Patent Application
20120152791
The present disclosure relates to methods of packaging oxygen sensitive products in containers pre-filled with an inert atmosphere.
Liquid nitrogen is known for use in pressurizing containers in the beverage industry and other consumer products. U.S. Pat. No. 6,182,715 describes an apparatus and method for pressurizing containers using liquid nitrogen. These pressurization techniques are not related to nor do they accomplish meaningful levels of de-oxygenation of containers.
Removal of oxygen and/or moisture from the interior of a container prior to filling with a product can be critical to the stability and shelf life of products. Highly oxygen and/or water sensitive products should be placed into containers that are substantially free of oxygen and/or water.
Previous applications of liquid nitrogen as a container de-oxygenation agent are exemplified by U.S. Pat. No. 6,105,341 to Campbell. As discussed by Campbell, “[t]he conventional liquid nitrogen injection process suffers from many problems. One problem is that it is difficult to properly time the process so that at the exact time when the lid is seamed to the container body, (1) substantially all of the air has been displaced so that the sealed container has less than about 2% oxygen, (2) all of the liquid nitrogen has vaporized, and (3) no surrounding air has flowed back into the container body.” The Campbell process is defined by claim 1 of the Campbell patent as the sequential steps of:
(a) filling a succession of container bodies with goods;
(b) injecting the succession of container bodies with a predetermined amount of liquid nitrogen;
(c) covering the open tops of the container bodies with lids; and
(d) applying a biasing force against the lids to maintain the lids on the liquid nitrogen filled container bodies until the container bodies reach the seaming mechanism, the biasing force being sufficient to allow (i) a portion of nitrogen gas from vaporization of the liquid nitrogen, and (ii) air originally present in the container body, to escape from the container body, while preventing surrounding air from entering the container body.
This approach has deficiencies that are particularly relevant to Highly oxygen and/or water sensitive products. First, liquid nitrogen injection occurs after product filling. As can be seen in Campbell
For highly sensitive products, industrial practices packaging processes have been developed to cope with oxygen sensitivity pharmaceuticals in particular.
The product to be contained is normally pyrogenated (sterilized) and deoxygenated using nitrogen sparging. The container in which the product is to be filled is autoclaved and dried.
The container is purged with gaseous nitrogen. Because nitrogen has the similar properties as air (density in particular), a large quantity of nitrogen is required to displace air to the necessary oxygen levels. Finally product loading into the container is performed as quickly as possible. A common sequence in the art is:
As illustrated by the above, the prior art processes for packaging highly sensitive products suffer from a number of undesirable features including:
The present invention in comparison:
The invention is described in part by the following numbered sentences:
1. A process for the removal of an atmosphere within a container cavity comprising the steps of:
“Highly sensitive products” are defined as products that suffer from a shortened shelf life (e.g. chemical stability) or are physically changed (e.g. hygroscopic moisture absorption by a powder) to render the product unsuitable for human or animal use when exposed to the atmosphere as compared to when the products are maintained in a substantially pure (e.g. 99.9%) inert gas atmosphere of nitrogen.
“Highly oxygen sensitive products” are defined as products with a shortened shelf life if exposed to greater than 1.5% oxygen. Some highly oxygen sensitive products require 1% or less oxygen for stability.
“Highly water sensitive products” are defined as products that react with moisture to change in chemical makeup or physical properties, thereby rendering the product unsuitable for human or animal use. An example is a highly hygroscopic powder agglomerating due to moisture absorption. Highly water sensitive products should be stored in atmospheres having as little moisture as possible such as a relative humidity of 40% or less, 20% or less or even 10% or less, depending on the specific moisture uptake rate and anticipated product storage period.
“Liquid nitrogen intolerant products” are defined as products that are altered in chemical makeup or physical properties by direct contact with liquid nitrogen. In some cases this alteration renders the product unsuitable for human or animal consumption and/or reduces the effectiveness of the product for the product's intended use. For example, a liquid nitrogen intolerant antibiotic may be reduced in potency by exposure to liquid nitrogen rendering the normal dose of antibiotic insufficient to treat an indicated infection.
The invention generally relates to the use of liquid nitrogen to displace air, or other water and/or oxygen containing atmospheres, from containers prior to filling with a highly sensitive product. The process in general has two steps: a) depositing a volume of liquid nitrogen into the cavity of an empty container and b) applying a vacuum to the cavity of the container. The vacuum will accelerate vaporization and thereby shorten the liquid nitrogen vaporization time frame. This procedure results in a highly effective one step de-oxygenation and/or de-humidification of the container cavity. Further, the evacuation ensures complete liquid nitrogen vaporization prior to product filling.
In general, the container will be sterilized (autoclave and dried, gamma irradiated, etc.). Liquid nitrogen expands approximately 700 times upon vaporization. Thus a small volume of liquid nitrogen placed at the bottom of a container cavity will expand into a gas and push out the pre-existing container atmosphere. A liquid nitrogen dispensing apparatus will generally be positioned in close proximity to the product filling point, the closer the better. The container having the liquid nitrogen is generally exposed to a vacuum sufficient to accelerate the liquid nitrogen's vaporization. Accelerating the liquid nitrogen vaporization increases the efficiency of the removal of the pre-existing atmosphere. The evacuation and liquid nitrogen deposition steps may be concurrent or in either order (deposition-evacuation or evacuation-deposition) as long as the liquid nitrogen experiences the vacuum sufficiently to shorten the time required for complete liquid nitrogen vaporization. Optionally, additional volumes of liquid nitrogen may be deposited into the cavity of the container either while the container is being evacuated or by alternating between separate liquid nitrogen deposition and evacuation steps. Product may then be dispensed into the container, generally under controlled atmosphere conditions such as a nitrogen atmosphere as is known and practiced in the art. After product filling, an additional volume of liquid nitrogen may optionally be added prior to sealing closed the container to a) flush out the headspace above the product and/or b) pressurize the container.
In general the ratio of the Volume of the Container/Volume of Liquid Nitrogen will be 730 or more. For example, 3 to 4 ml of Liquid Nitrogen may be used to completely evacuate a 5″ diameter×9″ tall container. The volume of liquid nitrogen is in part dependent on the distance between or time between liquid nitrogen addition and evacuation. More Liquide nitrogen may be added to compensate for extended travel times to the evacuation position to ensure sufficient liquid nitrogen is present for the evacuation step.
The speed of the container movement on a production line will dictate the location of the liquid nitrogen addition on the production line to ensure total vaporization of the liquid nitrogen prior to product filling but minimize the time between full vaporization and product filling. The evacuation step ensures complete vaporization and allows one to shorten the time for evaporation. The shorter the time/distance between evacuation and product filling, the better.
Product oxygen content is important as product derived oxygen affects the final oxygen content in the container. Hence recommend that the product is sparged properly with Nitrogen prior to filling in the container.
The travel between a container filling station and the sealing station should be as short as possible. For long travel the production line should be enclosed with a nitrogen blanket, e.g., under a hood providing a positive pressure of Nitrogen gas.
The process described herein is suitable for use in the manufacture and packaging of oxygen sensitive products such as certain pharmaceuticals.
