EP-4741655-A2 - ATOMIC LAYER DEPOSITION COATED PHARMACEUTICAL PACKAGING AND IMPROVED SYRINGES AND VIALS, E.G. FOR LYOPHILIZED/COLD-CHAIN DRUGS/VACCINES

Abstract

The present disclosure is directed to pharmaceutical packaging such as syringes, vials, and blood tubes having a thermoplastic wall that is coated with a gas barrier coating in which at least one layer is applied by atomic layer deposition. The gas barrier coating may include, for example, one or more layers of SiO 2 , one or more layers of Al2O3, or a combination thereof, and may serve as a barrier against a variety of gases including oxygen, water vapor, and nitrogen. The present disclosure is also directed to syringes and vials which are configured for the storage of lyophilized or cold-chain drugs and in particular to maintain container closure integrity throughout the supply and storage conditions associated with such drugs. The present disclosure is also directed to evacuated blood tubes having extended shelf lives.

Inventors

• TAHA, Ahmad
• ABRAMS, ROBERT S.
• BREELAND, Adam
• FERRER, JAVIER

Assignees

• SiO2 Medical Products, Inc.

Dates

Publication Date

20260513

Application Date

20210622

Claims (15)

1. An evacuated blood tube comprising: • a vessel comprising a lumen defined at least in part by a thermoplastic side wall, the thermoplastic side wall having an interior surface facing the lumen and an outer surface, and a top defining an opening to the lumen; • a gas barrier coating supported by at least one of the interior surface and the outer surface of the side wall, the gas barrier coating comprising: ∘ an oxygen barrier coating or layer, the oxygen barrier coating or layer being effective to provide the evacuated blood tube with an oxygen transmission rate constant less than 0.0010 d -1 ; and ∘ a water vapor barrier coating or layer, the water vapor barrier coating or layer being effective to reduce the ingress of water vapor into the lumen to 0.1 mg/package/day or less, when stored at 40 °C and 75% relative humidity; and • a stopper seated within the opening and sealing the lumen; wherein at least one of the oxygen barrier coating or layer and the water vapor barrier coating or layer consists of a plurality of atomic monolayers of a pure element or compound.
2. The evacuated blood tube of claim 1, in which the oxygen barrier coating or layer is effective to provide the evacuated blood tube with an oxygen transmission rate constant less than 0.0003 d -1 .
3. The evacuated blood tube of any preceding claim, wherein the oxygen barrier coating or layer comprises or consists of SiO 2 .
4. The evacuated blood tube of any preceding claim, in which the gas barrier coating reduces the ingress of water vapor into the lumen to less than 0.08 mg/package/day, when stored at 40 °C and 75% relative humidity.
5. The evacuated blood tube of any preceding claim, wherein the water vapor barrier coating or layer comprises or consists of Al 2 O 3 .
6. The evacuated blood tube of any preceding claim, wherein each of the oxygen barrier coating or layer and the water vapor barrier coating or layer consists of a plurality of atomic monolayers of a pure element or compound
7. The evacuated blood tube of any preceding claim, in which the thermoplastic side wall consists predominantly of a commodity resin selected from the following: PET, PETG, polypropylene, a polyamide, polystyrene, polycarbonate, TRITAN ™ , a cyclic block copolymer (CBC) resin, or a thermoplastic olefinic polymer, or any combination thereof.
8. The evacuated blood tube of any one of claims 1 to 6, wherein the thermoplastic side wall consists predominantly of COP or COC.
9. The evacuated blood tube of any preceding claim, in which the gas barrier coating is effective to extend the shelf life of the evacuated blood tube to at least 28 months, the shelf life defined by the amount of time after evacuation the tube maintains a draw volume capacity of at least 90% of the draw volume capacity of a newly evacuated vessel of the same kind.
10. The evacuated blood tube of any preceding claim, further comprising a blood preservative within the lumen.
11. The evacuated blood tube of claim 10, in which the gas barrier coating is effective to reduce the amount of solvent loss of the blood preservative over a shelf life of the blood tube.
12. The evacuated blood tube of any preceding claim, wherein the gas barrier coating is supported by the interior surface of the wall.
13. The evacuated blood tube of claim 12, further comprising a pH protective coating between the lumen and the gas barrier coating.
14. The evacuated blood tube of claim 13, wherein the pH protective coating or layer comprises SiO x C y or SiN x C y , wherein x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3.
15. The evacuated blood tube of any one of claims 13 to 14, wherein the pH protective coating or layer is deposited by PECVD.

Description

This application claims priority to U.S. Provisional Patent Application No. 63/042,545, filed on June 22, 2020; U.S. Provisional Patent Application No. 63/080,675, filed on September 18, 2020; U.S. Provisional Patent Application No. 63/109,232, filed on November 3, 2020; U.S. Provisional Patent Application No. 63/113,808, filed on November 13, 2020; and U.S. Provisional Patent Application No. 63/168,580, filed on March 31, 2021; the entireties of which are incorporated by reference herein. FIELD OF THE INVENTION The present invention relates to the technical field of barrier coated surfaces, for example interior surfaces of pharmaceutical packages or other vessels for storing or other contact with fluids. Examples of suitable fluids include foods, nutritional supplements, drugs, inhalation anaesthetics, diagnostic test materials, biologically active compounds, or body fluids, for example blood. The present invention also relates to a pharmaceutical package or other vessel and to a method for making a pharmaceutical package with a pH protective coating or layer between the contents and the barrier coating or layer. The present invention also relates more generally to medical articles, including articles other than packages or vessels, for example catheters. The present disclosure also relates to improved methods for processing pharmaceutical packages or other vessels, for example multiple identical pharmaceutical packages or other vessels used for pharmaceutical preparation storage and delivery, venipuncture and other medical sample collection, and other purposes. The resulting packages are also claimed. Such pharmaceutical packages or other vessels are used in large numbers for these purposes, and must be relatively economical to manufacture and yet highly reliable in storage and use. BACKGROUND OF THE INVENTION One important consideration in manufacturing pharmaceutical packages or other vessels for storing or other contact with fluids, for example vials and pre-filled syringes, is that the contents of the pharmaceutical package or other vessel desirably will have a substantial shelf life. During this shelf life, it is important to isolate the material filling the pharmaceutical package or other vessel from the vessel wall containing it, or from barrier layers or other functional layers applied to the pharmaceutical package or other vessel wall to avoid leaching material from the pharmaceutical package or other vessel wall, barrier layer, or other functional layers into the prefilled contents or vice versa. The traditional glass pharmaceutical packages or other vessels are prone to breakage or degradation during manufacture, filling operations, shipping, and use, which means that glass particulates may enter the drug. The presence of glass particles has led to many FDA Warning Letters and to product recalls. As a result, some companies have turned to plastic pharmaceutical packages or other vessels, which provide greater dimensional tolerance and less breakage than glass, but its use for primary pharmaceutical packaging remains limited due to its gas permeability: Plastic allows small molecule gases such as oxygen to permeate into (or out of) the article. In addition to oxygen, many plastic materials also allow moisture, i.e. water vapor, to permeate into (or out of) the article. The permeability of plastics to gases, such as oxygen and water vapor, is significantly greater than that of glass and, in many cases (as with oxygen-sensitive drugs such as epinephrine), plastics have been unacceptable for that reason. The problem of gas permeability has been addressed by using specialty resins (for example Cyclic Olefin Polymer ("COP") or Cyclic Olefin Copolymer ("COC")) and by adding an oxygen barrier coating or layer to the plastic pharmaceutical package where it contacts fluid contents of the package. One such oxygen barrier layer is a very thin coating of SiOx, as defined below, applied by plasma enhanced chemical vapor deposition. The COP and COC specialty resins have been utilized due to their water vapor barrier properties. This is because, in contrast to oxygen barrier properties which can be provided by the PECVD of a thin coating of SiOx, it is not known how to apply a suitable, e.g. thin yet effective and safe for use in a pharmaceutical package, water vapor barrier coating by PECVD. The inability to provide a suitable water vapor barrier coating by PECVD has necessitated the use of specialty resins such as COP and COC. It has been shown that vessels made from specialty resins such as COP and COC may be provided with adequate properties for some applications. The properties include gas barrier properties that are protected from dissolution by the aqueous contents of the package, water vapor barrier properties (which are a property of the COP and COC resins), low levels of organic and inorganic extractables, and low levels of visible and subvisible particles (meeting the requirements of USP 789 - ophth