FORMULATION AQUEUSE D'ACYCLOVIR ET PROCEDE DE STOCKAGE ASSOCIE

AQUEOUS ACYCLOVIR FORMULATION AND METHOD FOR STORING SAME

Abrégé français

Procédé permettant de stocker une solution contenant de l'acyclovir et produit pharmaceutique contenant une solution d'acyclovir. Le procédé fait appel à un volume prédéterminé d'une solution d'acyclovir convenant pour l'administration parentérale à un patient, et à un récipient conçu pour contenir ledit volume prédéterminé. Le récipient est fabriqué dans un matériau renfermant du polyméthylpentène et définit un orifice. La solution d'acyclovir est placée dans le récipient. Le procédé fait ensuite appel à un bouchon configuré de façon à permettre la fermeture fluidique hermétique de l'orifice défini par le récipient, qui est ensuite fermé à l'aide du bouchon. Le produit pharmaceutique comprend une solution d'acyclovir contenue dans un récipient fabriqué dans un matériau renfermant du polyméthylpentène. Le récipient définit un orifice. Le produit comprend en outre un bouchon, revêtu d'une résine fluorée, qui permet la fermeture fluidique hermétique de l'orifice défini par le récipient.

Abrégé anglais

A method for storing a solution containing acyclovir and a pharmaceutical
product containing an acyclovir solution. The method includes the steps of
providing a predetermined volume of an acyclovir solution suitable for
parenteral administration to a patient and providing a container constructed
to contain the predetermined volume. The container is constructed from a
material containing polymethylpentene and defines an opening. The acyclovir
solution is placed into the container. The method further includes the step of
providing a stopper configured to seal fluidly the opening defined by the
container. The container is then sealed using the stopper. The pharmaceutical
product includes an acyclovir solution contained by a container constructed
from a material containing polymethylpentene. The container defines an opening
therethrough. The product further includes a stopper coated with a fluorinated
resin. The stopper fluidly seals the opening defined by the container.

Revendications

What is claimed is:
1. A method for storing a solution containing
acyclovir, said method comprising the steps of:
providing a predetermined volume of a first solution
comprising acyclovir, said first solution being suitable for parenteral
administration to a patient;
providing a container constructed to contain said
predetermined volume of said first solution, said container constructed
from a material comprising polymethylpentene, said container
defining an opening;
placing said first solution in said container;
providing a stopper configured to seal fluidly said opening
defined by said container; and
sealing said opening defined by said container with said
stopper.
2. A method for storing a solution containing acyclovir
in accordance with Claim 1, wherein said stopper is coated with a
fluorinated resin.
3. A method for storing a solution containing acyclovir
in accordance with Claim 2, wherein said fluorinated resin is selected
from a group consisting of tetrafluoroethylene polymer,
trifluorochloroethylene polymer, tetrafluoroethylene-
hexafluoropropylene copolymer, fluorovinyldene polymer, vinylidene
fluoride polymer, vinyl fluoride polymer, tetrafluoroethylene-ethylene
copolymer, ethylene-tetrafluoroethylene copolymer, and
perfluoroalkoxy polymer.
4. A method for storing a solution containing acyclovir
in accordance with Claim 2, wherein said fluorinated resin is selected
from a group consisting of tetrafluoroethylene polymer,
trifluorochloroethylene polymer,

tetrafluoroethylene-hexafluoropropylene copolymer, vinylidene fluoride polymer, vinyl
fluoride polymer, and tetrafluoroethylene-ethylene copolymer.
5. A method for storing a solution containing acyclovir in
accordance with Claim 1, wherein said stopper is pierceable by a
hypodermic needle.
6. A method for storing a solution containing acyclovir
in accordance with Claim 1, wherein said stopper is pierceable by a
blunt cannula.
7. A method for storing a solution containing acyclovir
in accordance with Claim 1, wherein said step of providing a first
solution containing acyclovir comprises the steps of providing
predetermined volume of a lyophilized acyclovir and reconstituting said
lyophilized acyclovir.
8. A pharmaceutical product comprising:
a container constructed from a composition comprising
polymethylpentene, said container defining an opening;
a stopper coated with a fluorinated resin, said stopper
fluidly sealing said opening defined by said container; and
a solution containing acyclovir fluidly sealed within said
container.
9. A pharmaceutical product in accordance with
Claim 9, wherein said stopper is coated with a fluorinated resin.
10. A pharmaceutical product in accordance with
Claim 9, wherein said fluorinated resin is selected from a group
consisting of tetrafluoroethylene polymer, trifluorochloroethylene
polymer, tetrafluoroethylene-hexafluoropropylene copolymer,
fluorovinyldene polymer, vinylidene fluoride polymer, vinyl fluoride
polymer, tetrafluoroethylene-ethylene copolymer,

ethylene-tetrafluoroethylene copolymer, and perfluoroalkoxy polymer.
11. A pharmaceutical product in accordance with
Claim 9, wherein said fluorinated resin is selected from a group
consisting of tetrafluoroethylene polymer, trifluorochloroethylene
polymer, tetrafluoroethylene-hexafluoropropylene copolymer,
vinylidene fluoride polymer, vinyl fluoride polymer, and
tetrafluoroethylene-ethylene copolymer.

Description

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AQUEOUS ACYCLOVIR FOR3V[DLATION
AND MEI'HOD FOR STORD~G SAME
RaçkFround
The present invention relates to an aqueous formulation of
acyclovir and a method for storing such a formulation. More
particularly, the present invention is directed to a method for storing
a~ueous acyclovir using materials that do not produce particulate
matter when exposed to the high pH levels of the acyclovir solution.
0 Acyclovir, 2-~mino-1,9-dihydro-9-~(2-hydroxy-ethoxy)methyl]-6H-
purin-6-one, is an antiviral agent that has been known for
approximately twenty years. Acyclovir is comm~rcially distributed in
three principal form~ ionq, a tablet formulation for oral
~miniRtration, a cream formulation for topical ~AminiRtration, and a
15 lyophilized powder which must be reconstituted prior to parenteral
~Amini.qtration to a patient. Rsccmqtitution requires the labor of a
medical professional, thereby increasing the end cost of the acyclovir to
the patient while sim lltaneously decreasing convenience for the
medical professional. In addition, if proper precautions are not taken,
~o there is a possibility that the reconstitution will not be performed
aseptically, thereby exposing the patient to a risk of infection. Finally,
reconstitution often is performed using a standard syringe, thereby
exposing the medical professional to a possible needle stick. Because it
is necessary in many health care facilities to report all incidents of
25 needle sticks without regard to whether the stick occurred with a dirty
or clean needle, an increased risk of needle sticks gives rise to an
increase in the ~miniRtrative costs associated with tr~ckinF such
sticks, thereby further increasing the end cost to the patient. For these
reasons, it is desirable to have an acyclovir product that is delivered to
30 the health care facility in a solution form, thus obviating the need for
~ reconstitution.
The pH of an acyclovir solution typically exceeds 11. Storage of
solutions having such high pH levels is difficult due to the fact that
most st~ rd container and stopper materials will produce
35 particulate when exposed to these pH levels for more than a few hours.
For example, plastic vials and stoppers with and without PI FE

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coatings have been found to release calcium stearate (a processing aid
and lubricant) when exposed to high pH levels. Glass vials also have
been found to release particulate when exposed to high pH levels. For
obvious reasons it is undesirable to have these foreign particulate in an
acyclovir solution to be injected into a p~tient Accordingly, it is
desirable to identify a method for storing an acyclovir solution that will
not produce foreign particulate in the solution.
mm?~rv of the Invention
0 The method of the present invention is directed to a method for
storing acyclovir in a solution formulation. In the c l~ime~l method, ar
acyclovir solution and a cor~t~in.qr constructed from a
polymethylpentene-cont~inin~ material are provided. The acyclovir
solution is placed in the container. A stopper constructed to seal lluidly
the cont~inçr also is provided. The cont~inçr is then sealed with the
stopper. In addition, the present invention includes a pharmaceutical
product that includes an acyclovir solution fluidly contained within a
container constructed from a polymethylpentene-cont~ining material.
The container is fluidly sealed by a stopper having a fluorinated resin
ao coating.
~rief Descri~tion of the Draw;n~
For a more complete underst~n~ling of the present invention,
reference may be had to the following Detailed Description read in
2~ connection with the accompanying drawings in which:
FIG. 1 is an exploded view of a pharmaceutical product in
accordance with the present invention.
T)ef ~iled Description
A pharmaceutical product prepared in accordance with the
present invention is generally indicated at 10 of FIG. 1.
Pharmaceutical product 10 includes a container 12 constructed of a
material cont~inin~ polymethylpentene. For example, container 12 can

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be constructed from a material such as "Daikyo Resin CZ~
manufactured and distributed by the Daikyo/Pharma-Gu~i/VVest
Group. In the preferred embodiment depicted in FIG. 1, cont~iner 12 i8
configured as a pharmaceutical vial. However, it will be appreciated
5 that cont~iner 12 can have a variety of forms without departing from
the inten~etl spirit and scope of the present inv~ntion. The size of
container 12 is selected such that cnnt~iner 12 can contain a
predetermined volume of acyclovir solution 16. Container 12 preferably
~l~fines an opening 14 to facilitate the filling of coIlt~in~r 12 and to
o provide access to the contents of cQnt~iner 12. Acyclovir solution 16 can
be either a reconstituted lyophi~i~ed acyclovir solution or a pre-
lyophili7:~tion acyclovir solution.
Stopper 18 is constructed to seal opening 14, thereby fluidly
sealing acyclovir solution 16 within cont~;ner 12. Stopper 18 can be
1~ constructed to be pierceable by a st~n~rd hypodermic needle and/or by
a blunt c~nn~ Stopper 18 can be constructed of a variety of known
materials. In one embodiment, stopper 18 is constructed of a material
coated with a fluorinated resin such as tetrafluoroethylene polymer,
trifluorochloroethylene polymer, tetrafluoroethylene-
ao hexalluofoyloyylene copolymer, fluorovinyldene polymer, vinylidenefluoride poly~ner, vinyl fluoride polymer, tetrafluoroethylene-ethylene
copolymer, ethylene-tetrafluoroethylene copolymer, and
perfluoroalkoxy polymer. In another embo~liment of the present
invention, stopper 18 is coated with a fluorinated resin selected from a
25 group consisting of tetrafluoroethylene polymer,
trifluorochloroethylene polyrner, tetrafluoroethylene-
hexafluoluyroyylene copolymer, vinylidene fluoride polymer, vinyl
fluoride polymer, and tetrafluoroethylene-ethylene copolymer. For
e~r,qmple, stopper 18 can be a FLUROT~ ~ stopper manufactured and
30 distributed by the Daikyo/Pharma-Gum~i/VVest Group.
The method of the present invention includes the step of
providing a predetermined volume of an acyclovir solution suitable ~or
parenteral ~tlmini.qtration. The acyclovir solution can be either a
reconstituted lyophilized acyclovir solution or a pre-lyophili~tion

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acyclovir solution. The method of the present invention further
includes the step of providing a container constructed from a material
cont~inin~ polymethylp~ntene. For example, the container can be
constructed from a material such as "Daikyo Resin CZ~ m~nl~f~ctured
and distributed by the Daikyo/PhaIma-Gummi/West Group. The
container is configured to cont~in a predetermined volume of ~he
acyclovir solution. In the preferred embo~iment of the method of the
present invention, the cont~inar is in the form of a pharmaceutical vial
having an opening.
0 The predetermined volume of acyclovir solution is placed into the
container using a variety of known filling techniques. Next, a stopper
configured to seal fluidly the opening defined by the container is
provided. ~topper 18 can be constructed to be pierceable by a st~n-1~rd
hypodermic needle and~or by a blunt cannula. ~;topper 18 can be
constructed of a variety of materials, including materials coated with a
fluorinated resin such as tetrafluoroethylene polymer,
trifluorochloroethylene polyIner, tetrafluoroethylene-
hexafluoropropylene copolymer, fluorovinyldene polymer, vinylidene
~uoride polymer, vinyl fluoride polymer, tetrafluoroethylene-ethylene
ao copolymer, ethylene-tetrafluoroethylene copolyn~er, and
perfluoroalkoxy polymer. In one embodiment of the method of the
present invention, stopper ~8 is coated with a fluorinated resin selected
from a group consisting of tetraffuoroethylene polymer,
trifluorochloroethylene polymer, tetrafluoroethylene-
2E; hexafluoloplopylene copolymer, vinylidene fluoride polymer, vinyl
fluoride polymer, and tetrafluoroethylene-ethylene copolymer. For
~mple, stopper 18 can be a FLUROTECG~ stopper manufactured and
distributed by the DaikyoJPharma-Gummi/West Group. The stopper is
constructed to seal fluidly the opening defined by the container.
Finally, the stopper is placed over the opening defined by the cont.~iner
so as to seal fluidly the acyclovir solution within the container.
Although the method and pharmaceutical product 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

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various modifications can be made to the invention without departing
from the spirit and scope of the invention disclosed herein as ~l~qimeA
in the appended claims.

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