Container for an inhalation anesthetic

A pharmaceutical product. The pharmaceutical product includes a container constructed from a material containing polyethylene napthalate. The container defines an interior space. A volume of a fluoroether-containing inhalation anesthetic is contained in the interior space defined by the container.

BACKGROUND OF THE INVENTION 
The present invention relates to a container for an inhalation anesthetic 
and a method for storing an inhalation anesthetic. In particular, the 
present invention is directed to a container constructed from a material 
that provides a barrier to vapor transmission through a wall of the 
container and that is non-reactive with an inhalation anesthetic contained 
therein. 
Fluoroether inhalation anesthetic agents such as sevoflurane 
(fluoromethyl-2,2,2-trifluoro-1-(tri fluoromethyl)ethyl ether), enflurane 
(2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), isoflurane 
(1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), methoxyflurane 
(2,2-dichloro-1,1-difluoroethyl methyl ether) and desflurane 
(2-difluoromethyl 1,2,2,2-tetrafluoroethyl ether) are typically 
distributed in containers constructed of glass. Although these fluoroether 
agents have been shown to be excellent anesthetic agents, it has been 
found that under certain conditions the fluoroether agent and the glass 
container may interact, thereby facilitating degradation of the 
fluoroether agent. This interaction is believed to result from the 
presence of Lewis acids in the glass container material. Lewis acids have 
an empty orbital which can accept an unshared pair of electrons and 
thereby provide a potential site for reaction with the alpha fluoroether 
moiety (--C--O--C--F) of the fluoroether agent. Degradation of these 
fluoroether agents in the presence of a Lewis acid may result in the 
production of degradation products such as hydrofluoric acid. 
The glass material currently used to contain these fluoroether agents is 
referred to as Type III glass. This material contains silicon dioxide, 
calcium hydroxide, sodium hydroxide and aluminum oxide. Type III glass 
provides a barrier to the transmission of vapor through the wall of the 
container, thereby preventing the transmission of the fluoroether agent 
therethrough and preventing the transmission of other vapors into the 
container. However, the aluminum oxide contained in glass materials such 
as type III glass tend to act as Lewis acids when exposed directly to the 
fluoroether agent, thereby facilitating degradation of the fluoroether 
agent. The degradation products produced by this degradation, e.g., 
hydrofluoric acid, may etch the interior surface of the glass container, 
thereby exposing additional quantities of aluminum oxide to the 
fluoroether compound and thereby facilitating further degradation of the 
fluoroether compound. In some cases, the resulting degradation products 
may compromise the structural integrity of the glass container. 
Efforts have been made to inhibit the reactivity of glass to various 
chemicals. For example, it has been found that treating glass with sulfur 
will protect the glass material in some cases. However, it will be 
appreciated that the presence of sulfur on the surface of a glass 
container is not acceptable in many applications. 
Furthermore, glass containers present a breakage concern. For example, 
glass containers may break when dropped or otherwise subjected to a 
sufficient force, either in use or during shipping and handling. Such 
breakage can cause medical and incidental personnel to be exposed to the 
contents of the glass container. In this regard, inhalation anesthetic 
agents evaporate quickly. Thus, if the glass container contains an 
inhalation anesthetic such as sevoflurane, breakage of the container may 
necessitate evacuation of the area immediately surrounding the broken 
container, e.g, an operating room or medical suite. 
Efforts to address breakage concerns typically have involved coating the 
exterior, non-product contact surfaces of the glass with polyvinyl 
chloride (PVC) or synthetic thermoplastic resin such as Surlyn.RTM. (a 
registered trademark of E. I. Du Pont De Nemours and Company). These 
efforts increase the cost of the containers, are not aesthetically 
pleasing, and do not overcome the above-discussed problems related to 
degradation which can occur when using glass to contain 
fluoroether-containing inhalation anesthetic agents. 
For these reasons, it is desirable to provide a container constructed from 
a material other than glass in order to store, transport, and dispense 
inhalation anesthetics, thereby avoiding the above-discussed shortcomings 
of glass. The preferred material does not contain Lewis acids which can 
promote the degradation of the inhalation anesthetic agent, provides a 
sufficient barrier to vapor transmission into and out of the container, 
and increases the container's resistance to breakage relative to a glass 
container. 
SUMMARY OF THE INVENTION 
The present invention is directed to a pharmaceutical product. The product 
includes a container constructed from a material containing polyethylene 
napthalate. The container defines an interior space in which a volume of a 
fluoroether-containing inhalation anesthetic is contained. 
In an alternative embodiment, the present invention is directed to a 
pharmaceutical product in which a container defining an interior space has 
an interior surface adjacent to the interior space. The interior surface 
of the container is constructed from a material containing polyethylene 
napthalate. A volume of a fluoroether-containing inhalation anesthetic is 
contained in the interior space of the container. 
The present invention is further directed to a method for storing an 
inhalation anesthetic. The method includes the step of providing a 
predetermined volume of a fluoroether-containing inhalation anesthetic. A 
container also is provided, the container being constructed from a 
material containing polyethylene napthalate. The container defines an 
interior space. The predetermined volume of fluoroether-containing 
inhalation anesthetic is placed in the interior space of the container. 
In an alternative embodiment of the method of the present invention, a 
predetermined volume of a fluoroether-containing inhalation anesthetic is 
provided. In addition, a container having an interior surface defining an 
interior space is provided. The interior surface of the container is 
constructed from a material containing polyethylene napthalate. The 
predetermined volume of a fluoroether-containing inhalation anesthetic is 
placed in the interior space of the container.

DETAILED DESCRIPTION 
A pharmaceutical product constructed in accordance with the present 
invention is generally indicated at 10 of FIG. 1. Pharmaceutical product 
10 includes container 12 having an interior surface 14. Interior surface 
14 defines an interior space 16 within container 12. An inhalation 
anesthetic 18 is contained within interior space 16 of container 12. In a 
preferred embodiment of the present invention, inhalation anesthetic 18 
contains a fluoroether compound. Fluoroether-containing inhalation 
anesthetics useful in connection with the present invention include, but 
are not necessarily limited to, sevoflurane, enflurane, isoflurane, 
methoxyflurane, and desflurane. Inhalation anesthetic 18 is a fluid, and 
may include a liquid phase, a vapor phases, or both liquid and vapor 
phases. FIG. 1 depicts inhalation anesthetic 18 in a liquid phase. 
The purpose of container 12 is to contain inhalation anesthetic 18. In the 
embodiment of the present invention depicted in FIG. 1, container 12 is in 
the shape of a bottle. However, it will be appreciated that container 12 
can have a variety of configurations and volumes without departing from 
the spirit and scope of the present invention. For example, container 12 
can be configured as a shipping vessel for large volumes (e.g., tens or 
hundreds of liters) of inhalation anesthetic 18. Such shipping vessels can 
be rectangular, spherical, or oblong in cross-section without departing 
from the intended scope of the invention. 
Container 12 preferably is constructed of a material that minimizes the 
amount of vapor transmission into and out of container 12, thereby 
minimizing the amount of inhalation anesthetic 18 that is released from 
interior space 16 of container 12 and thereby minimizing the amount of 
vapor transmission, e.g., water vapor transmission, from an external 
environment of container 12 into interior space 16 and thus into 
inhalation anesthetic 18. Container 12 also is preferably constructed of a 
material that does not facilitate degradation of inhalation anesthetic 18. 
In addition, container 12 preferably is constructed of a material that 
minimizes the potential for breakage of container 12 during storage, 
shipping, and use. 
It has been found that containers constructed from a material that contains 
polyethylene napthalate provide the desired vapor barrier, chemical 
interaction, and strength characteristics when used with inhalation 
anesthetics 18. One of ordinary skill will appreciate that there are many 
different types of polyethylene napthalate polymers which vary in their 
molecular weight, additives, and napthalate content. These polymers can be 
categorized into three distinct groups; namely, homopolymers, copolymers 
and blends. It has been found that polyethylene napthalate homopolymers 
provide higher barriers to vapor transmission when compared to copolymers 
and blends. For this reason, it is preferable that the material from which 
container 12 of the present invention is constructed contains a 
polyethylene napthalate homopolymer. However, it will be appreciated that 
certain copolymers and blends of polyethylene napthalate can be used in 
connection with the present invention, provided they provide an adequate 
barrier to the transmission of vapors, e.g., inhalation anesthetic and 
water vapors, therethrough, and provided that they provide the desired 
strength and non-reactivity to inhalation anesthetic 18. 
In addition to the desirable vapor barrier characteristics of materials 
containing polyethylene napthalate, polyethylene napthalate does not 
contain Lewis acids and therefore does not pose any threat of facilitating 
the degradation of a fluoroether-containing inhalation anesthetic 
contained in a container constructed therefrom. 
An example of a polyethylene napthalate material useful in connection with 
the present invention is HiPERTUF.TM. 90000 polyester resin (trademark of 
Shell Chemical Company), a 2,6 dimethyl napthalate based polyethylene 
napthalate. One of ordinary skill will appreciate that other polyethylene 
napthalates can be used without departing from the scope of the invention 
set forth in the appended claims. 
In a first embodiment of the present invention, container 12 is constructed 
of a single layer of material. That is, container 12 is substantially 
homogenous throughout its thickness. In this embodiment, as 
above-discussed, container 12 is constructed of a material that contains 
polyethylene napthalate. 
In an alternative embodiment of the present invention, container 12 is 
multi-laminar. As used herein, the term multi-laminar is intended to 
include (i) materials constructed of more than one lamina where at least 
two of the lamina are constructed of different materials, i.e., materials 
that are chemically or structurally different, or materials that have 
different performance characteristics, wherein the lamina are bonded to 
one another or otherwise aligned with one another so as to form a single 
sheet; (ii) materials having a coating of a different material; (iii) 
materials having a liner associated therewith, the liner being constructed 
of a different material; and (iv) known variations of any of the above. In 
this alternative embodiment of the present invention, interior surface 14 
of container 12 is preferably constructed of a material containing 
polyethylene napthalate. It will be appreciated that the surface of 
container 14 in contact with a fluoroether-containing inhalation 
anesthetic contained therein will preferably contain polyethylene 
napthalate in order to provide the desired vapor barrier characteristics 
and simultaneously minimize the likelihood of degradation of the 
fluoroether-containing inhalation anesthetic. 
In an alternative embodiment of the present invention, container 12 is 
constructed of a material containing polymethylpentene. In a preferred 
embodiment, a polycyclomethylpentene is used. An example of a 
polymethylpentene material useful in connection with the present invention 
is "Daikyo Resin CZ" which is manufactured and distributed by the 
Daikyo/Pharma-Gummi/West Group. This is a polycyclomethylpentene material. 
In another alternative embodiment of the present invention, interior 
surface 14 of container 12 is constructed of a material containing 
polymethylpentene. 
As depicted in FIG. 1, container 12 defines an opening 20. Opening 20 
facilitates the filling of container 12 and provides access to the 
contents of container 12, thereby allowing the contents to be removed from 
container 12 when they are needed. In the embodiment of the present 
invention depicted in FIG. 1, opening 20 is a mouth of a bottle. However, 
it will be appreciated that opening 20 can have a variety of known 
configurations without departing from the scope of the present invention. 
Cap 22 is constructed to seal fluidly opening 20, thereby fluidly sealing 
inhalation anesthetic 16 within container 12. Cap 22 can be constructed of 
a variety of known materials. However, it is preferable that cap 22 be 
constructed of a material that minimizes the transmission of vapor 
therethrough and that minimizes the likelihood of degradation of 
inhalation anesthetic 16. In a preferred embodiment of the present 
invention, cap 22 is constructed from a material containing polyethylene 
napthalate. In an alternative embodiment of the present invention, cap 22 
has an interior surface 24 that is constructed from a material containing 
polyethylene napthalate. In another alternative embodiment of the present 
invention, cap 22, and/or interior surface 24 thereof, is constructed of a 
material containing polyethylene, the material having vapor barrier 
characteristics sufficient to minimize the transmission of water vapor and 
inhalation anesthetic vapor therethrough. In still another alternative 
embodiment of the present invention, cap 22, and/or interior surface 24 
thereof, is constructed of a material containing polymethylpentene. 
Cap 22 and container 12 can be constructed such that cap 22 can be 
threadingly secured thereto. Containers and caps of this type are well 
known. Alternative embodiments of cap 22 and container 12 are also 
possible and will be immediately recognized by those of ordinary skill in 
the relevant art. Such alternative embodiments include, but are not 
necessarily limited to, caps that can be "snap-fit" on containers, caps 
that can be adhesively secured to containers, and caps that can be secured 
to containers using known mechanical devices, e.g., a ferrule. In the 
preferred embodiment of the present invention, cap 22 and container 12 are 
configured such that cap 22 can be removed from container 12 without 
causing permanent damage to either cap 22 or container 12, thereby 
allowing a user to reseal opening 20 with cap 22 after the desired volume 
of inhalation anesthetic 18 has been removed form container 12. 
Container 12 may include additional features that form no part of the 
present invention. For example, container 12 can be configured to include 
a system for dispensing inhalation anesthetic 18 from container 12 into an 
anesthesia vaporizer. U.S. Pat. No. 5,505,236 to Grabenkort discloses such 
a system. 
Methods for making containers of the type used in the present invention are 
known in the art. For example, it is known that polyethylene napthalate 
must be dried to a moisture level of approximately 0.005% prior to 
processing in order to yield the optimal physical properties in container 
12 and cap 22. A preferred method for making containers 12 and caps 22 
useful in connection with the present invention entails the 
injection-stretch-blow molding of a material containing polyethylene 
napthalate. Machines manufactured by AOKI Technical Laboratory, Inc. of 
Tokyo, Japan are particularly useful in performing this molding operation. 
The polyethylene napthalate-containing material is injection molded into a 
preform which is then transferred to a blow station where it is stretched 
and blown to form the container. The container is then batch heated and 
annealed in a convective oven. 
It has been found that annealing of a material containing polyethylene 
napthalate increases the degree of crystallization in the material to a 
level not attainable using a blow molding process alone. Increased 
crystallization results in a higher barrier to vapor transmission, thereby 
enhancing the vapor barrier performance characteristics of a container 12 
constructed of an annealed material containing polyethylene napthalate. 
Increased crystallization also reduces the overall weight of container 12 
(based upon the weight required to attain a selected container strength) 
and the amount of material required to achieve a given container strength 
for container 12. Increased container strength allows a container to 
withstand greater loads during shipping, storage, and use, thereby 
minimizing breakage of the container. For example, greater container 
strength is desirable when containers 12 are placed one on top of another, 
as can occur when containers 12, or cartons or pallets of containers 12, 
are stacked for shipping or storage. It should be noted that a container 
constructed of a material containing an annealed polyethylene napthalate 
weighs less than a glass container having comparable strength 
characteristics, is less susceptible to breakage than a glass container of 
comparable weight, and costs less to manufacture than a glass container of 
comparable performance characteristics. A lower container weight also 
reduces the costs associated with shipping such containers. Further, such 
a container does not present the potential for degradation of a 
fluoroether-containing inhalation anesthetic that is present with a glass 
container. 
The method of the present invention includes the step of providing a 
predetermined volume of a fluoroether-containing inhalation anesthetic 16. 
The fluoroether-containing inhalation anesthetic 16 can be one or more of 
sevoflurane, enflurane, isoflurane, methoxyflurane, and desflurane. A 
container 12 constructed in accordance with the above-described 
pharmaceutical product also is provided. In particular, container 12 
defines an interior space and is constructed of a material containing 
polyethylene napthalate. The method of the present invention further 
includes the step of placing the predetermined volume of 
fluoroether-containing inhalation anesthetic 16 into the interior space 
defined by the container. 
In an alternative embodiment of the method of the present invention, a 
predetermined volume of a fluoroether-containing inhalation anesthetic 16 
is provided. The fluoroether-containing inhalation anesthetic 16 can be 
one or more of sevoflurane, enflurane, isoflurane, methoxyflurane, and 
desflurane. A container 12 constructed in accordance with the 
above-described product also is provided. In particular, container 12 has 
an interior surface 14 which defines an interior space 16. Interior 
surface 14 of container 12 is constructed of a material containing 
polyethylene napthalate. The method further includes the step of placing 
the predetermined volume of fluoroether-containing inhalation anesthetic 
into the interior space defined by the container. 
In another alternative embodiment of the method of the present invention, a 
predetermined volume of a fluoroether-containing inhalation anesthetic 16 
is provided. The fluoroether-containing inhalation anesthetic 16 can be 
one or more of sevoflurane, enflurane, isoflurane, methoxyflurane, and 
desflurane. A container 12 constructed in accordance with the 
above-described product also is provided. In particular, container 12 
defines an interior space and is constructed of a material containing 
polymethylpentene. The method further includes the step of placing the 
predetermined volume of a fluoroether-containing inhalation anesthetic 16 
into the interior space defined by the container. 
In yet another alternative embodiment of the method of the present 
invention, a predetermined volume of a fluoroether-containing inhalation 
anesthetic 16 is provided. The fluoroether-containing inhalation 
anesthetic 16 can be one or more of sevoflurane, enflurane, isoflurane, 
methoxyflurane, and desflurane. A container 12 constructed in accordance 
with the above-described product also is provided. In particular, 
container 12 has an interior surface 14 which defines an interior space 
16. Interior surface 14 of container 12 is constructed of a material 
containing polymethylpentene. The method further includes the step of 
placing the predetermined volume of fluoroether-containing inhalation 
anesthetic into the interior space defined by the container. 
In each of the embodiments of the method of the present invention, 
container 12 can define an opening 20 therein whereby opening 20 provides 
fluid communication between interior space 16 of container 12 and an 
external environment of container 12. Each of the embodiments of the 
present invention may further include the step of providing a cap 22 
constructed of a material containing polyethylene, polyethylene 
napthalate, and polymethylpentene. In the alternative, cap 22 can be 
constructed such that an interior surface 24 thereof is constructed of a 
material containing polyethylene, polyethylene napthalate, and 
polymethylpentene. The method of the present invention further includes 
the step of sealing the opening defined by container 12 with cap 22. 
Although the pharmaceutical product and the method of the present invention 
have been described herein with respect to certain preferred embodiments, 
it will be apparent to one of ordinary skill in the art that various 
modifications can be made to the invention without departing from the 
spirit and scope of the invention disclosed herein as claimed in the 
appended claims.