QualityGuidances

GENERAL MATERIAL INFORMATION
General Information	Cinnarizine and Dimenhydrinate film coated  tablets is consisting of Cinnarizine and Dimenhydrinate and Excipients.
Categories	Antihistamine
Composition	Each film coated tablet contains: Cinnarizine  IP …………20 mg Dimenhydrinate………   40 mg
Reference	As per In-House Specification
Sample Quantity	Chemical Analysis = 100 Tablets
Shelf Life	24 Months
Hazards and Precaution, If any	Use nose mask and hand gloves while sampling at bulk stage
Storage	Store protected from light.

 

SPECIFICATION OF FINISH PRODUCT

 

S.NO.	TESTS	SPECIFICATIONS			REFERENCE
1.	Description	Orange  colored, round shaped, biconvex, film coated tablet having both sides plain			IH
2.	Average weight	220mg ± 3%			IH
3.	Uniformity of weight	Within ± 7.5% of the Average weight			IP
4.	Identification For Cinnarizine and Dimenhydrinate	In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to peak in chromatogram obtained with the reference solution.			IH
5.	Hardness	NLT 4.0 kg/cm2			IH
6.	Disintegration Time	NMT 30 Minutes			IP
7.	Leak Test	Should be Pass			IP
8.	Assay:				IP
	Each film coated tablet contains:	Limit
		Claim	In mg	Claim
	Cinnarizine I.P.	20 mg	18 mg to 22 mg	90.0% to 110.0%
	Dimenhydrinate	40 mg	36 mg to 44 mg	90.0% to 110.0%
9.	Microbial Limit Test :				IH
	a)Total Bacterial count			NMT 1000 cfu/gm
	b)Total Fungal Count			NMT 100cfu/gm
	c)Specific pathogens	Escherichia Coli		Should be absent
		Salmonella abony		Should be absent
		Staphylococcus aureus		Should be absent
		Pseudomonas aeruginosa		Should be absent
		Clostridium sporogenes		Should be absent
		Shigella boydii		Should be absent
		Candida albicans		Should be absent

 

SPECIFICATION OF STABILITY ANALYSIS

 

S.NO.	TESTS	SPECIFICATIONS			REFERENCE
1.	Description	Orange  colored, round shaped, biconvex, film coated tablet having both sides plain			IH
2.	Average weight	220mg ± 3%			IH
3.	Uniformity of weight	Within ± 7.5% of the Average weight			IP
4.	Identification For Cinnarizine and Dimenhydrinate	In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to peak in chromatogram obtained with the reference solution.			IH
5.	Hardness	NLT 4.0 kg/cm2			IH
6.	Disintegration Time	NMT 30 Minutes			IP
7.	Assay:				IP
	Each film coated tablet contains:	Limit
		Claim	In mg	Claim
	Cinnarizine I.P.	20 mg	18 mg to 22 mg	90.0% to 110.0%
	Dimenhydrinate	40 mg	36 mg to 44 mg	90.0% to 110.0%
8.	Microbial Limit Test :   #				IH
	a)Total Bacterial count			NMT 1000 cfu/gm
	b)Total Fungal Count			NMT 100cfu/gm
	c)Specific pathogens	Escherichia Coli		Should be absent
		Salmonella abony		Should be absent
		Staphylococcus aureus		Should be absent
		Pseudomonas aeruginosa		Should be absent
		Clostridium sporogenes		Should be absent
		Shigella boydii		Should be absent
		Candida albicans		Should be absent

# Microbial test -Once in a year

 

STANDARD TESTING PROCEDURE

 

• Description: Visual
• Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula.

Average weight (mg) =   wt of 20 tablets (gm) x 1000

20

3.0)                  Uniformity of weight:

Weigh 20 tablets selected at random and calculate the average weight. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in table.

Tablets were weighed individually and the percentage of deviation of its weight from the average weight was determined for each tablet. Formula to calculate the percentage of deviation.

Deviation (%) = Weight of each tablet – Average weight    x 100

Average weight

Average weight of tablets	Percentage deviation
More than 80mg but Less than 250mg	±7.5%

• Identification:

In the assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.

5.0)      Hardness:

The standard method used for tablet hardness testing is compression testing. The tablet is placed between two jaws that crush the tablet. The machine measures the force applied to the tablet and detects when it fractures.

6.0)      Disintegration Time:

Unless otherwise stated in the individual monograph, introduce one tablet into each tube and add a disc to each tube. The assembly is suspended in the liquid medium in a suitable vessel, preferably a 1-litre beaker. The volume of liquid is such that the wire mesh at its highest point is at least 15 mm below the surface of the liquid, and at its lower point is at least 25 mm above the bottom of the beaker. At no time should the top of the basket-rack assembly become submerged. There is a thermostatic arrangement for heating the liquid and maintaining the temperature at 37±2°.

If 1 or 2 tablets fail to disintegrate, repeat the test on 12 additional tablets; not less than 16 of the total of 18 tablets tested disintegrate.

If the tablets adhere to the disc and the preparation under examination fails to comply, repeat the test omitting the disc. The preparation complies with the test if all the tablets in the repeat test disintegrate.

7.0)      Leak test:

The apparatus is used to test for the integrity of packed strips, blisters and Alu-Alu Blister pack containing tablets. Ensure apparatus bath is filled with purified water up to mark indicated and add 0.5% crystal violet solution in water. Samples are placed into the desiccators and the lid is placed in position. The pump starts to produce a vacuum 15inHg inside the desiccators and the vacuum is held for 1 minute. The sample remains at the required vacuum level for given time interval buzzer will sound after time is over and will cut off the vacuum pump. As the package is immersed in a colored dye solution the venting of the desiccators will allow any holes to be penetrated by the dye and the contents of the flexible packaging will also be stained with the same coloring material.

Examine all the strips for any leakage by opening the pockets manually. If anyone pocket shows evidence of leakage, reject the sample, stop the Blister / Strip machine and immediately take corrective action.

8.0)      Assay: Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Weigh accurately a quantity of the powder containing about 20 mg Cinnarizine, and 40mg Dimenhydrinate disperse in 50 ml mobile phase with the aid of ultrasound for 15 minutes and dilute to 100 ml with mobile phase and filter.

Reference solution: Weigh reference standard of Cinnarizine 20 mg and reference standard of Dimenhydrinate 40 mg in 100 ml volumetric flask. Disperse in 50 ml mobile phase with the aid of ultrasound for 15 minutes and dilute to 100 ml with mobile phase and filter.

             Chromatographic system:

• A stainless steel column C18, 4.6mm X 100 cm,
• Mobile phase: 340 ml methanol + 40 ml acetonitrile+20 ml water add 1 drop of triethylamine.
• Flow rate: 1.5 ml per minute,
• Spectrophotometer set at 254 nm,
• Injection volume: 20 µl
• Column temperature: 30°

Inject the reference solution and the test solution.

Calculate the content of Cinnarizine and Dimenhydrinate in the tablets.

Formula:

Area of Test      STD Wt.(mg)          100               Potency

—————–X——————X——————X———–X Average wt.

Area of STD            100              Test Wt.(mg)        100

          Acceptance criteria: 90.0%-110.0%

9.0)   Abbreviations:

           Wt.                    : Weight

rpm                   : Rotations per minute

ml                      : Milliliter

w/v                    : Weight/Volume

inHg                  : Inch of Mercury

STD                 : Standard

mg                    : Milligram

 

10.0) Revision History:-

S. No.	Reason For Change	Revision No.