THE PATENTS ACT, 1970 (39 of 1970)
COMPLETE SPECIFICATION
A PROCESS OF PREPARING TABLET DOSAGE FORM OF AZITHROMYCIN MONOHYDRATE
M/S. ALEMBIC LIMITED, ALEMBIC ROAD, VADODARA - 390 003, GUJARAT, an Indian Company incorporated under the Companies Act, 1956.
The following composition and manufacturing process particularly describes and ascertains the nature of this invention, and the manner in which it is to be performed.


Title of the Invention:
A Process of Preparing Tablet Dosage Form of Azithromycin Monohydrate.
Azithromycin is the U.S.A.N. (generic name) for 9a-aza-9a-methyl-9-deoxo-9a-homoerythromycin A, a broad spectrum antimicrobial compound derived from erythromycin A. Azithromycin was independently discovered by Bright, U.S. Pat. No. 4,474,768 and Kobrehel et al., U.S. Pat. No. 4,517,359. These patents disclose that Azithromycin and certain derivatives thereof possess antibacterial properties and are accordingly useful as antibiotics. Azithromycin Monohydrate is the pseudopolymorph of various crystalline forms of Azithromycin base. Azithromycin Monohydrate is hygroscopic and therefore necessities to maintain a moisture level of 3 - 4% in the final dosage form.
This invention provides a tablet dosage form of Azithromycin Monohydrate which can be administered to a mammal (including humans). The dosage form comprises Azithromycin Monohydrate and a pharmaceutically acceptable carrier, as hereinafter further detailed and described. The dosage form is in the form of a coated tablet.
In a further aspect, this invention provides a method for treating a microbial infection in a mammal, which comprises administering, to a mammal in need of such treatment, an antimicrobially effective amount of Azithromycin Monohydrate in an tablet dosage form.

The main advantage of the invention are
1. Azithromycin Monohydrate is a pseudopolymorph of Azithromycin indicated for the treatment of patients with mild to moderate infections.
2. Tablet dosage form provides for a reproducible and accurate delivery of Azithromycin Monohydrate.
3. Tablet dosage form of Azithromycin Monohydrate will provide the durability of physical characteristics, stability of chemical and physiologic activity for extended period of storage.
4. Film coating of the tablets help mask the bitter taste of the drug during its transient residence in buccal cavity.

EXAMPLE 1:
Azithromycin Monohydrate 250 mg Tablets

S.No. Ingredients mg/ tablet
1 Azithromycin Monohydrate 277.00
2 Microcrystalline Cellulose 69.00
3 Sodium Lauryl Sulphate 5.00
4 Povidone 5.00
5 Starch 13.00
6 Croscarmellose Sodium 22.00
7 Colloidal Silicon Dioxide 4.00
8 Sodium Stearyl Fumarate 5.00
9 Hydroxypropyl Methylcellulose 8.00
10 Talc 1.00
11 Titanium dioxide 1.00
12 Polyethylene glycol 2.00
Total 412.00

Procedure (EXAMPLE 1):
1. Sift Azithromycin Monohydrate, Croscarmellose Sodium, Starch and Microcrystalline Cellulose through mesh 40 sieve using a sifter.
2. Dry blend the sifted mass of step (1) in a suitable mixer. s -3. Prepare the binder solution by dissolving Povidone in water.
4. Granulate the mass of step (2) with the binder solution of step (3) in an high shear mixer-granulator.
5. Dry the wet mass in a suitable drier and size the dried mass through a mesh 20 sieve.
6. Sift Colloidal Silicon dioxide, Sodium Lauryl Sulphate, Croscarmellose Sodium and Sodium Stearyl Fumarate through sieve of # 60 using a sifter.
7. Lubricate the dried granules of step 5 with the mass of step 6 in blender.
8. Compress the lubricated granules of step 7 into a tablet of suitable shape with an average weight of 400 mg.
9. Prepare coating solution by dispersing Talc and Titanium dioxide in water followed by addition of Hydroxypropyl Methylcellulose, stir for 45 minutes and then add Polyethylene Glycol to it.
10.Coat the core tablets of step 8 with the coating solution of step 9 in a suitable coating system, to achieve a weight gain of 12 mg per tablet.

EXAMPLE 2:
Azithromycin Monohydrate 500 mg Tablets

S.No. Ingredients mg /.tablet •,
1 Azithromycin Monohydrate 554.00
2 Lactose ^ 169.00
3 Sodium Lauryl Sulphate 7.00
4 Povidone 8.00
5 Starch 55.00
6 Croscarmellose Sodium 32.00
7 Colloidal Silicon Dioxide 15.00
8 Magnesium Stearate 10.00
9 Hydroxypropyl Methylcellulose 17.00
10 Talc 2.00
11 Titanium dioxide 2.00
12 Polyethylene glycol 3.75
13 Iron oxide Yellow 0.25
Total 875.00

Procedure (EXAMPLE 2):
1. Sift Azithromycin Monohydrate, and Lactose through mesh 40 sieve using a sifter.
2. Dry blend the sifted mass of step (1) in a suitable mixer
3. Prepare the binder solution by dissolving Povidone in water.
4. Granulate the mass of step (2) with the binder solution of step (3) in an high shear mixer-granulator.
5. Dry the wet mass in a suitable drier and size the dried mass through a mesh 20 sieve.
6. Sift Colloidal Silicon dioxide, Sodium Lauryl Sulphate, Starch, Croscarmellose Sodium and Magnesium stearate through sieve of # 40 using a sifter.
7. Lubricate the dried granules of step 5 with the mass of step 6 in blender.
8. Compress the lubricated granules of step 7 into a tablet of suitable shape with an average weight of 850 mg.
9. Prepare coating solution by dispersing Talc, Iron oxide Yellow and Titanium dioxide in water followed by addition of Hydroxypropyl Methylcellulose, stir for 45 minutes and then add Polyethylene Glycol to it.
10. Coat the core tablets of step 8 with the coating solution of step 9 in a suitable coating system, to achieve a approximate weight gain of 25 mg per tablet.

Test reports

Sr.No. Parameters TEST RESULTS5'
Example 1 Example 2
1 Description White to off white, film coated tablets. Yellow colored, film coated tablets.
2 Disintegration time filled capsule 7 - 8 Minutes 8-10 Minutes
3 Average weight 415.30 mg 879.50 mg
4 Hardness 8 Kg/cm2 10 Kg/cm2
5 Assay 101.55 %w/w 99.55 % w/w

A PROCESS OF PREPARING TABLET DOSAGE FORM OF AZITHROMYCIN MONOHYDRATE
What we claim :
1. A process for preparation of Azithromycin Monohydrate Tablets
comprising of the following steps,
a. Sift Azithromycin Monohydrate, Croscarmellose Sodium,
Microcrystalline Cellulose and Starch through sieve of mesh 40.
b. Mix the sifted mass of step (a) in a suitable mixer.
c. Prepare the binder solution by dissolving Povidone in water.
d. Granulate the mass of step (b) with the solution of step (c).
e. Dry the mass of step (d) in a suitable drier and size the dried mass
through sieve of mesh 20.
f. Sift Croscarmellose Sodium, Starch, Sodium Lauryl Sulphate,
Colloidal silicon dioxide and Sodium Stearyl Fumarate through sieve
of mesh 40.
g. Lubricate the dried granules of step (e) with the sifted mass of step (f)
in a suitable blender.
h. Compress the mass of step (g) into a tablet of suitable shape.
i. Prepare coating solution by dispersing Hydroxypropyl
Methylcellulose in water with stirring. To it add Talc, Titanium dioxide, Color and Polyethylene Glycol. Pass the prepared coating solution through colloid mill.
j. Coat the core tablets of step (h) with the coating solution of step (i).
2. The dosage form of claim 1, wherein the quantity of Azithromycin Monohydrate is equivalent to Azithromycin base in the range 125 to 600 mg.
3. The core tablet of claim 3, wherein the Active pharmaceutical ingredient is in the range of 40 % to 80 % w/w, Microcrystalline Cellulose is in the range of 0 % to 58 % w/w, Starch is in the range of 0 to 58 % w/w, Binder (Povidone) is in the range of 0.1 % to 10 % w/w, Wetting agent (Sodium lauryl sulphate) is in the range of 0.1 % to 5 % w/w, Disintegrating agent (Croscarmellose Sodium) is in the range of 1% to 10 % w/w, Glidant (Colloidal Silicon Dioxide) is in the range of 0.1 % to 5

% w/w and lubricant (Sodium Stearyl Fumarate| is in the range of 0.1 %
to 5 % w/w.
4. The dosage form of claim 1, wherein the core tablet is coated with the aqueous dispersion of Hydroxypropyl Methylcellulose to achieve a weight gain of 1 to 5 % w/w of the core tablet weight.
5. A process of preparation of Azithromycin Monohydrate tablets as per claim 1 wherein the Microcrystalline Cellulose may be replaced with Lactose in the range of 0 % to 58 % w/w of the tablet weight.
6. A process of preparation of Azithromycin Monohydrate tablets as per claim 1 wherein the Sodium Stearyl Fumarate may be replaced with Magnesium stearate in the range of 0.1 % to 5 % w/w of the tablet weight.