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.

所有与药物制造的干燥过程涉及蒸发或升华液相并除去随后的蒸气。

Different Methods of Drying

Drying of Wet Solids:湿固体的对流干燥：该方法利用动态对流干燥器（例如，流化床干燥器），以在流化床干燥器中的温热干燥空气和湿颗粒之间获得良好的接触。
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:在该过程中，湿固体是与热表面热接触，并且通过传导发生大部分热传递。
    
    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.
    
    真空烘箱的主要优点是，由于仅存在少量空气，干燥在低温下发生干燥，其最小氧化风险。虽然干燥固体的总体温度可能上升到蒸汽或加热水状况，但它通常不会有害。
    
    Vacuum ovens are rarely used nowadays for production but for thermolabile materials, using such equipment may be the only viable option.
  - 湿固体的辐射干燥：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兼容设计
    微波干燥的某些缺点涉及辐射屏蔽的需要，以防止器官（眼睛和睾丸）损坏。然而，使用“故障安全”设备保证操作员保护，因为这确保了防止了微波生成，直到干燥室被密封。
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.

喷雾干燥可以用于几乎任何物质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.

该方法还用于一些粉末状抗生素制剂，其中喷涂干燥的粉末包装和分布。然后在分配时将其重构为糖浆。

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.
冷冻干燥

冷冻干燥是一种用于干燥极其热敏材料的过程，因为它允许干燥而没有对蛋白质，血液制品，甚至微生物（具有小的显着活力）的物质过度损坏。

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:
- 通过在非常低温下干燥以来，通过抑制酶活作用最小化化学分解。
- Minimized oxidation as the process takes place under high vacuum with little contact with air.

冻干产品的包装必须确保储存期间的水分保护。容器封闭物必须确保没有接触气氛，其示例是安瓿的密封仍然在真空下。否则，必须在受控的大气条件下进行闭合。请注意，干燥材料通常需要无菌。

有不同的干燥方法，使用其取决于将用于最终药品的配方或制造中的API和赋形剂的特定特征。

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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