FORM 2
THE PATENTS ACT,1970 (39 of 1970)
& THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
[See section 10, Rule 13]
CONTAINER FOR ANAESTHETIC AGENTS;
PIRAMAL HEALTHCARE LTD., A COMPANY INCORPORATED UNDER THE COMPANIES ACT, 1913, WHOSE ADDRESS IS PIRAMAL TOWER, GANPATRAO KADAM MARG, LOWER PAREL, MUMBAI 400 013, MAHARASHTRA, INDIA
THE FOLLOWING SPECIFICATION
PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BEE PERFORMED.

FIELD OF THE INVENTION
The present invention relates to a container for inhalation anesthetic agents.
DESCRIPTION OF THE BACKGROUND ART
Traditionally, various anesthetic agents such as sevoflurane (fluoromethyl-2,2,2-trifluoro/l/ (trifluoromethyl) ethyl ether), desflurane (2-difluromethyl 1,2,2,2-tetrafluoroethyl ether), isoflurane {l-chloro-2, 2,2-trifluoroethyl difluoromethyl ether), enflurane (2-chloro-1, 1, 2-trifluoroethyl difluoromethyl ether), rnethoxyflurane (2,2-dichloro-1,1-difluoroethyl methyl ether) and haloethane (2-bromo-2chloro-l, I, l-trifluoroethane) are packed in glass containers. The concern is that the reaction of the anesthetic agents with glass bottles may take place due to the presence of Lewis acid in the composition of glass bottles. To overcome this problem, various efforts have been made to inhibit the reactivity of glass. 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.
Further, the breakage concern of the glass is of prime consideration especially when these bottles are used for storing and transporting the anesthetic agents. Any accidental breakage of the glass bottles will expose the anesthetic agent to environment and also cause harm to people handling it.
To solve above problems, WO 99/34762 discloses a pharmaceutical product comprising of a container having a fluoroether containing anesthetic in the interior space of the container. The container is constructed from compounds selected from the group consisting of polyethylene naphthalate, polymethylpentene, polypropylene, polyethylene, ionomeric resins and combinations thereof. The anesthetic is selected from sevoflurane, enflurane, isoflurane, rnethoxyflurane and desflurane. The container is further defined as having an opening which provides fluid communication between the interior space of the container and the external environment. The pharmaceutical product comprises a cap which is made up of material selected from polyethylene naphthalate, polymethylpentene, polypropylene, polyethylene, ionomeric resins and combinations thereof. This invention also discloses a

method of storing the anesthetic agents.
WO 02/22195 discloses a container for liquid inhalation anesthetics, more particularly, an aluminium container that is suitable for storing halogenated inhalation anesthetics is described. The halogenated inhalation anesthetics used in this invention include sevoflurane (fluorornethyl-2,2,2-trifluoro/1/ (trifluoromethyl) ethyl ether), desflurane- (2-difluromethyl 1,2,2,2-tetrafIuoroethy! ether), isoflurane (l-chloro-2, 2,2-trifIuoroefhyl difluoromethyl ether), enflurane (2-chloro-1, 1, 2-trifluoroethyl difluorcmethyl ether), methoxyflurane (2,2-dichIoro-1,1-difluoroethyl methyl ether) and halothane (2-bromo-2chloro-l, I, l-trifluoroethane), all of which are liquids at ambient conditions. However, these containers are expensive.
WO 2006/019795 discloses an inhalation anesthetic product comprising a container, an inhalation anesthetic and a volume of fluoroether inhalation anesthetic. The container is made up of or lined with a material comprising of acrylonitrile , methyl acrylate and butadiene, said container defining an interior space constructed to contain therein, external to a patient's body, an inhalation anesthetic; and a volume of sevoflurane contained in said interior space defined by said container. As taught therein, these efforts increases the cost of the containers and do not encounter the above discussed problem related to degradation which can occur when using glass to contain fluoroether containing inhalation anesthetic agents.
Hence, there remains a need to find containers for storing. Carrying and handling inhalation anesthetic agents solving one or more problems as discussed above.
SUMMARY OF THE INVENTION:
Accordingly, the present invention in one embodiment provides a container for anesthetic agents defining an opening therein, said opening providing fluid communication between said interior space defined by said container and an external environment of said container and a cap/closure constructed to seal said opening defined in said container wherein said container is constructed from a material comprising a compound selected from the group consisting of polysulfone, a coplymer of polyphenyloxide and polystyrene, copolyster of

polycyclohexylenedimethylene terephthalate, polycyclohexylenedimethylene terephthalate glycol and polyetherimide either alone or in combination thereof, said container defining an interior space; and a volume of a fluoroether -containing inhalation anesthetic contained in said interior space defined by said container wherein the said container provides a barrier to water vapour transmission into and out of the container.
In another embodiment, the present invention provides a container for anesthetic agents, said container defining an interior space, said container having an interior surface adjacent to said interior space in the form of coating or linings, said interior surface constructed from a material comprising a compound selected from a group consisting of polysulfone, a coplymar of polyphenyloxide and polystyrene, copolyster of polycyclohexylenedimethylene terephthalate, polycyclohexylenedimethylene terephthalate glycol and polyetherimide either alone or in combination thereof wherein the said interior surface provides a barrier to water vapour transmission into and out of the container.
According to the present invention, the container further comprises comprising a valve assembly with a resilient means so as to check on the flow of the materials and/or with a cap/closure thereon, said valve assembly and/or cap/closure can be made up of materia! comprising a compound selected from the group consisting of polysulfone, a coplymer of polyphenyloxide and polystyrene, copolyster of polycyclohexylenedimethylene terephthalate, polycyclohexylenedimethylene terephthalate glycol and polyetherimide alone or in combination thereof, the said container further has an orifice or an opening to fill in or remove the anesthetic agent.
DESCRIPTION OF THE INVENTION:
The present invention provides for a pharmaceutical product comprising of a container and
anesthetic agent (s) held within the container. The container is constructed from materials
comprising of polysulfone, a coplymer of polyphenyloxide and polystyrene, copolyster of
polycyclohexylenedimethylene terephthalate, polycyclohexylenedimethylene terephthalate
glycol and polyetherimide either alone or in combination thereof.
Alternatively, The container defining an interior space may have an interior surface adjacent

to said interior space in the form of coating or linings, said interior surface constructed from a material comprising a compound selected from a group consisting of polysulfone, a Coplymer of polyphenyloxide and polystyrene, copolyster of polycyclohexylenedimethylene terephthalate, polycyclohexylenedimethylene terephthalate glycol and polyetherimide either alone or in combination thereof wherein the said interior surface provides a barrier to water vapour transmission into and out of the container and the container can be made of any known cheap polymer or metal or glass.
The anesthetic agent is carried within the container in an interior space defined by the container. The anesthetic agents are fluoroethers selected from sevoflurane (fluoromethyl-2,2.2-trifluoro/l/ (trifluoromethyl) ethyl ether), desflurane (2-difluromethyl 1,2,2,2-tstrafluoroethyl ether), isoflurane (l-chloro-2, 2,2-thfluoroethyl difluoromethyl ether), enflurane (2-chloro-1, 1, 2-trifiuoroethyl difluoromethyl ether), methoxyflurane (2,2-dichloro-1,1-difluoroethyl methyl ether) and halothane (2-bromo-2chloro-l, I, l-trifluoroethane). The materials of constructions used to manufacture the container do not react with the anesthetic agent. The container being non-reactive with the anesthetic agent makes it non-hazardous as well as increases the shelf life of the anesthetic agent.
The container comprises of a closure or a cap. Alternatively, the container may have a
closure with a valve assembly with a resilient means so as to put a check on the flow of the
materials or anesthetic agent (s) with a cap thereon. The valve assembly and/or cap/closure
can be made up of materials comprising of polysulfone, a coplymer of polyphenyloxide and
polystyrene, copolyster of polycyclohexylenedimethylene terephthalate,
polycyclohexylenedimethylene terephthalate glycol and polyetherimide alone or in combination thereof.
Further, the container has an orifice or an opening to fill in or remove the anesthetic agent (s). The container can have a screw-on type design of the neck. The Screw-On type design of the neck supports the closure, and is tightly screwed-on, the bottle to avoid any leakage or- spillage of the material inside the bottle. Alternatively, the bottle can have a Snap-On type nsck design. The Snap-On type neck design supports the closure and is snap-fitted on the

bottle to avoid any leakage or spillage of the material from inside the bottle. The container of the present invention is unbreakable and hence will withstand the detrimental effects that are experienced during transit. This prevents any breakage thus avoids leakage and circumvents economic loss. The container also provides good barrier to water vapour transmission into and out of the container. The material allows the thickness and weight of the bottle to be optimized so as to support the desired load bearing and transmission in and out of the container.
The container of the present invention can be designed to contain a specific amount of the material for example 100 ml or 250 ml capacity but this can be varied depending upon the amount of anesthetic agent required to be filled in. Moreover, the material of the container of the present invention is not reactive with the anesthetic agent
The container as mentioned in the foregoing can be designed to connect to a vaporizer or key filler or both for dispensing the anesthetic agent (s) contained within it. The container is manufactured using Injection Stretch Blow Molding process on a single stage machine. The manufacturing of the container is done at specific process parameters suitable for a particular polymer. The container so manufactured under the controlled process parameters with the said materials of construction, provides a very good solution for storing and transporting the inhalation anesthetic agents like sevoflurane, desflurane, enflurane, methoxyflurane, haloethane and the like and preferably sevoflurane. While the present invention has been described herein with respect to the various exemplary embodiments, it will be apparent to one of the ordinary skill in the art that many modifications, improvements and sub combinations of the various embodiments, adaptations and variations can be made to the invention without departing from the spirit and the scope thereof. Example 1:
Different tests were carried out to study the compatibility of anesthetic agents sevoflurane with bottles made up of different material as claimed for 6 months. The tests included the product testing and the bottle testing. 1) Product testing

In product testing various tests were conducted for measuring the product loss, appearance, refractive index, acidity or alkalinity, non volatile residue, fluorides, water and related substances.
The product loss was measured by measuring the difference in the initial weight of bottle and final weight of bottle.
The identification was carried out by the method of Infrared spectrophotometry. The related substances were tested by the method of Gas chromatography.
2) Bottle testing-
The bottle testing was conducted for appearance, colour and brittleness/swelling The results achieved are tabulated as table 1, 2 and 3 be|0w:

TABLE 1

BOTTLE RESIN POLYPHENYLOXIDE + POLYSTYRENE
SR. NO TEST LIMITS TIME

"0" 30 6 C/65%RH 40°C/75%RH

(INITIAL ANALYSIS) 1M 3M 1M 3M

PRO 3UCT TESTING
1 PRODUCT LOSS (WEIGHT/VOLUME) FOR RECORDS + 0.5g + 0.5g + 0.8g + 0.6g
2 WATER CONTENT NMT 130ppm 71 958 ppm 1080 ppm lOOOppm 1510 ppm
3 METAL ION ANALYSIS ( ICP )
ALUMINIUM FOR RECORDS 1.0 ppm 1.2 ppm - <1.0 ppm <1.0 ppm
CALCIUM FOR RECORDS 1.0 ppm 2.6 ppm - 3.93 ppm 2.8 ppm
POTASSIUM FOR RECORDS <1.0 ppm <1.0 ppm 1.83 ppm <1.0 ppm
SODIUM FOR RECORDS 1.5 ppm 2.3 ppm 1.03 ppm 6.5 ppm
4 NON VOLATILE RESIDUE (NVR) NMT 1.0 mg/ 10 ml 0.1 mg/lOml O.lmg/lOml O.lmg/lOml O.lmg/lOml O.lmg/lOml
5 ACIDITY OR ALKALINITY NMT 0.10ml OF COMPLIES COMPLIES COMPLIES COMPLIES COMPLIES

O.OlON NaOH OR

NMT 0.60 ml OF

0.010N HCL FOR

NEUTRALIZATION

6 APPEARANCE OF
SOLUTION
(TURBIDITY) FOR RECORDS CLEAR COLORLESS CLEAR COLORLESS CLEAR COLORLESS CLEAR
COLORLESS CLEAR
COLORLESS
7 LIMIT OF FLUORIDE NMT 2ug/ml <0.2ug/ml <0.2ug/m| <0.2ug/ml <0.2ug/ml <0.2ug/ml
8 RELATED COMPOUNDS (
BY GC)
RELATED COMPOUNDS-A NMT25ug/g ND ND ND ND ND
RELATED COMPOUNDS-B NMT50ug/g ND ND ND ND ND
ANY OTHER INDIVIDUAL IMPURITY NMT25ug/g 10 ug/g ND ND ND ND
TOTAL IMPURITIES NMT 50ug/g 22 ug/g ND ND ND ND
BOTT .E TESTING
1 APPEARANCE FOR RECORDS BLACK BLACK BLACK BLACK BLACK
2 COLOUR FOR RECORDS BLACK BLACK BLACK BLACK BLACK
3 BRITTLENESS/SWELLING FOR RECORDS NO CHANGE OBSERVED

TABLE 2
ROTTI F RESIN POLYCYCLOHFXYLENE-DIMETHYLENE TEREPTHALATE
SR. NO TEST LIMITS TIME

"0" 30 ° C/65%RH 40°C/75%RH

(INITIAL ANALYSIS) 1M 3M 1M 3M

PRODUC IT TESTING
1 PRODUCT LOSS (WEIGHT/VOLUME) FOR RECORDS .... 0.0 g -O.1g -0.4g -1.7g
2 WATER CONTENT NMT130pprn 71 610 ppm 1060 ppm 1040 ppm 1550 ppm
3 METAL ION ANALYSIS (ICP)
ALUMINUM FOR RECORDS 1.0 ppm 1.Oppm - <1.0 ppm <1.0ppm
CALCIUM FOR RECORDS 1.0 ppm 2.0 ppm - 2.17 ppm 3.4 ppm
POTASSIUM FOR RECORDS <1.0ppm <1.0 ppm 1.28 ppm 1.4 ppm
SODIUM FOR RECORDS 1.5 ppm 2.7 ppm <1.0 ppm 1.6 ppm
4 NON VOLATILE RESIDUE (NVR) NMT1.0mg/10 ml 0.1mg/10 ml O.1mg/lOm 1 O.1mg/10 ml O.1mg/lOm 1 0.1mg/10 ml
5 ACIDITY OR
ALKALINITY NMT 0.10ml OF 0.010N NaOH OR NMT 0.60 ml OF 0.010NHCLFOR NEUTRALIZATION COMPLIES COMPLIES COMPLIES COMPLIES COMPLIES
6 APPEARANCE OF SOLUTION (TURBIDITY) FOR RECORDS CLEAR COLORLESS CLEAR COLORLESS CLEAR COLORLESS CLEAR COLORLE5S CLEAR COLORLES
S
7 LIMIT OF FLUORIDE NMT 2ug/ml <0.2ug/ml <0.2ug/ml <0.2ug/ml <0.2ug/ml <0.2ug/m1
8 RELATED COMPOUNDS (BY GC)
RELATED COMPOUNDS-A NMT 25ug/g ND ND ND ND ND
RELATED COMPOUNDS-B NMT 50ug/g ND ND ND ND ND
ANY OTHER INDIVIDUAL IMPURITY NMT 25ug/g 10 ug/g ND ND ND ND
TOTAL IMPURITIES NMT 50ug/g 22 ug/g ND ND ND ND
BOTTLE TESTING
1 APPEARANCE FOR RECORDS COLOUR
LESS COLOUR LESS COLOUR LESS COLOUR LESS COLOUR LESS
2 COLOUR FOR RECORDS COLOUR
LESS COLOUR LESS COLOUR LESS COLOUR LESS COLOUR
LESS
3 BRlTTLENESS/SWELLING FOR RECORDS NO CHANGE OBSERVED

TABLE 3

BOTTLE RESIN POLYETHRIMIDE
SR. NO TEST LIMITS TIME

"0" 30°C/65%RH 40°C/75%RH

(INITIAL ANALYSIS) 1M 3M 1M 3M
PRO DUCT TESTING
1 PRODUCT LOSS (WEIGHT/VOLUME) FOR RECORDS .... + 0.6g + 0.6g + 0.8g + 0.8g
2 WATER CONTENT NMT130ppm 71 ppm 850 ppm 1070 ppm llOOppm 1450 ppm
3 METAL ION ANALYSIS (ICP }
ALUMINIUM FOR RECORDS 1.0 ppm 1.0 ppm - <1.0ppm <1.0ppm
CALCIUM FOR RECORDS 1.0 ppm 1.0 ppm - 2.07 ppm 2.2 ppm
POTASSIUM FOR RECORDS <1.0 ppm <1.0ppm <1.0 ppm <1.0 ppm
SODIUM FOR RECORDS 1.5 ppm 1.4 ppm <1.0 ppm 1.7 ppm
4 NON VOLATILE RESIDUE (NVR) NMT1.0mg/10 ml O.1mg/1Oml O.1mg/1Oml O.1lmg/1Oml O.1lmg/ 10ml O1mg/1Oml
5 ACIDITY OR ALKALINITY NMT 0.10ml OF COMPLIES COMPLIES COMPLIES COMPLIES

0.010N NaOH OR

NMT0.60ml OF



COMPLIES

0.010N HCL FOR

NEUTRALIZATION




6 APPEARANCE
OF SOLUTION (TURBIDITY) FOR RECORDS CLEAR
COLORLESS CLEAR COLORLESS CLEAR COLORLESS CLEAR COLORLESS CLEAR COLORLESS
7 LIMIT OF FLUORIDE NMT2ug/ml <0.2ug/ml <0.2ug/ml <0.2ug/ml <:0.2ug/ml <0.2ug/ml
8 R ELATED COMPC )UNDS(BY GC )
RELATED
COMPOUNDS-A NMT25ug/g ND ND ND ND ND
RELATED COMPOUNDS-B NMT50ug/g ND ND ND ND ND
ANY OTHER INDIVIDUAL IMPURITY NMT25ug/g 10 ug/g ND ND ND ND
TOTAL IMPURITIES NMT50ug/g 22 ug/g ND ND ND ND
BOT HE TESTING
1 APPEARANCE FOR RECORDS YELLOW YELLOW YELLOW YELLOW YELLOW
2 COLOUR FOR RECORDS YELLOW YELLOW YELLOW YELLOW YELLOW
3 BRITTLENESS/SWELLING FOR RECORDS NO CHANGE OBSERVED

Conclusion:
The above tests indicate that the proposed container is suitable for use with anesthetic agents
and the product passes the relevant pharmacopeia requirement.

WE CLAIM:
1) A container for anesthetic agents with a cap defining an opening therein, said opening providing fluid communication between said interior space defined by said container and an external environment of said container and a cap/closure constructed to seal said opening defined in said container wherein said container is constructed from a materia! comprising a compound selected from the group consisting of polysulfone, a coplymer of polyphenyloxide and polystyrene, copolyster of polycyclohexylenedimethylene terephthafate, polycyclohexylenedimethylene terephthalate glycol and polyetherimide either alone or in combination thereof, said container defining an interior space; and a volume of a fluoroether containing inhalation anesthetic contained in said interior space defined by said container wherein the said container provides a barrier to water vapour transmission into and out of the container.
2) A container for anesthetic agents, said container defining an interior space, said container having an interior surface adjacent to said interior space in the form of coating or linings and a cap/closure constructed to seal said opening defined in said container, said interior surface constructed from a material comprising a compound selected from a group consisting of polysulfone, a coplymer of polyphenyloxide and polystyrene, copolyster of polycyclohexylenedimethyiene terephthalate, polycyclohexylenedimethylene terephthalate glycol and polyetherimide either alone or in combination thereof; and a volume of a fluoroether containing inhalation anesthetic contained in said interior space defined by said container wherein the said interior surface provides a barrier to water vapour transmission into and out of the container.
3) The container for anesthetic agents as claimed in any one of the preceding claims, wherein said flouroether containing inhalation anesthetic is selected from a group consisting of sevoflurane