FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
THE PROVISIONAL SPECIFICATION
(See section 10)
1. PREPARATION OF METHSCOPOLAMINE TANNATE.
2. CADILA PHARMACEUTICALS LTD., "CADILA CORPORATE CAMPUS", SARKHEJ-DHOLKA ROAD, BHAT, AHMEDABAD, 382210, GUJARAT, INDIA, AN INDIAN COMPANY.
3. THE FOLLOWING SPECIFICATION DESCRIBES AND ASCERTAINS THE NATURE OF THIS INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED.

TITLE : PREPARATION OF METHSCOPOLAMINE TANNATE

FIELD OF INVENTION :
The invention relates to a process for preparing Methscopolamine tannate composition having a purity of about about 93 wt. %, based on the weight of the composition, with the balance comprising primarily water.

BACKGROUND OF THE INVENTION :
Antihistamines are available in the form of free bases as well as salts i.e. hydrochloride, maleate ,
tannate etc. Frequently it is necessary to utilize antihistamines in the form of tannate salt because
such salts are generally quite stable and may be administered in such form without untoward side
effects.
Tannic acid, also known as tannin, is a well known naturally occurring substance. Commercially
available tannic acid usually contains about 5 wt. % water, has a molecular weight of about 1700
and is typically produced from Turkish or Chinese nutgall.
Tannic Acid consists of an amorphous powder glistening scales or spongy masses varying in color
from yellowish-white to light brown. Tannic acid is very soluble in water, glycerine or alcohol.
As there is no published method available for preparing Methscopolamine tannate , it is long felt
need for the industry to develop a commercially viable method for preparing Methscopolamine
tannate on an industrial scale.

SUMMARY OF INVENTION :
The main object of the invention is to provide a process for the preparation of Methscopolamine
tannate composition using commercially available raw materials.
Another object of the invention is to provide such a process that can be carried out in water.
Yet another object of the present invention is to provide a process for the preparation of
Methscopolamine tannate by a synthetic route which results in the production of compositions
having a minimum purity level of at least 90 wt. %, usually atleast 92.5 % based on the weight of
the composition.
The chief "impurity" present in the compositions prepared by the process of the invention is water
which is present in an amount of about 7 wt. %, based on the weight of the composition.
Since the pure antihistamine tannate compositions prepared by the process of the invention is
administered either in solid form, i.e. a pill, or as a suspension, the minimal amount of water present
in the composition cannot be considered to be an impurity of the nature associated with degradation
products or volatile organic compounds such as isopropanol. The dosage to be administered can be
readily adjusted by taking into account the insignificant amount of water present in the composition.

DETAILED DESCRIPTION
Methscopolamine tannate is quaternary salt more specifically , methscopolammonium salt .
Starting materials selected for preparing methscopolammonium tannate are methscopolammonium compounds such as methscopolammonium bromide or chloride or nitrate and their like. In preparing methscopolamine tannate, the anion part of the methscopolammonium salt is exchanged with tannic acid anion. Tannic acid anion is generated by reacting tannic acid with a base. Thus in accordance with the present invention , methscopolamine tannate is prepared by contacting methscopolammonium salt with tannic acid salt in water .
Preferably methscopolamine tannate is prepared by contacting a solution of methscopolammonium
salt in water with tannic acid salt solution in water by following process steps as mentioned below
[A] Preparation of Methscopolammonium salt solution :
Methscopolammonium salt consist of quaternary ammonium cation with one of the following anions such as bromide .chloride, iodide, nitrate, methosulfate, sulfate, phosphate or any other anion , capable of being replaced by tannic acid anion. Methscopolammonium salt is dissolved in water.
The dissolution of Methscopolammonium salt is carried out at 10 to 100°C, preferably at 20 to 40°C.
[B] Preparation of Tannic acid salt solution :
Tannic acid salt is a compound wherein the associated cation is selected from alkali metal such as potassium, sodium, lithium or alkaline earth cations such as calcium, barium. The preferred salt is Tannic acid potassium salt. Tannic acid salt is dissolved in water. The dissolution of Tannic

acid salt salt is carried out at 10 to 100°C, preferably at 20 to 40°C. Tannic acid salt is taken as such or can be freshly prepared.
[C] Preparation of methscopolamine Tannate :
To an aqueous solution of methscopolammonium salt is charged an aqueous solution of tannic acid salt, and stirred at 10 to 100°C, preferably at 20 to 40°C more preferably at 25-30°C to give a slurry of solid mass.
[D] Isolating the compound by Alteration followed by washing with water and drying to give
Methscopolamine tannate.
Methscopolamine tannate on analysis contains 42 % w/w to 48 % w/w on as is basis of Methscopolamine content and 43 % w/w to 52 % w/w on as is basis of tannic acid , % water is not more than 7 % , Residual solvent (here isopropyl alcohol) is not more than 2000 ppm. Description of Methscopolamine tannate is pale yellow to greenish yellow powder.
Having thus described the invention with reference to particular preferred embodiment and illustrative example ,those skilled in the art can appreciate modifications to the invention as described and illustrated that do not depart from the spirit and scope of the invention as disclosed in the specification. The example is set forth to aid in understanding the invention but is not intended to , and should not be construed to , limit the scope in any way.

Example-1 : Preparation of Methscopolamine tannate
Stage-1
Preparation of K-salt of tannic acid.
In 1L capacity multinecked flask equipped with condenser, waterbath , thermometer were
charged Tannic acid (100 gm), 500 ml of 2-propanol and stirred at 40-45°C and stirred at same
temperature for about 15 minutes to get a clear solution.
To it were added a solution of potassium tert. butoxide (60 gms) in 2-propanol (600 ml) at 40-
45°C. The reaction mass was stirred further for 2 hours at 40-45°C.The reaction mass was cooled to
room temperature and stirred for 30 minutes. The reaction mass was filtered and washed with 2x
100 ml of 2-propanol, sucked dry and dried at 50°C under vacuum to give 110-115 gms K-salt.
Stage-2
Preparation of Methscopolamine tannate
In 5 L capacity multinecked flask equipped with , thermometer, waterbath , thermometer were
charged 3500 ml water and 100 gms of Methscopolamine bromide and stirred at about 25-30°C.
The reaction mixture became clear after about 10 minutes stirring at 25-30 C. To it were added a
solution of K-salt of tannic acid (100 gm ) in water (2000 ml) slowly at 25-30°C. The reaction mass
was further stirred for 30 minutes at 25-30°C .The reaction mass was filtered and washed with 2x
100 ml water. The wet cake was taken out and further stirred with 1000 ml water for about 30
minutes , filtered and washed with 2x 100 ml water, sucked dry and dried at 45°C under vacuum to
give Methscopolamine tannate
Wt= 80.0 gms