By Juan Gudino, Medical Market Manager, Specialty Coating Systems
New and sophisticated drugs require packaging protection as well as innovative devices to ensure their accurate and safe deployment into the human body. In this regard, manufacturers of pharmaceutical containers and prefilled syringes often face several challenges, including sticking components, unwanted materials leaching from the container into the drug, aggressive drugs that damage their container, etc. One example of these challenges can be seen with prefilled syringes in storage. In some cases, the rubber used for syringe plungers may contain unwanted trace elements that can leach or be extracted from the stopper, contaminating the contents of the syringe and thus compromising the effectiveness of the medication and/or patient safety. Also, a phenomenon often referred to as “stiction” can occur, where the plunger doesn’t slide freely upon first push. Using a larger-than-desired force to break the plunger free can create an initial uneven delivery of the drug.
|Parylene coatings can be employed to preserve plunger functionality.|
Vials, bottles, tubes, and pouches also face challenges. Many of these containers must control more-aggressive drugs and increasingly delicate powder formulations and capsules that require long shelf life properties. In some cases, the glass or plastic packaging material may have an undesirable trace element in it, an element that could leach into the drug, causing
Manufacturers looking to resolve these types of challenges are finding a new solution in parylene conformal coatings, which provide both a protective barrier and lubricant for pharmaceutical applications, without adding physical dimension. Parylene conformal coatings are biocompatible, biostable and offer excellent barrier properties. They also provide dry film lubricity—better than some PTFEs. Most conformal coating materials used in other industries simply cannot provide the same protection in as thin a coating as parylene.
Parylene is the generic name for a unique series of chemically inert, polymeric organic coatings. Several types of parylene exist to suit a variety of applications. All are free of fillers, stabilizers, solvents, catalysts, and plasticizers. As a result, the parylenes present no leaching, outgassing, or extraction issues.
Devices to be coated with parylene are placed in a room-temperature deposition chamber. A powdered raw material, known as “dimer,” is placed in the vaporizer at the opposite end of the coating system. The double-molecule dimer is heated, sublimating it directly to a vapor, and the vapor is then heated to a very high temperature that cracks (pyrolizes) it into a monomeric vapor. This vapor then flows into an ambient temperature deposition chamber where it spontaneously polymerizes onto all surfaces, forming the ultra-thin, uniform and extremely conformal parylene film. The entire parylene coating process is carried out in a closed system under a controlled vacuum. The deposition chamber and items to be coated remain at room temperature throughout the process and no additional cure process or steps are required. The molecular “growth” of parylene coatings ensures not only a uniform, conformal coating at the thickness specified by the manufacturer, but because parylene is formed from a gas, it penetrates into every crevice, regardless of how seemingly inaccessible. This ensures complete encapsulation of the substrate without blocking or bridging even the smallest openings.
There are three commonly utilized variants of parylene: N and C and Parylene HT. Each parylene has unique properties that suit it to specific medical coating applications. Parylene N has particularly high dielectric strength and a dielectric constant that is independent of frequency. Because of its high molecular activity in the monomer vapor state, parylene N has a greater penetrating power than parylene C, with the ability to coat into deep recesses and blind holes. However, because of its lower maximum operating temperature, it is not suitable for applications requiring steam sterilization.
Parylene C has a chlorine atom in its molecular structure, resulting in modified electrical and physical properties, particularly its low permeability to moisture and corrosive gases. Because of its excellent barrier properties, parylene C is often the first choice for protection of pharmaceutical containers, syringes, and vials.
Parylene HT substitutes fluorine for the hydrogen atoms in the parylene N molecule, resulting in some very useful attributes. Parylene HT is the most stable parylene in the presence of ultraviolet light and is thermally stable at high temperatures (350°C short-term, 450°C long-term). It also has the best crevice penetrating capability.
Parylenes C and N and Parylene HT offer similar lubricity capabilities and all are biocompatible. Since syringes and pharmaceutical containers are typically manufactured in mass quantity, the manufacturer can have components coated before sending them to the end customer, who then fills and packages them for distribution.
Prefilled Syringes: parylene coatings can play a variety of roles in solving challenges that prefilled syringe manufacturers face. To begin, parylene increases lubricity and eliminates stiction issues, preventing extractables and leachables and/or to avoid cold-welding of components parts after several months of storage.
Since parylenes exhibit low coefficients of friction, prefilled syringe manufacturers may benefit from coating the plunger, barrel, needle, or even elastomeric cannulas with parylene to achieve improved gliding movement of its components, resulting in controlled doses to patients.
|Devices to be coated with Parylene are placed in a room-temperature deposition chamber.|
In long-term applications, FDA has found evidence of vulcanizing agents that leached from the uncoated rubber stopper during storage. Parylene coated parts can prevent such leaching and compatibility issues between the drug product and the materials used. Since parylene is applied as a vapor and encapsulates the substrate, nothing leaches from the substrate and the drug does not penetrate into the substrate.
Finally, prefilled syringes are designed to minimize dead space. Manufacturers try to reduce this dead space to zero by using flexible elastomeric components in the device, but when these eliminators are clamped against themselves for extended periods of time, some elastomers will “cold flow” or weld themselves together. This can be problematic when the material, which is intended to keep the medication clean, sterile, and safe, is bonded to itself and won’t open. A thin coating of parylene on these elastomers can prevent such cold flow welding.
Vials and containers: There are several factors to consider when designing pharmaceutical packaging: the selection of a material, the packaging/material interaction with the drugs, manufacturing (filling, assembling, sterilization), the function of packaging (containment, protection, dose dispensing), and the already mentioned stability during storage.
Under Pharmacopeia, FDA, and ISO testing, it is recommended that containers and closures for human use be analyzed for extractable compounds. There must be no toxic interaction between drug product and container. Risk of interaction may occur when there is permanent contact between a drug and components, including needle glue, the needle itself, traces of metal used for glass syringe production, different elastomer formulations (plunger and tip cover), etc. Utilizing a conformal coating will prevent such interaction between the packaging materials and drugs, acting as a physical barrier.
Some pharmaceutical packages use sealing mechanisms to ensure needle sterility and prevent premature drug dispensing. Such a seal can occasionally form a very tight bond as it sits against itself, making the seal difficult to break. Coating these components with parylene before assembly can help prevent seal bonding. In this case, parylene actually acts as a release agent, allowing the sealing material to release easily when needed.
Pharmaceutical containers that are not intended to be opened utilize a syringe needle to withdraw drug from the vial. In these cases, a needle pierces the top of the vial and the drug is withdrawn into the syringe. The caps on these containers have a septum, or a membrane, of a polymeric or elastomeric material that is penetrated by a needle. These membranes can be quite tacky, preventing the needle from sliding through as easily as desired. Coating the septum with a thin layer of parylene alleviates this problem.
Depending on the different routes of administration (oral, topical, transmucosal, etc.), the packaging design presents different challenges for pharmaceutical containers. In addition to liquid, powder, and tablet pharmaceutical contents, containers with on-board propellants become inhalers, which are designed to dispense precise doses. Other containers might hold contents that are sensitive to air, such as oral dissolve strips or medicated swabs. Some of these applications, e.g., fine powders and coated swabs, are extremely susceptible to sub-micron levels of moisture and behave as sponges, actually pulling moisture from container materials. This moisture can contaminate drugs, shortening their shelf life or, worse, causing a safety issue for patients. The inertness and chemical barrier properties inherent to parylene coatings can significantly reduce the risk of such compromised medications.
In conclusion, parylene provides excellent bidirectional fluid/moisture barrier properties, preventing the leaching of packaging elements into the pharmaceutical while simultaneously preventing the pharmaceutical from damaging the packaging materials. Parylene is also highly lubricious, enhancing surface-to-surface sliding action as well as preventing cold flow welding. Parylenes N and C and Parylene HT are certified biocompatible via an extensive series of ISO 10993 biological evaluations as well as USP Class VI certifications, and do not lose any of their properties when subjected to various forms of sterilization (steam, gamma and e-beam irradiation, EtO and H₂O₂ plasma). Finally, all of these properties of parylene are available to pharmaceutical packaging manufacturers in an ultra-thin coating, one that rarely exceeds 25 micron in thickness.
Gudino can be reached at email@example.com.