Azithromycin 500 Tablets IP
Azithromycin 500 Tablet is an antibiotic used to treat various types of bacterial infections of the respiratory tract, ear, nose, throat, lungs, skin, and eyes in adults and children. It is also effective in typhoid fever and some sexually transmitted diseases like gonorrhea.
Azithromycin 500 Tablet is taken orally, preferably one hour before or 2 hours after a meal. It should be used regularly at evenly spaced time intervals as prescribed by your doctor. Do not skip any doses and finish the full course of treatment even if you feel better. Stopping the medicine too early may lead to the return or worsening of the infection.
Commonly seen side effects with Azithromycin 500 tablet include vomiting, nausea, stomach pain, and diarrhea. These are usually temporary and subside with the completion of treatment. Consult your doctor if you find these side effects worry you or persist for a longer duration.
Uses of Azithromycin 500 mg Tablets
Treats mild to moderate susceptible infections caused by bacteria and other micro-organisms which include chest, throat, and nasal infections (such as bronchitis, pneumonia, tonsillitis, sore throat, and sinusitis)
Treats ear infections and skin & soft tissue infections (such as an abscess/boil) in affected individuals
Treats sexually transmitted diseases such as cervicitis (caused by organisms such as Chlamydia trachomatis/ Neisseria gonorrhea) in affected individuals
HOW AZITHROMYCIN 500 TABLET WORKS
Azithromycin 500 mg Tablets works by inhibiting bacterial protein synthesis (essential for the bacteria to grow) that results in its destruction thus preventing its growth and spread of infection in affected individuals.
DIRECTIONS FOR USE
Take Azithromycin 500 mg Tablets as advised by your physician. Swallow the medicine with a glass of water. Do not crush or chew the medicine. Your doctor will decide the correct dose and duration for you depending on your age, body weight, and disease condition.
Manufacturing Procedure of Azithromycin 500 mg Tablets
TABLE OF CONTENTS
- PRODUCT DETAILS
- MANUFACTURING FORMULA
- LIST OF EQUIPMENT
- GENERAL PRECAUTIONS
- MANUFACTURING INSTRUCTIONS
- MANUFACTURING PROCESS DETAILS
- GRANULATION
- COMPRESSION
- COATING
PRODUCT DETAILS:
Product Name:
Azithromycin Tablets IP
Product Description:
White color elongated biconvex, film-coated tablet having one side mid-break line and the other side plain
Strength: 500 mg
Label claim:
Each film-coated tablet contains:
Azithromycin Dihydrate IP
equivalent to Azithromycin Anhydrous – 500 mg
Batch Size: 2,00,000 Tablets
Average Weight: 714 mg
Shelf Life: 24 months
Storage: Store in a cool, dry, and dark place below 250C
Drug Category: Macrolide Antibiotics
MANUFACTURING FORMULA:
| Material Name | Category | Overages | Batch Qty. |
| Dry Mixing | |||
| Azithromycin IP | API | 5 % | 105.000 kg |
| MCCP Plain IP | Diluent | —- | 10.000 kg |
| Binder | |||
| PVPK-30 IP | Binder | —- | 0.800 kg |
| Sodium Benzoate IP | Preservative | —- | 0.280 kg |
| Sodium Starch Glycolate IP | Binder | —- | 4.000 kg |
| Purified Water IP | Diluent | —- | 52.000 liter |
| Lubricants | |||
| Talcum IP | Anti-caking agent | —- | 2.800 kg |
| MCCP PH-102 IP | Diluent | —- | 10.920 kg |
| Cross Carmillose Sodium IP | Disintegrant | —- | 2.800 kg |
| Crospovidone XL IP | Disintegrant | —- | 1.400 kg |
| Aerosil IP | Glidant | —- | 0.600 kg |
| Calcium Stearate IP | Anti-Adherent | —- | 1.400 kg |
LIST OF EQUIPMENT:
Weighing Balance
Vibro Sifter
Paste Kettle with stirrer
Portable Stirrer
Multi Mill (screen size 2 mm and 8 mm)
Rapid Mixer Granulator (RMG)
Fluid Bed Dryer (FBD)
Double Cone Blender
Halogen Moisture Balance
Compression Machine
GENERAL PRECAUTIONS:
API Description: A white or almost white color powder. Protected from moisture during storage.
All the Manufacturing Activities shall be performed under controlled conditions (temperature NMT 250C and relative humidity NMT 60%).
When working with Active Ingredients and drug products or a mixture of Active Ingredients and Excipients, wear gloves and a mask to avoid exposure and contact with any body parts.
MANUFACTURING INSTRUCTIONS:
All activities shall be performed as per current SOPs.
Take the line clearance from QA before starting the manufacturing operation during batch-to-batch and product-to-product changeover.
Do not overwrite any entry. In case of a mistake, cancel the entry by a single line with a sign & date and make the correct entry.
MANUFACTURING PROCESS DETAILS:
GRANULATION:
STEP – I (SIFTING):
Check Sieve Integrity (before sifting and after sifting).
Set the Vibro Sifter and sieve the Dispensed Materials as per the Sieve Sizes mentioned below:
| Material Name | Std. Qty. (kg) | Sieve No. |
| Dry Mixing | ||
| Azithromycin IP | 105.000 kg | 18 # |
| MCCP Plain IP | 10.000 kg | 60 # |
| Binder | ||
| PVPK-30 IP | 0.800 kg | 20 # |
| Sodium Benzoate IP | 0.280 kg | 20 # |
| Sodium Starch Glycolate IP | 4.000 kg | 60 # |
| Lubricant | ||
| Talcum IP | 2.800 kg | 60 # |
| MCCP PH-102 IP | 10.920 kg | 40 # |
| Cross Carmillose Sodium IP | 2.800 kg | 60 # |
| Crospovidone XL | 1.400 kg | 60 # |
| Aerosil IP | 0.600 kg | 14 # |
| Calcium Stearate IP | 1.400 kg | 60 # |
After sifting divide the sifted Azithromycin IP (105.000 kg) in two equal parts for LOT-I and LOT-II (52.500 kg each) and collect in two Poly-lined HDPE Containers (capacity: 65 liter each).
After sifting divide the sifted MCCP Plain IP (10.000 kg) into two equal parts for LOT-I and LOT-II (5.000 kg each) and collect in two above Poly-lined HDPE Containers (capacity: 65 liters each) with Azithromycin.
Collect sifted PVPK-30 IP (0.800 kg) in one Polybag (capacity: 1.0 kg).
Collect sifted Sodium Benzoate IP (0.280 kg) in one Polybag (capacity: 1.0 kg).
Collect sifted Sodium Starch Glycolate IP (4.000 kg) in one Polybag (capacity: 5 kg)
Collect the sifted Talcum IP (2.800 kg), MCCP PH-102 IP (10.920 kg), Cross Carmillose Sodium IP (2.800 kg), Crospovidone XL (1.400 kg), and Aerosil IP (0.600 kg) in one Polybag (capacity: 20 kg)
Collect sifted Calcium Stearate IP (1.400 kg) in Polybag (capacity: 2.0 kg).
STEP – II (BINDER PREPARATION): FOR LOT-I and LOT-II:
Take purified water (42.00 liters) in Paste Kettle (capacity: 100 liters), heat the purified water to 350
Take purified water (5.000 liter, at temperature 350C) from the Paste Kettle of Step-II (a) in SS Container (capacity: 10 liter) and add sifted Sodium Benzoate IP (0.280 kg) and PVPK-30 IP (0.800 kg) and mix one by one with stirrer till dissolved properly in water and make a solution.
Heat the remaining purified water to 800C of Step-II (a) (37.000 liters) in a Paste Kettle.
Take purified water separately (10.000 liters, at room temperature) in an SS Container (capacity: 20 liter) and add Sodium Starch Glycolate IP (4.000 kg) slowly continuously stirring till a uniform solution is ready.
Add the above solution of Step-II (d) to the heated purified water of Step–II (c) in a Paste Kettle with continuous stirring till uniform paste is ready.
(f) Add Step -II (b) solution with continuous stirring to Step II (c) till the final paste is ready.
(g) Transfer the ready paste by tilting the Paste Kettle in one SS Container (capacity: 100 liters). Cool the paste up to 35°C to 40°C.
(h) Divide paste (Qty.57.080 kg) into two equal parts (Qty. 28.540 kg each) for LOT- I and LOT- II SS Containers (capacity: 70 liters each).
STEP – III (DRY MIXING): FOR LOT-I:
Transfer the sifted Azithromycin IP and MCCP Plain IP in Rapid Mixer Granulator (capacity: 160 liters) running at a slow speed impeller and dry mix the materials till uniform mixing.
Mixing Time: 05 minutes.
Mixing Speed: 05 minutes at slow speed.
Ampere Load of Impeller: _________ ampere (To be validated in next batch).
STEP –IV (BINDING OF DRY MIX MATERIAL): FOR LOT- I:
Slowly add the binder of Step – II to dry mix materials of Step – III in Rapid Mixer Granulator running at a slow speed impeller for 5 minutes till binder addition. After binder addition run the impeller and chopper both at slow speed for 08 min and finally run both chopper and impeller at fast speed for 02 minutes till uniform mixing. Unload the material in SS Container (capacity: 100 liters) from RMG by opening the discharge point with a running impeller.
Mixing Time: 15 minutes.
Ampere Load of Impeller: 0.62 to 1.02 ampere. (To be validated in next batch).
STEP-V (WET SCREENING) FOR LOT – I:
Check Screen Integrity (before and after screening).
Take wet material from SS Container and pass through Multi-Mill with screen size 8 mm and collect the wet material in SS Container (capacity: 100 liters) and after screening transfer the wet material in an FBD bowl.
STEP –VI (DRYING): FOR LOT –I:
Dry the wet material of Step-V in FBD (capacity: 120 kg) until the LOD of granules is achieved between 1.0 to 1.5 % at 105°C checking by Halogen Moisture Balance and after drying unload the material in two Poly-lined HDPE Container (capacity : 45 liter each).
Inlet Temperature: 60°C. (To be validated in next batch).
Outlet Temperature: To be established.
Raking Frequency: After 30 minutes.
Drying Time: 02 hours. (To be validated in next batch).
STEP-VII (SIZING/MILLING): FOR LOT-I:
Check Sieve & Screen Integrity (before and after sifting & screening).
Set the Vibro Sifter and fix the Sieve 18 # and sieve the dried material of Step-VI and collect in three Poly-lined HDPE Containers (capacity: 45 liter each) and remaining retention after sieving, pass through the Multi-Mill using screen size 2 mm. After screening keep the screened material with sized material in the above Poly-lined HDPE Containers. Weigh and record the sized/milled granules quantity.
Blade Type: Both (Knife blades and Scraping blades).
Rotor Speed: 2000 RPM.
NOTE:
FOR LOT – II: Please follow the same procedure as LOT – I of dry mixing, binding of dry mix material, wet screening, drying, and sizing/ milling.
STEP – VIII (PRE –LUBRICATION):
Load the sized granules of Step-VII of LOT-I and LOT-II in Double Cone Blender (capacity: 400 liters) and add sifted Talcum IP, MCCP PH-102 IP, Cross Carmillose Sodium IP, Crospovidone XL, Aerosil IP, mix properly till uniform mixing of sized material with Pre-Lubricating Materials.
Mixing Time: 30 minutes (15 minutes clockwise direction and 15 minutes anti-clockwise direction).
Mixing Speed: 10 RPM.
STEP – IX (LUBRICATION):
Add the sifted Calcium Stearate IP in Pre- Lubricated Materials of Step-VIII and mix properly till uniform mixing of materials with Calcium Stearate IP.
Mixing Time: 05 minutes. (Clockwise direction).
Mixing Speed: 10 RPM.
STEP- X (BLEND SAMPLE ANALYSIS):
After completion of lubrication, collect the composite blend sample (Qty. 10 gm) and send to QC for analysis according to the table below:
Test: Specification
The appearance of the blend: White color free-flowing granular powder
Blend Uniformity:90 % to 110 %
Blend Assay:98 % to 103 %
LOD:1.0 % to 1.5 %
STEP – X:
Take the Tare Weight of four Poly-lined HDPE Containers (capacity: 45 liters each), record the Tare Weight in BMR and unload the above-blended material from Double Cone Blender in Poly-lined HDPE Containers (capacity: 45 liters each) and weigh the material with containers and record the Gross Weight of the material and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
Affix the status label with the following details – Product Name, Batch No., Batch Size, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Container.
Batch Yield of Lubricated granules:
Theoretical Batch Yield: 140.00 kg (100 %)
Actual Batch Yield Limit NLT 138.600 kg (NLT 99 %) (To be established in next batch)
STEP – XI:
Clean all equipments used in the granulation as per respective equipment cleaning SOP.
COMPRESSION:
STEP – I:
After receiving of QC approval for the blend, verify the Net Weight of the received blend as per the status label in Granules Day Store.
After confirmation continue the compression with 27 stations (D-Tooling) Compression Machine of the blend as per the following parameters and In Process checks under controlled environmental conditions.
| Parameters | Standard | In-Process Frequency |
| Machine Speed | 15 RPM to 18 RPM | —– |
| Upper Punch Size | 17.5 mm x 8.0 mm with break line | —– |
| Lower Punch Size | 17.5 mm x 8.0 mm | —– |
| Length of Tablets | 17.5 mm | —– |
| Width of Tablets | 8.0 mm | 2 hours |
| Thickness of Tablets | 5.6 mm ±.2 mm | 2 hours |
| Weight of 20 Tablets | 14.000 gm. ± 2% | 30 minutes |
| Tablets for Dissolution | 700 mg ± 2% | —– |
| Dissolution | NLT 80 % | —– |
| Product Description | White color elongated, biconvex, uncoated tablet having one side mid-break line and the other side plain | 30 minutes |
| Uniformity of Weight | NMT 02 tablets out of 20 deviate from the standard average weight by more than 3 % and no single tablet deviates from the standard average weight by more than 5 % | 01 hour |
| Standard Average Weight of Tablets | 700 mg ± 2 % | 30 minutes |
| Hardness | NLT 4 kg/cm2 | 30 minutes |
| Disintegration Time | NMT 15 min | 01 hour |
| Friability | NMT 1% | 01 hour |
Collect the compressed tablets in SS Container (capacity: 20 liters each on both sides), when SS containers are filled with tablets, transfer the tablets to four Poly-lined HDPE Containers as given in below Step-III.
STEP – II:
Send the composite sample of compressed tablets (Qty. 30 tablets) to QC department for analysis.
STEP – III:
Take Tare Weight of four Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and transfer the compressed tablets in Poly-lined HDPE Containers (capacity: 45 liter each) and weigh the compressed tablets with containers and record the Gross Weight of the compressed tablets and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Container.
Batch Yield of Compressed Tablets:
Theoretical Batch Yield: 140.00 kg (100 %)
Actual Batch Yield Limit NLT 138.600 kg (NLT 99 %) (To be established in next batch)
STEP – IV:
After completion of compression clean the Compression Machine as per cleaning SOP.
COATING:
Verify the Net Weight of the received compressed tablets for coating as per the status label and after confirmation continues for tablet coating.
STEP – I (COATING MATERIALS DETAILS):
Material Name:
Instacoat White Aq.III: 2.800 kg.
Purified Water IP:16.800 liter
STEP-II (LIST OF EQUIPMENT FOR COATING):
| Sr. No. | Machineries/Equipment |
| 1. | Coating Pan and Coating Machine (42″) |
| 2. | Spray Gun (02) |
| 3. | Filter Cloth 100 # |
| 4. | Portable Stirrer |
| 5. | SS Containers |
| 6. | Poly-lined HDPE Containers with lid |
STEP – III (PREPARATION OF COATING SOLUTION): FOR LOT-I & LOT-II:
Take Purified Water IP (16.800 liter, at room temperature) in SS Container (capacity: 20 liter) and add Instacoat White Aq.III (2.800 kg and mix together by Portable Stirrer continuously stirring till uniform mixing achieved.
Speed of stirrer: Constant.
Mixing Time: 15 minutes.
Filter the coating solution with Filter Cloth 100 # in one SS Container (capacity: 20 liter).
Keep the solution for 15 minutes to let the foam settled down. Thereafter proceed with the coating process.
Divide the coating solution equally into two parts for LOT – I and LOT – II in SS Container (capacity: 15 liter each).
STEP – IV (COATING PROCEDURE): FOR LOT-I:
The coating will be done in two lots, dividing the total compressed tablets into two equal quantities for LOT -I and LOT -II (70.000 kg tablets for each lot).
Load the tablets in the coating pan (Capacity: 42″), start the hot air blower, set the inlet air temperature at 60°C to 65°C and start the exhaust fan & warm the tablets bed 40°C to 45°C.
After warming the tablets, take weight of 100 warmed tablets and record the weight in BMR for calculation of weight buildup of tablets after coating.
Set the coating parameter as given in below table and start the coating process by starting coating spray through gun.
| Parameter | Specification |
| No. of Baffles in coating pan | 06 |
| No. of Guns | 02 |
| Inlet Temperature | 60°C to 65°C (To be validated in the next batch) |
| Peristaltic Pump Speed | 2- 4 RPM (To be validated in the next batch) |
| Atomization | 2.5 to 3.0 kg/cm2 |
| Gun to Tablet Bed Distance | 8 inch |
| BED Temperature | 400C to 45 0C (To be validated in the next batch) |
| Pan RPM | 13 to 15 RPM |
| % Weight Gain | 1.5 to 2.0 % |
| Coating Time | 2-3 Hours each (To be validated in the next batch) |
NOTE:
FOR LOT – II (COATING PROCEDURE):
Please follow the same procedure of LOT – I of coating from Step IV.
STEP – V (COATING IN-PROCESS CHECK PARAMETERS):
After completion of coating perform the In Process checks as per the below parameters:
| Parameters | Standard |
| Product Description | White color elongated, biconvex, film-coated tablet having one side mid-break line and the other side plain |
| Weight of 20 Tablets
after coating |
14.280 gm. ± 2 % |
| Average Weight after coating | 714 ± 2% |
| Individual Tablets Weight Variation | ± 3% |
| Thickness | 5.61 mm ± 0.2 mm |
| Disintegration | NMT 30 min. |
STEP – VI:
Send the composite sample of coated tablets (Qty. 30 tablets of each Lot) to QC department for analysis.
STEP – VII:
Take Tare Weight of four Poly-lined HDPE Containers (capacity: 45 liter each), record the Tare Weight in BMR and transfer the coated tablets in Poly-lined HDPE Containers (capacity: 45 liter each) and weigh the coated tablets with containers and record the Gross Weight of the coated tablets and calculate the Net Weight of the material as per given formula:
Net Weight = Gross Weight – Tare weight
Affix the status label with following details – Product Name, Batch No., Batch Size, Avg. Weight, Mfg. Date, Exp. Date, Tare Weight, Gross Weight and Net Weight on the Poly-lined HDPE Containers.
Batch Yield of Coated Tablets:
Theoretical Batch Yield: 140.00 kg (100 %)
Actual Batch Yield Limit NLT 138.600 kg (NLT 99 %) (To be established in next batch).
Blister Packing:
Shift the inspected tablets to the blister section and blister pack them using the Triple Track Blister Packing Machine by operating it.
IN-PROCESS CONTROLS:
The following in-process controls should be maintained during the processing:
Check Raw materials used for manufacturing purposes are all approved materials and have ‘Released’ labels fixed on them.
All weighed Raw materials should be counter-checked by the Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of the Production and QC/QA Manager.
Physical characteristics of Raw materials like color, odor, and consistency are checked before compounding.
Humidity and temperature should be maintained during the compression of thermolabile products.
A sample of dried granules should be sent to the Quality Control Department for the determination of Moisture content.
The total weight of blended powder should be checked in the presence of the Manufacturing Chemist and recorded the same in the Batch Manufacturing Record.
Bulk samples should be sent for analysis to the Quality Control Department before starting the compression of tablets.
Weight Variation: I) Intermittently weight variation of compressed tablets should be checked at 30 minutes intervals by the Assistant Manufacturing Chemist and a record for the same should be kept in the Batch Manufacturing Record
Out-of-limit tablets should be checked by the Weight Variation Method.
Take the average weight of 20 tablets on the calibrated balance and calculate the upper and lower limit as per below by IP/BP/USP:
Take the weight of individual tablets and check if all the tablets are lying within the limits.
Select the tablets only if no more than two tablets are out of the percentage limit and if no tablet differs by more than two times the percentage limit, otherwise reject the tablets.
Adjust the desired weight of the tablets in the Compression Machine by moving the weight adjustment cam clockwise or anticlockwise accordingly as per the Standard Operating Procedure of the Compression Machine.
Re-check the weight of tablets for further adjustment, if any.
The thickness of Tablets: The thickness of the tablets should be determined using the vernier caliper. The thickness of the tablet should be checked whenever weight adjustments are made.
Hardness of the tablets: The equipment used is the ‘Monsanto’ type hardness tester. The hardness of the compressed tablets should be checked at regular intervals to determine the need for pressure adjustments on the tableting machine.
The hardness of tablets varies between 2-4 Kg/cm2.
Friability:
Roche Friabilator is used for measuring the Friability. The instrument is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling, and shipping.
Adjust the instrument to 25 RPM before adding the tablets.
Weigh 20 Tablets on a calibrated balance. Transfer the tablets to the plastic chamber. Close the drum tightly.
Switch on the apparatus. Operate the Friabilator for 100 revolutions.
De-dust and reweigh the tablets. Loss in weight indicates the ability of tablets to withstand wear.
Take 10 tablets to check the friability, when the average weight of the tablet is 1g or more than 1g.
Friability Limit = Less than 1.0%
Disintegration Test:
Disintegration is the time required for the group of tablets to disintegrate into the particles. Disintegration Test should be carried out at regular intervals of 1 hour by using the Disintegration Test Apparatus.
The tube assembly unit is removed from the glass beaker and from each tube the plastic discs are removed.
Place the tablets in each of the 6 tubes along with a plastic disc over the tablets.
The glass beaker is filled with water. The water in the beaker is retained at the temperature of 37+1˚C throughout the test by suitably setting the thermostat.
Introduce a tube assembly unit into a glass beaker in such a way that the wire mesh at the base of each tube is at least 2.5cm below the surface of the liquid when the basket is at its highest position.
Switch on the apparatus to move the basket assembly containing the tablets up and down through a distance of 5 to 6 cm at a frequency of 28 to 32 cycles per minute. Start the stopwatch.
When the tablets have disintegrated i.e. when no particles remain on the wire mesh at the bottom of the tube, stop the stopwatch. Note the time taken for the disintegration of the tablets and record the same in the Batch Manufacturing Record.
If one or two tablets fail to disintegrate, the test is to be repeated using 12 tablets
Disintegration Time of uncoated tablets= Not more than 15 minutes
Disintegration Time of coated tablets= Not more than 30 minutes
Tablets taken for testing and In-process control should not be added to the bulk batch to avoid mix-ups and cross-contamination.
Inspection and sorting of rejected tablets should be done.
The strips and cartons should be checked thoroughly for proper batch coding.
The Manufacturing Chemist and Production should randomly check that the correct no. of strips are being packed in each carton and also the number of cartons in each shipper is the same as that shown in the proof.
Intimation should be sent to the Quality Control Department for finished product sampling and testing.
After the completion of labeling and packaging, the coded cartons should be accounted for, and rejected printed material should be destroyed in the presence of the QC/QA Manager. Fill out the destruction sheet and attach the same in the Batch Manufacturing Record.
It will be ensured that filling or packaging equipment has been properly cleaned after the completion of the batch.
Filling or packaging of the next product should not commence until the IPQA has given the ‘Line Clearance’