The chemical resistance and stability of pharmaceutical primary packaging can be improved by applying extremely thin, yet highly effective barrier layers. Vials with hydrophobic coatings are the latest coating products that schott offers.
Photo: SCHOTT/T. Hauser
Coatings Protect Sensitive Drugs
SCHOTT employs advanced coating techniques to make pharmaceutical packaging fit for the future.
The pharmaceutical industry invests billions towards research on new drugs. The objective is to come up with even better medicines that are more effective and easier to administer. However, before a physician or hospital can make use of a new substance, a number of obstacles must be overcome. Safety and quality are at the top of the list. Here, the respective approval processes can take years or even decades. But, researchers and the authorities not only scrutinize the drugs themselves, but also containers that come into direct contact with the active ingredients. These products are referred to as primary pharmaceutical packaging, in other words vials, syringes, cartridges and ampoules. In addition to aspects like product integrity and user friendliness, other important questions are how to package and store new active ingredients most effectively.
Undesired adsorption, i. e. when active ingredients become attached to their containers, or how to deal with so-called »extractables« are examples of issues that are currently of interest. These elements that are invisible to the human eye can detach themselves from the pharmaceutical packaging over time and can, thus, interfere with the effectiveness of the medication stored inside. ”This effect can be observed even with borosilicate glass of the highest quality,” explains Dr. Claudia Dietrich, Product Manager for Vials & Coating at SCHOTT forma vitrum. The application of extremely thin barrier coatings to the inside surface of the pharmaceutical container represents one very effective approach to improving the chemical stability of these packaging materials.
Here, five letters have really made a name for themselves in the industry: PIVCD, which stands for »Plasma Impulse Chemical Vapor Deposition«. This technique was further developed and patented in numerous countries by SCHOTT in the 1980s. The first mass application was in so-called cold light reflectors. When coated on the inside, these are capable of increasing the efficiency of halogen lamps quite considerably.
Plasma coatings are opening up new dimensions in the pharmaceutical industry, as well. Here, the high quality glass vials manufactured from Fiolax® glass tubing at eleven different SCHOTT forma vitrum production sites are the starting products. First, the finished vials are washed in a pharmaceutical washing machine and then dried inside an electric heat tunnel. Afterwards, the containers are placed inside the plasma reactor. In a cycle that takes approximately one minute, multiple vials can be coated at once. With the pulsed plasma technique, several layers of silicon dioxide molecules are applied to the inside surfaces of the containers. The entire layer is only 100 to 200 nanometers thick and, therefore, has no effect on the dimensions of the pharmaceutical container.
First, the pharmaceutical vials are washed and dried inside a special machine, before silicon dioxide layers are applied in thin layers only 100 to 200 nanometers in thickness inside a plasma reactor.
Photo: SCHOTT/T. Hauser
The coating that is applied as part of a validated and permanently inspected process reduces the adsorption of radioactive diagnostic products and proteins and improves the chemical resistance and stability of the packaging material. The coated vials manufactured by SCHOTT forma vitrum are particularly well-suited for use with active ingredients that are pH-sensitive, due to the fact that the pH factor can be kept stable, because »extractables« are avoided and the surface of the glass is not attacked. This means sensitive medications can be stored for longer periods.
The method has been scientifically tested as an effective diffusion barrier. For example, the leaching out of ions that occurs naturally in glass declines to levels that are below the detection limit.
SCHOTT has been coating containers that are sold on a global basis under the brand name SCHOTT Type I plus® at its site in Müllheim, Germany, since 1997. In recent years, these products have been experiencing strong growth, due to the increase in market demand. Vials with so-called hydrophobic coatings that are also manufactured using the picvd technique are the latest coating product. Initial samples of these products are currently being sent to interested customers. Hydrophobic, in other words, water-repellent coatings have an extremely smooth surface, a trait that can offer great advantages with lyophilized (freeze-dried) medicines. Lyophilization processes have been known for a long time. They are used to preserve coffee (instant coffee), for instance. In the field of pharmaceuticals, lyophilization is primarily used to extend the shelf life of highly sensitive biotechnology products. This is an important field for the future. After all, biomolecules are already being used today in over 50 percent of all product developments in the area of pharmaceutical therapy.
To pay tribute to this development, more and more pharmaceutical companies are building additional lyophilization facilities for these sophisticated products.
During freeze-drying, a medication is dehydrated to leave behind a type of powder. As soon as it is to be put to use with patients, it is introduced to water once again and then dissolved. This is mainly put to use in high quality ingredients, such as proteins, some of which are produced biotechnologically. The advantages of freeze-drying are that products are preserved for longer, their effectiveness remains stable and the highly effective and sensitive ingredients are better protected. Such preparations are used in oncology (the treatment of cancer), for example. ”The interests of both the pharmaceutical industry and patients alike are rather obvious. They are seeking to provide their valuable and costly medications with the highest possible protection and ensure that they remain effective for as long as possible,” says Dr. Dietrich.
Vials with hydrophobic coatings have such homogeneous surfaces that freeze-dried substances find it difficult to adhere to the inside walls of the vials. The result is not only an improved cosmetic look, but also that medications dissolve more quickly in water. Nevertheless, glass is not the only material that can be improved by using coatings. Polymers also offer interesting potential for optimization. Here, however, the picvd coating mainly improves the oxygen and water vapor barriers, an aspect that can open up new avenues for biopharmaceuticals, for example.
In vogue: coatings with organic molecules
SCHOTT forma vitrum works very closely with experts in the pharmaceutical industry to learn more about the demands that future pharmaceutical packaging solutions will have to meet. Thanks to many years of developmental work, SCHOTT now has the technologies and expertise at its research sites in Mainz, Germany, and Duryea, Pennsylvania, U.S.A., to be able to analyze the interactions between coated surfaces and biomolecules. ”We have researchers in the areas of material sciences, molecular biology, protein biochemistry, organic and inorganic chemistry, as well as coating,” says Dr. Robert Hormes, Director of Product Development at SCHOTT forma vitrum. ”The combination of various disciplines is what makes us so unique,” Hormes explains and adds: ”On the one hand, we have valuable know-how in the area of materials, like glass and polymers, but also in the area of glass forming processes, coatings and even biotechnology.”
Based on all of this, SCHOTT offers biopharmaceutical companies screening expertise on the interaction between protein solutions and the various surfaces of primary pharmaceutical packaging. The customer is given the opportunity to have various protein formulation approaches tested using borosilicate glass or polymers, both with and without coatings, to learn which of these would be the ideal material with the least possible tendency to exhibit adsorption. In the meantime, a series of organic molecules have even been identified in Duryea that can be used to coat the surfaces of glass to provide better protection for the highly sensitive proteins against interactions with the surface of packaging. As Dr. Dietrich puts it: ”The results are very encouraging. Initial trials aimed at making this organic coating suitable for mass production are already underway.”
Left: Once the pharmaceutical vials have been washed and dried inside an electric heat tunnel, they are transported to the coating reactor inside a cassette system.
Right: Before they are packaged, the coated vials are subjected to visual quality inspections.
Photos: SCHOTT/T. Hauser
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