FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
AND
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. TITLE OF THE INVENTION
"Lyophilized powder preparation for Proton- pump inhibitor and process for preparing the same"
2. APPLICANT(S)
(a) NAME: J.B. CHEMICALS AND PHARMACEUTICALS LTD.
(b) NATIONALITY: An Indian Corporation
(c) ADDRESS: Neelam Centre, B- Wing, 4,h floor, Hind Cycle Road, Worli, Mumbai 400 030,
Maharastra, India
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

Technical Field of the Invention
The present invention in general relates to the field of pharmaceutical preparation and in particularly describes lyophilized pantoprazole (5-difluromethoxy-2-[(3, 4-dimethoxy-2-pyridinyl) methylsulfinyl]-1H-benzimidazole) preparations obtained by freeze-drying of an aqueous solution of pantoprazole and mannitol.
Prior Art
Pantoprazole, 5-difluromethoxy-2-[{3, 4-dimethoxy-2-pyridinyl) methylsulfinyl]-1H-benzimidazole is a benzimidazole compound disclosed in EP 0166287B that inhibits gastric acid secretion. Pantoprazole sodium has been approved for parenteral administration for short-term treatment of erosive esophagitis associated with gastroesophageal reflux disease (GEHD), for maintenance of healing of erosive esophagitis and for treatment of pathological hypersecretory conditions, including, for example, Zollinger-Ellison syndrome. Pantoprazole sesquihydrate sodium is preferably used for intravenous administration.
In past years, pantoprazole sodium for injection was commercially available as a freeze-dried powder in a clear glass that fitted with a rubber stopper and crimp seal containing only pantoprazole sodium. However, the present available product presented an important drawback, i.e., a precipitate was formed when the reconstituted drug was mixed with IV solutions, and hence an-line filter should be used for intravenous administration, making the administration troublesome.
Aimed to reduce the number of particles after reconstitution, and thus to eliminate the requirement of an in-line filter, US Patent No. 6,780,881 describes that by freeze drying of an aqueous solution of pantoprazole, ethylenediamine tetraacetic acid and/or suitable salt thereof, and sodium hydroxide and/or sodium carbonate to regulate the pH of the solution, a lyophilisate is obtained having significantly lower number of subvisible particles after reconstitution with a solvent compared to lyophilisates of the state of the art.
WO9402141 describes an injection comprising a 2-[(2-pyridyl) methylsulfinyL]-benzimidazole compound an aqueous solvent, wherein the pH of the injection is not less than 9.5 and not more than 11.5. It is mentioned that said injection does not cause hemolysis and cause less local irritation.
DE 43 24 014 describes the preparation of a lyophilisate of pantoprazole-sodium sesquihydrate in the presence of sucrose as an auxiliary at production temperatures of -25 to -30.degree. C. It is disclosed that the lyophilisate is of improved storage stability and can be stored at room temperature for at least 18 months and is easily reconstituted in liquid form in suitable doses for use.
CN 1235018 describes a freeze-dried injection powder of pantoprazole sodium containing no crystallised water with pH value of 9-12.5, which is composed of pantoprazole sodium, freeze-dried powder supporting agent, metal ion complexing agent and pH regulator.
W099/18959 describes aqueous pharmaceutical compositions which are chemically and physically stable for intravenous injection which comprise anti-ulcerative compound and glycine as stabilizer in carrier.

There still exits a need for alternative formulation suitable for parenteral administration of pantoprazole sodium sesquihydrate which possesses sufficiently storage stability.
Summary of the Invention
The invention relates to lyophilized preparations of pantoprazole sodium for injection that include mannitol as inactive ingredient, and to a process for their preparation. The invention further includes pantoprazole sodium for injection obtained by reconstitution of the lyophilized products described herein.
Detailed Description of the Preferred Embodiments
Reference will now be made in detail to the preferred embodiments of the invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In addition, and as will be appreciated by one of skill in the art, the invention may be embodied as a method, system or process.
The invention provides new lyophilized preparations of pantoprazole sodium for injection that includes mannitol, and to a process for their preparation. The invention further includes pantoprazole sodium for injection obtained by reconstitution of the lyophilized products described herein.
According, one aspect of the invention relates to a new lyophilized preparation for injection that includes 45.1 mg of pantoprazole sodium sesquihydrate which is equivalent to 40.0 mg of pantoprazole and 45.0 mg of
mannitol.
In another aspect, the invention relates to a process for preparing the above-described lyophilized preparations for injection. In another aspect, the invention provides pantoprazole sodium injections obtainable by reconstitution of the lyophilized products described herein.
Another embodiment of the invention provides a process for preparing the above-described lyophilized preparation for injection that includes the following steps: bubbling nitrogen gas through water for injection and heating water to 65°C; adding mannitol under constant stirring to the solution which is allowed to cool to 50aC and nitrogen is bubbled through solution to obtain a solution; adding pantoprazole sodium to the solution which is allowed to cool to room temperature and nitrogen is bubbled through solution to obtain a solution; adjusting volume of the solution using water of injection; filtering the solution through 0.2 micron sterile nylon membrane filter, filling the solution into a vial, lyophilizing the solution and closing the vial under nitrogen atmosphere.
A pantoprazole injection according to the invention can be produced by dissolving the lyophilized product thus obtained in a suitable solvent for example distilled water for injection. Preferably the pantoprazole injection according to the invention is used in the form of intravenous injection.

The production of the lyophilized product and pantoprazole injection is described by way of example below. The following examples illustrate the invention in greater detail, without restricting it.
Example 1

Sr. No. Ingredients Quantity per vial (mg)
1. Pantoprazole sodium sesquihydrate equivalent to pantoprazole 45.1 40.0
2. Mannitol 45.0
Manufacturing Procedure
The lyophilized preparation of pantoprazole sodium for injection of Table 1 was prepared as follows: required amounts of pantoprazole sodium and mannitol were dissolved in water for injection under nitrogen atmosphere, until each of the ingredients dissolved completely. After a clear solution is obtained, the volume is made up with water for injection. The solution was then filtered through 0.2 micron sterile nylon membrane filter and filled into a vial under nitrogen atmosphere. The vial was fitted with a rubber stoppers and was lyophilized (i.e. freeze-dried) by a conventional method to yield a lyophilized product that was ready for reconstitution.

Claims
1. A lyophilized pantoprazole sodium preparation for injection comprising (a) 45.1 mg of pantoprazole sodium and 45.0 mg of mannitol.
2. A process for preparing a lyophilized pantoprazole sodium preparation comprises step of: obtaining a solution by adding pantoprazole sodium in water for injection purged with nitrogen gas, adding mannitol to the solution, adjusting volume of the solution by adding additional water for injection purged with nitrogen gas, filtering the solution through a membrane filter, filling the solution into a vial and lyophilizing the solution to obtain a lyophilized product.
3. The process of claim 2 wherein pantoprazole sodium comprises 45,1 mg of pantoprazole sodium sesquihydrate.
4. The process of claim 2 wherein mannitol comprises 45.0 mg of mannitol.
5. The lyophilized pantoprazole sodium preparation of claim 1, wherein the preparation is provided for intravenous administration.