THE PATENTS ACT, 1970 (39 of 1970)
COMPLETE SPECIFICATION
A PROCESS OF PREPARING CAPSULE 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 Capsule 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 capsule 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 hard gelatin capsule.
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 capsule dosage form.

The main advantage of the invention are'
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1. Azithromycin Monohydrate is a pseudopolymorph of Azithromycin base indicated for the treatment of patients with mild to moderate infections.
2. Capsule dosage form of azithromycin monohydrate will provide for precision of dosage and convenience of administration.
3. Capsule dosage form will provide for durability of physical characteristic and stability of chemical and physicologic activity of Azithromycin Monohydrate for extended period of storage.
4. Capsule dosage form of Azithromycin Monohydrate will have elegance, ease of use, portability and easy to swallow due to its smooth and slippery shell.
5. Capsule dosage form of Azithromycin Monohydrate will be tasteless, so no additional processing for the taste masking or film coating is desired.
6. The cost of manufacturing is relatively very low compared to taste masked dosage forms, including taste masking at drug particle level or the film coating of the dosage form.
7. Simple manufacturing process.
8. Cost effective due to less processing and less pharmaceutical aids (Excepients) required in the manufacturing.

EXAMPLE 1:
Azithromycin Monohydrate 250 mg Capsules

S.No. Ingredients mg / capsule
1 Azithromycin Monohydrate 277.00
2 Dibasic Calcium Phosphate dihydrate 23.00
3 Sodium Lauryl Sulphate 3.00
4 Croscarmellose Sodium 19.00
5 Magnesium Stearate 3.00
Total 325.00
Procedure (EXAMPLE 1):
1. Sift Azithromycin Monohydrate and Dibasic Calcium Phosphate dihydrate through # 40 sieve using a sifter.
2. Dry blend the sifted mass of step (1) in blender for 30 minutes.
3. Sift Sodium Lauryl Sulphate, Croscarmellose Sodium and Magnesium Stearate through sieve of # 60 using a sifter.
4. Lubricate the blend of step 2 with the mass of step 3 in blender.
5. Fill the lubricated mass of step 4 into hard gelatin capsules of size '1' using a suitable capsule filling machine.

EXAMPLE 2:
Azithromycin Monohydrate 500 mg Capsules

S.No. Ingredients mg / capsule
1 Azithromycin Monohydrate 554.00
2 Dibasic Calcium Phosphate dihydrate 10.00
3 Sodium Lauryl Sulphate 6.00
4 Croscarmellose Sodium 24.00
5 Magnesium Stearate 6.00
Total 600.00
Procedure (EXAMPLE 2):
1. Sift Azithromycin Monohydrate and Dibasic Calcium Phosphate dihydrate through # 40 sieve using a sifter.
2. Dry blend the sifted mass of step (1) in blender for 45 minutes.
3. Sift Sodium Lauryl Sulphate, Cross Carmellose Sodium and Magnesium Stearate through sieve of # 60 using a sifter.
4. Lubricate the blend of step 2 with the mass of step 3 in blender.
5. Fill the lubricated mass of step 4 into hard gelatin capsules of size '00' using a suitable capsule filling machine.

Test reports

Sr.
No. Parameters TEST RESULTS
Example 1 Example 2 .
1 Description of blend White to off white colored blend, moderate in flow. White to off white colored blend, moderate in flow.
2 Disintegration time filled capsule 10-12 Minutes 12-14 Minutes
3 Average Net Content 327.10 mg 605.50 mg
4 Assay 99.73 % w/w 102.11 %w/w

A PROCESS OF PREPARING CAPSULE DOSAGE FORM OF AZITHROMYCIN MONOHYDRATE
What we claim :
1. A process for preparation of Azithromycin Monohydrate Capsules
comprising of the following steps,
a. Sift Azithromycin Monohydrate and Dibasic Calcium Phosphate
dihydrate through sieve of mesh 40.
b. Dry blend the sifted mass of step (a) in a suitable blender.
c. Sift Sodium Lauryl Sulphate, Magnesium Stearate and
Croscarmellose Sodium through sieve of mesh 60.
d. Lubricate the blend of step (b) with the sifted mass of step (c) in a
blender.
e. Fill the lubricated blend of step (d) into hard gelatin capsules of
suitable size using a suitable capsule filling machine.
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 dosage form of claim 2, wherein the active pharmaceutical ingredient is in the range of 70 % to 98 % w/w, Dibasic Calcium Phosphate dihydrate is in the range of 0 % to 29 % w/w, Wetting agent (Sodium lauryl sulphate) is in the range of 0.1 % to 5 % w/w, Disintegrating agent (Cross Carmellose Sodium) is in the range of 1% to 10 % w/w and lubricant (Magnesium Stearate) is in the range of 0.1 % to 5 % w/w.
4. A process of preparation of Azithromycin Monohydrate capsules as per claim 1(a) wherein Azithromycin Monohydrate may be replaced with compacted Azithromycin Monohydrate.
5. A process of preparation of Azithromycin Monohydrate capsules as per claim 1(a) wherein Azithromycin Monohydrate may be replaced with granulated Azithromycin Monohydrate.

6. A process of preparation of Azithromycin Monohydrate capsules as claim 1 (a) wherein Dibasic Calcium Phosphate dihydrate may be replaced with Lactose in the range 0 % to 29 % w/w
Dated this 9tn day of July, 2003 Applicant for the Organization

Shri Sampad Bhattacharya (Vice President - Technical)