AQUEOUS ACYCLOVIR FORMULATION AND METHOD FOR STORING SAME

Abstract: 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.

Description: AQUEOUS ACYCLOVIR FORMULATION AND METHOD FOR STORING SAME Background 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 aqueous acyclovir using materials that do not produce particulate matter when exposed to the high pH levels of the acyclovir solution. Acyclovir, 2-amino-l,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 commercially distributed in three principal formulations, a tablet formulation for oral administration, a cream formulation for topical administration, and a lyophilized powder which must be reconstituted prior to parenteral administration to a patient. Reconstitution requires the labor of a medical professional, thereby increasing the end cost of the acyclovir to the patient while simultaneously decreasing convenience for the medical professional. In addition, if proper precautions are not taken, 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 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 administrative costs associated with tracking 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 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 standard container and stopper materials will produce particulate when exposed to these pH levels for more than a few hours. For example, plastic vials and stoppers with and without PTFE 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 patient. Accordingly, it is desirable to identify a method for storing an acyclovir solution that will not produce foreign particulate in the solution. Summary of the Invention The method of the present invention is directed to a method for storing acyclovir in a solution formulation. In the claimed method, an acyclovir solution and a container constructed from a polymethylpentene-containing material are provided. The acyclovir solution is placed in the container. A stopper constructed to seal fluidly the container also is provided. The container 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-containing material. The container is fluidly sealed by a stopper having a fluorinated resin coating. Brief Description of the Drawings For a more complete understanding of the present invention, reference may be had to the following Detailed Description read in connection with the accompanying drawings in which: FIG. 1 is an exploded view of a pharmaceutical product in accordance with the present invention. Detailed 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 containing polymethylpentene. For example, container 12 can be constructed from a material such as "Daikyo Resin CZ" manufactured and distributed by the Daikyo/Pharma-Gummi/West Group. In the preferred embodiment depicted in FIG. 1, container 12 is configured as a pharmaceutical vial. However, it will be appreciated that container 12 can have a variety of forms without departing from the intended spirit and scope of the present invention. The size of container 12 is selected such that container 12 can contain a predetermined volume of acyclovir solution 16. Container 12 preferably defines an opening 14 to facilitate the filling of container 12 and to provide access to the contents of container 12. Acyclovir solution 16 can be either a reconstituted lyophilized acyclovir solution or a pre- lyophilization acyclovir solution. Stopper 18 is constructed to seal opening 14, thereby fluidly sealing acyclovir solution 16 within container 12. Stopper 18 can be constructed to be pierceable by a standard hypodermic needle and/or by a blunt cannula. 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- hexafluoropropylene copolymer, fluorovinyldene polymer, vinylidene fluoride polymer, vinyl fluoride polymer, tetrafluoroethylene-ethylene copolymer, ethylene-tetrafluoroethylene copolymer, and perfluoroalkoxy polymer. In another embodiment of the present invention, stopper 18 is coated with a fluorinated resin selected from a group consisting of tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene- hexafluoropropylene copolymer, vinylidene fluoride polymer, vinyl fluoride polymer, and tetrafluoroethylene-ethylene copolymer. For example, stopper 18 can be a FLUROTEC® stopper manufactured and distributed by the Daikyo/Pharma-Gummi/West Group. The method of the present invention includes the step of providing a predetermined volume of an acyclovir solution suitable for parenteral administration. The acyclovir solution can be either a reconstituted lyophilized acyclovir solution or a pre-lyophilization acyclovir solution. The method of the present invention further includes the step of providing a container constructed from a material containing polymethylpentene. For example, the container can be constructed from a material such as "Daikyo Resin CZ" manufactured and distributed by the Daikyo/Pharma-Gummi/West Group. The container is configured to contain a predetermined volume of the acyclovir solution. In the preferred embodiment of the method of the present invention, the container is in the form of a pharmaceutical vial having an opening. 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. Stopper 18 can be constructed to be pierceable by a standard hypodermic needle and/or by a blunt cannula. Stopper 18 can be constructed of a variety of materials, including materials coated with a fluorinated resin such as tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene- hexafluoropropylene copolymer, fluorovinyldene polymer, vinylidene fluoride polymer, vinyl fluoride polymer, tetrafluoroethylene-ethylene copolymer, ethylene-tetrafluoroethylene copolymer, and perfluoroalkoxy polymer. In one embodiment of the method of the present invention, stopper 18 is coated with a fluorinated resin selected from a group consisting of tetrafluoroethylene polymer, trifluorochloroethylene polymer, tetrafluoroethylene- hexafluoropropylene copolymer, vinylidene fluoride polymer, vinyl fluoride polymer, and tetrafluoroethylene-ethylene copolymer. For example, stopper 18 can be a FLUROTEC® stopper manufactured and distributed by the Daikyo/Pharma-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 container 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 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.

Claims: 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 perfluoro alkoxy 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.

Inventors: KLANDRUD KATHEE E, RHODES LAWRENCE J, KLANDRUD, KATHEE, E., RHODES, LAWRENCE, J.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1996
Main classification: A61J1
IPC codes: A61J1, B65D39