Freeze drying or lyophilization is applied to pharmaceutical research, development, manufacturing, and transport. Lyophilization in the development of biopharmaceuticals revolves around the process of sublimination, by which proteins, antibodies, or other drug and drug-related substances are converted from a solid phase directly to a gaseous phase. Freeze drying is commonly employed to overcome barriers to stability in labile products and common uses of lyophilization are seen in the creation and storage of room temperature products. Freeze-dried products’ extended shelf lives provide benefits for research and manufacturing.

Pharmaceutical Freeze Drying Process

Lyophilization involves freezing a substance and then removing any ice or solvent through sublimation, which turns it into vapor without passing through a liquid stage. This requires specialist equipment. There are three stages to the process:

1. FREEZE – The sample is completely frozen, typically in a glass vial or flask.
2. VACUUM – This requires a deep vacuum which is significantly below the triple point of water (the lowest point where liquid, gas and solid forms of the material can coexist).
3. DRYING – Energy in the form of heat is added, which causes sublimation.

Compared to other methods of product preparation, controlled lyophilization keeps the product at a low enough temperature to avoid changes in the characteristics and appearance of the dried product. This makes it a good method for the preservation of many different heat-sensitive materials. These include microbes, proteins, pharmaceuticals, plasma, and tissues.

Advantages of Freeze Drying Pharmaceuticals

With freeze drying, delicate, unstable or heat-sensitive drugs and biologicals can be dried at low temperatures without damaging their physical structure. Freeze-dried products can be reconstituted quickly and easily, which is particularly valuable in the case of emergency vaccines and antibodies, which need to be administered as quickly as possible.

Freezing alone has some major disadvantages:

• Maintaining frozen storage is costly and takes up a lot of space
• Transportation of frozen materials can be difficult and expensive
• Failure of freezing equipment would risk the total loss of the product

Conventional drying methods also have a major disadvantage as the high temperatures used can cause chemical or physical changes to the product. For pharmaceuticals and bio-products, this would cause a reduction in biological activity, which could render them ineffective.

Pharmaceuticals and Biologicals Suitable For Freeze Drying

Pharmaceutical companies often use freeze-drying to increase the shelf life of the products, such as live virus vaccines,biologics and other injectables. By removing the water from the material and sealing the material in a glass vial, the material can be easily stored, shipped, and later reconstituted to its original form for injection. Another example from the pharmaceutical industry is the use of freeze drying to produce tablets or wafers, the advantage of which is less excipient as well as a rapidly absorbed and easily administered dosage form.

Freeze-dried pharmaceutical products are produced as lyophilized powders for reconstitution in vials and more recently in prefilled syringes for self-administration by a patient.

Examples of lyophilized biological products include many vaccines such as live measles virus vaccine, typhoid vaccine, and meningococcal polysaccharide vaccine groups A and C combined. Other freeze-dried biological products include antihemophilic factor VIII, interferon alfa, anti-blood clot medicine streptokinase, and wasp venom allergenic extract.

Many bio-pharmaceutical products based on therapeutic proteins such as monoclonal antibodies require lyophilization for stability. Examples of lyophilized biopharmaceuticals include blockbuster drugs such as etanercept (Enbrel by Amgen), infliximab (Remicade by Janssen Biotech), rituximab, and trastuzumab (Herceptin by Genentech).

Freeze-drying is also used in manufacturing of raw materials for pharmaceutical products. Active Pharmaceutical Product Ingredients (APIs) are lyophilized to achieve chemical stability under room temperature storage. Bulk lyophilization of APIs is typically conducted using trays instead of glass vials.

Cell extracts that support cell-free biotechnology applications such as point-of-care diagnostics and biomanufacturing are also freeze-dried to improve stability under room temperature storage.

Dry powders of probiotics are often produced by bulk freeze-drying of live microorganisms such as lactic acid bacteria and bifidobacteria.