflected or transmitted.
    
    Microwave radiation in the wavelength range 10 mm to 1 m has been found to be an efficient heating and drying method, as such, these dryers are used in the pharmaceutical industry.
    
    Advantages of microwave drying includes:
    - Rapid drying at fairly low temperature
    - Highly efficient equipment
    - GMP compliant design
    Certain disadvantages for microwave drying involves the need for radiation shielding in order to prevent organ (eyes and testes) damage. However, the use of ‘fail-safe’ devices guarantee operator protection as this ensures microwave generation is prevented until the drying chamber is sealed.
Drying for Solutions and Suspensions

Main objective for this process is to create a large surface area, with the liquid, that will allow heat and mass transfer; this provides an efficient way to collect the dry solid particles.

Spray drying is the most useful method for drying solutions and suspensions as it disperses the liquid to a spray of small droplets. This operation uses a spray dryer which atomizes the liquid into smaller droplets, thus, creating a large surface area for heat and mass transfer. These are sprayed into a stream of hot air, so that each droplet dries to an individual solid particle. Thus particle formation and drying occurs.

Spray drying can be used for almost any substance in solution or in suspension. However, it is most beneficial for thermolabile materials – especially if continuous handling of large quantities of the substance, is required.

A development in spray drying is the use of fluidized spray dryer. This is composed of a small fluidized bed that is mounted at the base of the cone – the point where the product is collected. The presence of moving air in the fluidized bed dryer, overcomes any cohesion of spray-dried particles after they fall into the collection chamber. Thus, allowing handling of spheres with higher moisture content; even those substances that are stickier and more cohesive than were previously possible to process. Examples of both soluble and insoluble substances that are spray dried include citric acid, gelatin, starch, and calcium phosphate.

The process is also used for some powdered antibiotic formulations where the spray-dried powder is packaged and distributed. This is then reconstituted as a syrup at the time of dispensing.

Spray drying is also capable of producing spherical particles in the respirable range of 1-7μm that are necessary for the delivery of drugs from dry powder inhalers.
Freeze Drying

Freeze drying is a process used to dry extremely heat-sensitive materials as it allows drying without the excessive damage to substances such as: proteins, blood products, and even microorganisms (with a small significant viability).

In this unit operation the initial liquid solution or suspension is frozen through the process of sublimation; the phenomenon that causes direct vaporization and condensation of a solid without the need to form an intermediate liquid phase. This is done by reducing the pressure above the frozen state.

Advantages of the Freeze Drying process:
- Minimized chemical decomposition by inhibiting enzyme action since drying takes place at very low temperatures.
- Minimized oxidation as the process takes place under high vacuum with little contact with air.

Packaging of freeze-dried products must ensure protection from moisture during storage. Container closures must ensure no contact with the atmosphere, example of which is the sealing of ampoules while still under vacuum. Otherwise, the closing must be carried out under controlled atmospheric conditions. Take note that the dry material often needs to be STERILE.

There are different methods of drying, the use of which are dependent on the specific characteristics of the APIs and excipients that will be used in the formulation or manufacture of the final drug product.

Different dryer technologies also come with design variations, including containment and control of possible vapor and dust generation. For contained dryers, it is important to understand the nature of substances to be handled as some may pose explosion incidents and therefore should have an ATEX rated or explosion proof venting or overall mechanical design.

Barrier technologies to enclose the drying process may also be employed. Modern technologies allow the integration of other mechanical equipment that can assist workers during heavy lifting activities.

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