Metformin Hydrochloride Tablet 500 mg: A Comprehensive Guide
Metformin hydrochloride is a widely prescribed medication used to manage type 2 diabetes mellitus. It belongs to the class of drugs known as biguanides and is known for its effectiveness in controlling blood glucose levels. Metformin hydrochloride tablets in the 500 mg strength are commonly prescribed due to their optimal dosage for many patients. We will explore various aspects of Metformin Hydrochloride Tablet 500 mg, including its uses, mechanism of action, dosage, potential side effects, precautions, and other essential information to help you better understand this commonly prescribed medication.
Overview of Metformin Hydrochloride
Introduction to Metformin:
Metformin is an oral antidiabetic medication used to control blood glucose levels in individuals with type 2 diabetes. It is considered a first-line therapy due to its efficacy, safety, and affordability.
Mechanism of Action:
Metformin works primarily by reducing the amount of glucose produced by the liver and enhancing insulin sensitivity in muscle and adipose tissues. It does not stimulate insulin secretion from the pancreas.
Indications:
Metformin Hydrochloride Tablet 500 mg is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
Usage and Dosage
The usual starting dose of Metformin Hydrochloride Tablet 500 mg is 500 mg once or twice daily, with the dosage adjusted gradually based on individual response and blood glucose levels. The maximum daily dose typically ranges from 1,500 mg to 2,550 mg.
Administration and Timing:
Metformin Hydrochloride Tablet 500 mg is usually taken orally with meals to reduce gastrointestinal side effects. It is important to follow the prescribed dosage and administration instructions provided by the healthcare professional.
Special Populations:
Specific considerations exist for certain patient populations, such as individuals with renal impairment, hepatic impairment, or the elderly. Adjustments to the dosage or frequency of administration may be necessary in these cases.
III. Efficacy and Safety
Efficacy of Metformin Hydrochloride:
Metformin has been extensively studied and has consistently demonstrated its effectiveness in improving glycemic control in patients with type 2 diabetes. It is associated with a reduction in HbA1c levels, fasting plasma glucose, and postprandial glucose levels.
Common Side Effects:
Metformin is generally well-tolerated, but some individuals may experience gastrointestinal side effects, such as nausea, vomiting, diarrhea, or abdominal discomfort. These side effects are usually transient and can be minimized by taking the medication with food.
Rare Side Effects and Adverse Reactions:
Although rare, some individuals may experience more serious side effects, such as lactic acidosis, a rare but potentially life-threatening condition associated with metformin use. Other rare adverse reactions include vitamin B12 deficiency, anemia, and hepatotoxicity.
Drug Interactions:
Metformin can interact with certain medications, including cimetidine, digoxin, and drugs that affect renal function. Healthcare professionals should be aware of potential drug interactions and adjust doses accordingly.
Precautions and Contraindications
Precautions for Use:
Metformin should be used with caution in patients with renal impairment, hepatic impairment, congestive heart failure, or a history of lactic acidosis. Regular monitoring of renal function and other relevant parameters is recommended.
Contraindications:
Metformin is contraindicated in patients with severe renal impairment, acute or chronic metabolic acidosis, diabetic ketoacidosis, or hypersensitivity to metformin.
Special Considerations:
Special considerations should be given to patients undergoing radiological studies using iodinated contrast agents or those scheduled for surgery under general anesthesia. Metformin should be temporarily discontinued in these situations to reduce the risk of lactic acidosis.
Monitoring and Follow-up
Monitoring Parameters:
Regular monitoring of renal function, liver function, vitamin B12 levels, and HbA1c is recommended during metformin therapy. These parameters help assess the medication’s efficacy and detect any potential adverse effects.
Follow-up with Healthcare Provider:
Patients taking Metformin Hydrochloride Tablet 500 mg should have regular follow-up appointments with their healthcare provider to evaluate the response to treatment, adjust the dosage if necessary, and address any concerns or questions.
Conclusion
Metformin Hydrochloride Tablet 500 mg is a widely prescribed medication for the management of type 2 diabetes mellitus. As an effective and well-tolerated oral antidiabetic agent, it plays a crucial role in controlling blood glucose levels and improving glycemic control. However, like any medication, Metformin Hydrochloride has specific usage guidelines, potential side effects, precautions, and contraindications that need to be considered. Adherence to proper dosage, regular monitoring, and communication with healthcare professionals are essential for optimal outcomes and the safe use of this medication. If you have any questions or concerns regarding the use of Metformin Hydrochloride Tablet 500 mg, consult your healthcare provider for personalized advice and guidance.
Master formula record (MFR)
PURPOSE: This Master formula record (MFR) is written to describe the formulae, manufacturing procedure, specifications, packing details of dosage form.
SCOPE: This MFR is performed and is applied during the manufacturing of dosage form.
RESPONSIBILITY / ACCOUNTABILITY: It is the responsibility of Manufacturing Chemist to follow and adhere to this SOP. The Production Pharmacist, QC/QA Manager and cGMP Administrator are accountable for the strict adherence to the master formula.
PRODUCT NAME: Metformin Hydrochloride Tablet
DOSAGE FORM: TABLET
BATCH SIZE: 100000
EXPIRY DATE: AFTER 27 MONTHS FROM THE DATE OF MANUFACTURING
COMPOSITION:
Each uncoated Tablet contains:
Metformin Hydrochloride U.S.P. 500mg
EQUIPMENTS TO BE USED:
Steam Jacketed Starch Paste Preparation Tank
Sifter Machine
Roto Cube Blender
Rapid Mixer Granulator
Multi Mill
Fluidized Bed Drier
Oscillating Granulator
Sifter Machine
Roto Cube Blender
Tablet Compression Machine 27 Stations
Dedusting Machine
Tablet Inspection Machine
RAW MATERIALS: –
INGREDIENTS
Metformin Hydrochloride :250.00kgs.
D.C.P.:40.000 kgs
Lactose 10.0 kg
Magnesium Stearate 1.5 kg
Aerosil 1.0 g
Starch 10.0 kg
Starch 5.0 kg
Sodium Benzoate 5.0 kg
PVPK-30 15.0 kg
Talcum 4.0 kg
PACKING MATERIALS:-
ADHESIVE TAPE ROLL BROWN
METFORMIN HCL- 500 STICKER LABEL
PLASTIC CONTAINER
CORRUGATED BOX
MANUFACTURING SPECIFICATION:
Moisture content of powder should be less than 2.0 %.
Average weight of each Tablet 190 mg. Weight Variation Limit for average weight of 20 tablets is + 5 %.
Friability limit for 10 Tablets is not more than 1.0 %.
Hardness of the Tablets varies between 2-4 kg/cm2.
Disintegration time for each Tablet is not more than 30 minutes.
Mix the batch, compress and de-dust the tablets and also perform the primary packing of Tablets at temperature not more than 25˚ C.
Yield:
Theoretical Yield 100000 Tablets & Expected Practical Yield is 100000 +_5 %
Packing Details: Put 1000 tablets in each polybag.
Seal each polybag along with label.
Pack such 01 polybag in specified Plastic box.
Pack such 100 plastic boxes in Corrugated box to give a pack size of 100×1000’s tabs.
Seal each corrugated box with adhesive tape & label it properly by affixing the specified label.
MANUFACTURING PROCESS:
Preparation of Starch Paste: Prepare the starch paste in the manner given below using Steam Jacketed Starch Paste Preparation Tank by operating it as per its SOP. Dissolve 0.50 kgs of Sodium Benzoate in 1Ltr of purified water and stir continuously.
Add 5.0 kgs of Starch in 4 Liters of purified water and stir continuously to make smooth slurry.
Take 40 Liters of boiling water add the solution of Sodium Benzoate and starch slurry with constant stirring to get a uniform paste.
Sifting: Fit Stainless Steel Sieve #40 on the Sifter-I as per its SOP . Sift all the ingredients through it and collect separately in Stainless Steel Containers.
Blending: Blend the following ingredients using Roto Cube Blender by operating it as per its SOP for 60 minutes and collect in Stainless Steel Container.
Metformin HCL
Lactose.
Di Calcium Phosphate
Starch
Wet Granulation: Mix the above blended ingredients with the Starch paste using Rapid Mixer Granulator by operating it as per its SOP. Add starch paste in such a manner by following the procedure given below so as to achieve proper wetting.
Mix the blended powder and starch paste together in Rapid Mixer Granulator.
Wet Screening: Pass the wet dough through a Multi Mill by operating it as per its SOP to convert the moist mass into coarse, granular aggregates.
Drying: Dry the granules in Fluidized Bed Drier by operating it as per its SOP at temperature 600 – 700 C for 30 minutes. Cool the granules to room temperature. Repeat the same process for next lots.
Sifting: Fit Stainless Steel Sieve # 20 on the Sifter as per its SOP. Sift all the ingredients through it and collect in Stainless Steel Container. Break the oversized granules left over the mesh in Oscillating Granulator by operating it as per its SOP and resift them.
Check the total weight of dried granules. Determine the loss on drying and percentage yield of dried granules.
Lubrication: Add the following lubricating agents to the Roto Cube Blender and operate it as per SOP for 30 minutes. Collect the blended powder in Stainless Steel Containers.
Talcum
Magnesium Stearate
Aerosil
Send the granules for bulk testing to Quality Control Department for assay of Active Ingredients.
Compression: Shift all the granules for compression to Tablet Compression Machine 27 Stations by operating it as per its SOP and collect the compressed tablets in Stainless Steel Container. Inspection: Transfer all the tablets to tablet inspection machine and sort out the defected tablet by operating it as per its SOP and collect the selected tablets in Stainless Steel Container.
Loose Packing: Shift the inspected tablets for Strip Packing.
IN-PROCESS CONTROLS: The following in-process controls should be maintained during the processing:
Check Raw materials used for manufacturing purpose are all approved materials and have ‘Released’ labels fixed on it.
All weighed Raw materials should be counter-checked by Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of Production Pharmacist and QC/QA Manager.
Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.
Humidity and temperature should be maintained during the compression of thermolabile products.
Sample of dried granules should be sent to Quality Control Department for the determination of Moisture content.
The total weight of blended powder should be checked in the presence of Manufacturing Chemist and record the same in Batch Manufacturing Record.
Bulk sample should be sent for analysis to Quality Control Department before starting compression of tablets.
Weight Variation: Intermittently weight variation of compressed tablets should be checked at 30 minutes interval by the Manufacturing Chemist and record for the same should be kept in Batch Manufacturing Record.
Out-of-limit tablets should be checked by Weight Variation Method as given below:
Take the average weight of 20 tablets on the calibrated balance and calculate the upper and lower limit as per the table given below in accordance with IP/BP:
| AVERAGE WEIGHT OF TABLETS (in mg) | MAXIMUM PERCENTAGE DIFFERENCE ALLOWED |
| 80mg or less | 10 |
| More than 80mg and less than 250mg | 7.5 |
| 250mg or more | 5 |
Take the weight of individual tablets and check if all the tablets are lying with in the limits.
Select the tablets only if no more than two tablets are out of 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 weight adjustment cam clockwise or anticlockwise accordingly as per the MFR of Compression Machine.
Re-check the weight of tablets for further adjustment, if any.
Thickness of Tablets: Thickness of the tablets should be determined by means of 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. Hardness of the compressed tablets should be checked at regular interval to determine the need for pressure adjustments on the tableting machine.
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 calibrated balance. Transfer the tablets in 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 the wear.
Take 10 tablets to check the friability, when the average weight of 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 interval of 1 hour by using 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 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 through out the test by suitably setting the thermostat.
Introduce a tube assembly unit into glass beaker in such a way that wire mesh at the base of each tube is at least 2.5cm below the surface of liquid when the basket is at 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 tube, stop the stopwatch. Note the time taken for disintegration of the tablets and record the same in 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, sorting of rejected tablets should be done as per SOP.
The strips and cartons should be checked thoroughly for proper batch coding.
Manufacturing Chemist and Production Pharmacist should randomly check that the correct no. of strips are being packed in each cartons and also the number of cartons in each shipper is exactly the same as that shown in proof.
Intimation should be sent to Quality Control Department for finished product sampling and testing.
After the completion of labelling and packaging, the coded cartons should be accounted for and rejected printed material should be destroyed in the presence of QC/QA Manager. Fill the destruction sheet and attach the same in the Batch Manufacturing Record.
It will be ensure that filling or packaging equipment has been properly cleaned after the completion of batch.
Filling or packaging of next product should not commence until the IPQA has given the ‘Line Clearance’.