The control panel of the tanker at the Bionorica site is bright orange. The number 33-1170 shines on it in black. The tanker is carrying a highly concentrated cargo: 1170 stands for alcohol in its purest form. The delivery papers say "ethanol 96% as defined by the European Pharmacopeia."

Such deliveries are not unusual for Bionorica. "In addition to herbal raw materials, water and ethanol as solvents are among our most important starting materials," says Dr. Joachim Erler, Head of Production at Bionorica. Every liquid dissolves different substances from plants. The polarity of the solvent determines which ones are dissolved. Water, for instance, is relatively polar, while hexane is an unpolar substance. Ethanol is somewhere between the two.

 

Experts at Bionorica use pure water to extract substances from marshmallow roots or lovage. However, a great amount of alcohol is necessary, if it is a question of extracting polyphenols, flavones, flavonoids or essential oils. 70-percent alcohol and 30-percent water are used to obtain plant constituents from ivy.

As with the alcohol, the water used for extraction purposes also has to meet the strict requirements of the European
Pharmacopeia. Bionorica produces some 20,000 liters of "Aqua purificata" daily by leading normal tap water through activated carbon filters and a reverse osmosis system and then exposing it to ultraviolet light to eliminate all germs.

The precise composition of the extraction agent is specifically defined for each preparation and on file with the registration authorities. Users find the relevant information on the package insert under "extraction agent." How much extraction agent is required to obtain a certain amount of active ingredient is also specified. The temperature plays a decisive role as well. "The hotter the extraction agent, the more effective the extraction will be," says Erler. However, the risk of destroying valuable substances also rises with increasing temperatures. Boiling water ? in other words, at a temperature used to make tea or coffee - cannot be used to produce phytopharmaceuticals because many important plant constituents react very sensitively to heat. For this reason, one has to reduce the temperature in production, and this requires patience. "As a general rule, lowering the temperature by 10 degrees means that extraction will take twice as long," says Erler. And so some processes last up to 20 hours.

The exact description of the process is laid down in the company's own BNO nomenclature. "This BNO classification attests to the uniqueness and consistent quality of our products. These are quality seals for our unique special extracts," explains Professor Michael Popp. The CEO of Bionorica has absolutely no doubts that these are truly "high-tech products," not least because of the highly sophisticated extraction processes that are, in many cases, patented by Bionorica. Popp: "Our Engineering Department already began setting standards in 1988. The extraction facilities have since been completely redesigned and reconstructed. We also have implemented a fully automatic computer-controlled quality control system.?

The same goes for Bronchipret. Maceration is the name of the process used to extract important constituents from ground thyme leaves. The extraction agent is circulated in the closed system of the 2200-liter V4A stainless steel extractor filled with thyme. Measuring and control devices monitor the process. With their various valves and sieves, they regulate throughput and circulating volume. Heat exchangers help keep the temperature below 25° Celsius. Special software allows all process data to be recorded, regulated and documented. Samples are regularly submitted for laboratory testing. It takes some four hours to obtain the liquid thyme extract. But this substance is still a long way from becoming a finished medicine. The liquid must rest in a stainless steel tank for three more days so that the coarse floating particles can settle. The finer grains are separated by means of deep and membrane filtrations. The resulting filtrate is the basis for Bronchipret syrup and drops.

A different method is used to produce Bronchipret tablets. "We need dried extract for these products, which means that we have to remove the extraction agent completely." This is a task easier said than done. Here, too, proprietary know-how plays an important role.

The first step is the careful concentration in a plate evaporation unit. The extract flows over plates kept at the perfect temperature so that the liquid is carefully sucked up under a slight vacuum. As soon as the concentration of solids reaches 50 percent, the next step follows. The solid concentration is increased to 70 percent in a vacuum evaporator. Experts call the resulting, relatively viscous paste spissum or thick extract. To separate the remaining extraction agents, Bionorica uses a vacuum drier that was developed in-house. This process received the German Innovation
Award and has been patented worldwide. Extremely low pressure is produced by high-performance vacuum pumps. As the boiling point sinks, the liquid evaporates. An elaborate anchor agitator ensures that the unwieldy and highly viscous paste is kept in motion long enough for the remaining water and ethanol molecules to evaporate. Even now, the temperature must be kept below 40° C - otherwise the thymol, for instance, could decompose.

Vacuum drying of thyme takes eight hours. A fine powder remains in the apparatus. From here, the powder is taken to the laboratory for quality control. Does it contain all the valuable herbal constituents? Are the consistency and residual moisture correct? Only then will the dried extract receive the quality seal BNO 1565, and the next chapter can begin: production of film-coated Bronchipret of the highest quality.