In the freeze-drying and storage processes of food, drugs, and organisms, many factors (such as chemical composition, freezing rate, freezing and dehydration stress, glass transition temperature, residual moisture in dried solids, temperature and humidity of the storage environment, etc.) can affect the stability of the active components and even lead to deactivation. Numerous experimental studies have shown that, except for a few materials such as food, human plasma, and milk that can be directly freeze-dried, most drugs and biological products require the addition of appropriate freeze-drying protectants and additives to prepare a mixture before effective freeze-drying and storage can be carried out.
There are currently several classification methods for freeze-drying machine protectants:
1. Classification by relative molecular weight
(1) Low molecular weight compounds. It can also be divided into acidic substances, neutral substances, and alkaline substances.
(2) Polymer compounds. Mainly including albumin, gelatin, soluble starch, dextrin, meat juice, pectin, arabic gum, hydroxymethylcellulose, algae, as well as natural mixtures such as skim milk, serum, etc.
Regarding the mechanism of action of protective agents, it is generally believed that low molecular weight compounds play a direct role in the freeze-drying process, while high molecular weight compounds promote the protective effect of low molecular weight compounds. Therefore, when preparing protective agent formulas, low and high molecular weight compounds are generally used in combination.
2. Classified by the function and properties of protective agents
(1) Freeze drying protection. Substances that can prevent the denaturation of active components during freezing and drying processes.
(2) Filler. A substance that can prevent effective components from sublimating and escaping with water vapor, and shape effective components.
(3) Anti leveling agent. A substance used to prevent oxidation and deterioration of biological products during freeze-drying and storage processes. Such as vitamin D. Vitamin E, protein hydrolysates, sodium thiosulfate, etc.
(4) Acid base adjuster. Substances that can adjust the pH of biological products to the stable zone of active substances during freeze-drying and storage processes.
3. Classification by type of substance
Such as sugars/polyols, polymers, surfactants, nitrogen-containing acids, and salts.
In the freeze-drying formula, in addition to active components and solvents, multiple additives are also required. These additives, some referred to as protectants, some referred to as additives, and some referred to as excipients, but there is currently no unified term. The term excipients comes from pharmacy and originally referred to inactive excipients (such as arabic gum, box pulp, starch) that make up drug antigens, especially those added in drug mixtures with a large amount of liquid to give the mixture high stickiness for the preparation of pills or tablets. Later, the name of the excipient was expanded.
In the freeze-drying formula of biological products, some additives can only play a specific role, while others can play multiple roles simultaneously.