Go lyophilization


Lyophilization (from the Greek. Lyo - dissolve and philia - aptitude) - drying in vacuum of pre-frozen biological preparations, thermolabile compounds and food products. It is used as a laboratory method in microbiology for preserving bacteria and viruses for a long time in order to create “museums” of cultures, in histochemistry for fixing and preserving histological preparations. It is widely used in the medical industry in the production of medical, prophylactic and diagnostic products - vaccines and serums, antibiotics, canned blood products (dried plasma for transfusion, blood substitutes), as well as for creating “banks” of dry preparations (homocausty, homogenous, homosudov) used during surgical operations. Lyophilized preparations can be stored for a long time; they are insensitive to temperature fluctuations during storage, easily transferred to the native state after the introduction of the solvent (water, saline).

Lyophilization consists of pre-freezing and freeze drying. Preservation of the drug is carried out during freezing with the hardening of the liquid phase (medium); almost all biochemical, chemical and physical processes are suspended. For microbiological and viral preparations, the medium is selected in such a way as to prevent the possible destruction of individual cells during the solidification of the solution and the formation of ice. Such media usually consist of a combination of a crystalloid and a colloid (for example, a sucrose-gelatin medium).


Tissue preparations require a special selection of freezing modes, since the introduction of any media into such preparations is usually unacceptable. The main requirement for freezing modes of tissue preparations is that mechanical damage to the cell membranes and membranes by the resulting ice crystals does not occur, and also to prevent the fractionation of solutions inside and outside the cells, which is observed during the slow freezing of complex protein salt solutions. The final temperature during freezing should be below the point of solidification of the most low-melting fraction of the drug. At very high freezing rates, achievable only in thin sections or finely sprayed liquid, crystallization does not have time to occur and the water turns into a solid (amorphous) state without crystallization (vitrification). In this way, it is possible to obtain histological and tissue preparations that completely restore the native properties after deconservation.

In laboratories, freezing is carried out in mixtures of ice with salt, dry ice with alcohol or acetone, in liquid nitrogen; in industry, low-temperature refrigerated cabinets with forced air circulation, lari with brine, cooled to low temperatures are used. The highest freezing rates are achieved with the rapid cooling of thin films or sections placed in a contact low-melting liquid (for example, isopentane) cooled with liquid nitrogen.

In the process of drying, water is removed by sublimation (ice directly passes into steam, bypassing the liquid phase). Drying goes in layers. In order to shorten the time of drying when freezing liquid preparations, they strive to obtain thin layers and a large surface; for this, the bottle or bottle with the material is slowly rotated around the horizontal axis in a bath with a cooling mixture. In this case, the material is frozen on the side walls of the vessel. Primary, obtained by freezing, the structure should not be disturbed during drying. For this, the temperature of the preparation during the drying process must be below the melting point of the most low-melting fraction of the preparation. Drying is carried out in special devices under vacuum (residual pressure less than 10 -1 —10 -3 mm Hg. Art.). The absence of air continuously pumped out by a vacuum pump ensures the unimpeded movement of steam from the evaporation surface to the absorber (chemical or cold trap). In connection with the absorption of large amounts of heat during the evaporation of ice, the temperature of the material being dried is maintained at the required low level without special cooling.

The ultimate goal of lyophilization is to obtain a drug with low residual moisture (less than 1% by weight of dry residue). The drying process consists of removing free water from the preparation and drying it — removing bound water. Bound water is removed poorly, so the drying is carried out at elevated temperatures (20 ° and above) and improving the vacuum in the system. In some cases, at this stage special chemical absorbers (P 2 O 5 ) and high-vacuum diffusion pumps are used in addition to the pumps and absorbers used in the free water removal stage. Dried products are stored in a sealed container - bottles, cans, ampoules - to prevent their moisture when in contact with moist air. Histological preparations, after drying, are impregnated with paraffin under vacuum and stored in paraffin blocks.

See also Drying.