Neomallermin tr tablet 6mg

●Dissolution:
[pH1.2] Perform the test with 1 tablet of d-Chlorpheniramine Maleate Extenderelease
Tablets at 50 revolutions per minute according to the Paddle method using 900 mL of
1st fluid for dissolution test as the test solution. Withdraw 20 mL or more of the
dissolution medium after a predetermined period of time from the start of the
Dissolution Test, and filter through a membrane filter with a pore size of not exceeding
0.45 μm. Discard the first 10 mL of the filtrate, pipet exactly V mL of the subsequent
filtrate, and add 1st fluid for dissolution test to make exactly V’ mL so that each mL
contains about 6.7 μg of d-chlorpheniramine maleate (C16H19ClN2･C4H4O4) according to
the labeled amount. Pipet exactly 10 mL of this solution, add 2nd fluid for dissolution
test to make exactly 20 mL, and use this solution as the sample solution. Separately, dry
d-Chlorpheniramine Maleate Reference Standard at 65°C for 4 hours, weigh accurately
about 33 mg of it, and dissolve in 1st fluid for dissolution test to make exactly 100 mL.
Pipet exactly 2 mL of this solution, and add 1st fluid for dissolution test to make exactly
100 mL. Pipet exactly 10 mL of this solution, add 2nd fluid for dissolution test to make
exactly 20 mL, and use this solution as the standard solution. Perform the test with
exactly 50 μL each of the sample solution and the standard solution as directed under
Liquid Chromatography <2.01> according to the following conditions, and determine
the peak areas, AT and AS, of d-chlorpheniramine of these solutions.
d-Chlorpheniramine Maleate Extenderelease Tablets comply with the test if they
meet the dissolution requirements.

Dissolution rate (%) of d-chlorpheniramine maleate (C16H19ClN2･C4H4O4) to the labeled

amount
=W S ×( A T / A S ) ×( V '/ V ) ×( 1/C )×18
WS: Amount (mg) of d-Chlorpheniramine Maleate Reference Standard
C: Labeled amount (mg) of d-chlorpheniramine maleate (C16H19ClN2 ･ C4H4O4) in 1
tablet

[pH6.8] Perform the test with 1 tablet of d-Chlorpheniramine Maleate Extenderelease

Tablets at 50 revolutions per minute according to the Paddle method using 900 mL of
2nd fluid for dissolution test as the test solution. Withdraw exactly 20 mL of the
dissolution medium after a predetermined period of time from the start of the
Dissolution Test, and immediately fill up the dissolution medium each time with exactly
20 mL of fresh 2nd fluid for dissolution test, previously warmed to 37 ± 0.5°C. Filter
these dissolution mesium through a membrane filter with a pore size of not exceeding
0.45 μm. Discard the first 10 mL of the filtrate, pipet exactly V mL of the subsequent
filtrate, add 2nd fluid for dissolution test to make exactly V’ mL so that each mL
contains about 6.7 μg of d-chlorpheniramine maleate (C16H19ClN2･C4H4O4) according to
the labeled amount, and use this solution as the sample solution. Separately, dry d-
Chlorpheniramine Maleate Reference Standard at 65°C for 4 hours, weigh accurately
about 33 mg of it, and dissolve in 2nd fluid for dissolution test to make exactly 100 mL.
Pipet exactly 2 mL of this solution, add 2nd fluid for dissolution test to make exactly
100 mL, and use this solution as the standard solution. Perform the test with exactly 50
μL each of the sample solution and the standard solution as directed under Liquid
Chromatography <2.01> according to the following conditions, and determine the peak
areas, AT and AS, of d-chlorpheniramine of these solutions.
d-Chlorpheniramine Maleate Extenderelease Tablets comply with the test if they
meet the dissolution requirements.

Dissolution rate (%) in each case of n with respect to the labeled amount of d-
chlorpheniramine maleate (C16H19ClN2･C4H4O4) (n=1,2)

{ ( )}
A T ( n) n−1 A T (i ) 1 V' 1
=W S × +∑ × × × ×18
AS i=1 AS 45 V C

WS: Amount (mg) of d-Chlorpheniramine Maleate Reference Standard

C: Labeled amount (mg) of d-chlorpheniramine maleate (C16H19ClN2 ･ C4H4O4) in 1
tablet

Test conditions
Detector: An ultraviolet absorption photometer (wavelength: 262 nm)
Column: A stainless steel column 4.6 mm in inside diameter and 15 cm in length,
packed with octadecylsilanized silica gel for liquid chromatography (5 μm in particle
diameter).
Column temperature: A constant temperature of about 40°C.
Mobile phase: Dissolve 3.0 g of sodium lauryl sulfate and 1 mL of phosphoric acid in
water to make 1000 mL. To 900 mL of this solution add 1100 mL of acetonitrile.
Flow rate: Adjust the flow rate so that the retention time of d-chlorpheniramine is about
6 minutes.
System suitability
System performance: When the procedure is run with 50 μL of the standard solution
under the above operating conditions, the number of theoretical plates and the symmetry
factor of the peak of d-chlorpheniramine are not less than 3000 and not more than 2.0,
respectively.
System repeatability: When the test is repeated 6 times with 50 μL of the standard
solution under the above operating conditions, the relative standard deviation of the
peak area of d-chlorpheniramine is not more than 2.0%.

Dissolution requirements
Labeled amount Predetermined period Dissolution rate
120 min. (pH1.2) 40 to 60 %
6 mg 4 hours (pH6.8) 25 to 55 %
24 hours (pH6.8) Not less than 85%

●Uniformity of dosage units: Perform the test according to the following method: it
meets the requirement of the Content uniformity test.
To 1 tablet of Neomallermin tr tablet 6mg add 30 mL of a mixture of methanol and 0.1
mol/L hydrochloric acid TS (1: 2), treat with ultrasonic waves until the tablet is
disintegrated, shake, and add a mixture of methanol and 0.1 mol/L hydrochloric acid TS
(1: 2) to make exactly 50 mL. Centrifuge this solution, and filter the supernatant liquid
through a membrane filter with a pore size of 0.45 μm. Discard the first 5 mL of the
filtrate, and use the subsequent filtrate as the sample solution. Separately, dry d-
chlorpheniramine maleate for assay at 65°C for 4 hours, weigh accurately about 24 mg
of it, dissolve in a mixture of methanol and 0.1 mol/L hydrochloric acid TS (1: 2) to
make exactly 200 mL, and use this solution as the standard solution. Perform the test
with exactly 10 μL each of the sample solution and the standard solution as directed
under Liquid Chromatography according to the following conditions, and determine the
peak areas, AT and AS, of d-chlorpheniramine of these solutions.

Amount (mg) of d-chlorpheniramine maleate (C16H19ClN2･C4H4O4)

= amount (mg) of d-chlorpheniramine maleate for assay ×AT／AS×1／4
(1／4: Dilution coefficient)

Test condition
Detector: An ultraviolet absorption photometer (wavelength: 262 nm)
Column: A stainless steel column 4.6 mm in inside diameter and 15 cm in length,
packed with octadecylsilanized silica gel for liquid chromatography (5 μm in particle
diameter).
Column temperature: A constant temperature of about 40°C.
Mobile phase: Dissolve 3.0 g of sodium lauryl sulfate and 1 mL of phosphoric acid in
water to make 1000 mL. To 900 mL of this solution add 1100 mL of acetonitrile.
Flow rate: Adjust the flow rate so that the retention time of d-chlorpheniramine is about
6 minutes.
System suitability
System performance: When the procedure is run with 10 μL of the standard solution
under the above operating conditions, the number of theoretical plates and the symmetry
factor of the peak of d-chlorpheniramine are not less than 3000 and not more than 2.0,
respectively.
System repeatability: When the test is repeated 6 times with 10 μL of the standard
solution under the above operating conditions, the relative standard deviation of the
peak area of d-chlorpheniramine is not more than 2.0%.

●Assay: Weigh accurately and powder not less than 20 Neomallermin tr tablet 6mg.
Weigh accurately about 0.195 g (equivalent to about 6 mg of d-chlorpheniramine
maleate (C16H19ClN2 ･C4H4O4)) of it, shake with 30 mL of 0.1 mol/L hydrochloric acid
TS, and add 0.1 mol/L hydrochloric acid TS to make exactly 50 mL. Centrifuge this
solution, and filter the supernatant liquid through a membrane filter with a pore size of
not exceeding 0.45 μm. Discard the first 5 mL of the filtrate, and use the subsequent
filtrate as the sample solution. Separately, dry d-chlorpheniramine maleate for assay at
65°C for 4 hours, weigh accurately about 24 mg of it, dissolve in 0.1 mol/L hydrochloric
acid TS to make exactly 200 mL, and use this solution as the standard solution. Perform
the test with exactly 10 μL each of the sample solution and the standard solution as
directed under Liquid Chromatography according to the following conditions, and
determine the peak areas, AT and AS, of d-chlorpheniramine of these solutions.

Amount (mg) of d-chlorpheniramine maleate (C16H19ClN2･C4H4O4)

= amount (mg) of d-chlorpheniramine maleate for assay ×AT／AS×1／4
(1／4: Dilution coefficient)
Test condition
Detector: An ultraviolet absorption photometer (wavelength: 262 nm)
Column: A stainless steel column 4.6 mm in inside diameter and 15 cm in length,
packed with octadecylsilanized silica gel for liquid chromatography (5 μm in particle
diameter).
Column temperature: A constant temperature of about 40°C.
Mobile phase: Dissolve 3.0 g of sodium lauryl sulfate and 1 mL of phosphoric acid in
water to make 1000 mL. To 900 mL of this solution add 1100 mL of acetonitrile.
Flow rate: Adjust the flow rate so that the retention time of d-chlorpheniramine is about
6 minutes.
System suitability
System performance: When the procedure is run with 10 μL of the standard solution
under the above operating conditions, the number of theoretical plates and the symmetry
factor of the peak of d-chlorpheniramine are not less than 3000 and not more than 2.0,
respectively.
System repeatability: When the test is repeated 6 times with 10 μL of the standard
solution under the above operating conditions, the relative standard deviation of the
peak area of d-chlorpheniramine is not more than 2.0%.

Specification
Neomallermin tr tablet 6mg contain not less than 95.0％ and not more than 105.0％ of
the labeled amount of d-chlorpheniramine maleate (C16H19ClN2･C4H4O4：390.86).
●4 Media dissolution test: Dissolution profile
Test conditions
Rotation frequency
Test solutions Sampling time (min.)
(rpm)
pH 1.2 (1st fluid for dissolution
15,30,60,90,120
test)
0.05 mol/L acetic acid-sodium
15,30,60,90,120,180,240,
acetate buffer solution with pH
300,360,480,600,720,1440
4.0 50
pH 6.8 (2nd fluid for 15,30,60,90,120,180,240,
dissolution test) 300,360,480,600,720,1440
15,30,60,90,120,180,240,
Water（purified water）
300,360,480,600,720,1440
Amount of test solution：900mL
Temperature of test solution：37.0±0.5℃

［For pH1.2］
＜Sample solution＞（6 vessels）
Drug product（Neomallermin TR Tablet 6mg）
1 tablet (equivalent to 6 mg of d-Chlorpheniramine maleated)
　
Dissolution test

10 mL of sampling solution at each sampling time (immediately replaced with another 10 mL)
Membrane filtration (with a pore size of not exceeding 0.45 μm) (Filter:Millex-LH, produced by
Merck)
(discarding the first 5 mL of the filtrate)

Filtrate,1 volume (exactly)

←0.5mol/L Phosphate buffer solution, pH 6.8,1 volume (exactly)
Mixing・・・sample solution

＜Standard solution＞Repeat count: 1

d-Chlorpheniramine maleate RS about 33mg （ accurately ） （ after being dried at 65°C for 4
hours）
 ←Test solution
100mL（exactly）
2mL（exactly）
←Test solution
100mL（exactly）
1 volume（exactly）
←0.5mol/L Phosphate buffer solution, pH 6.8,1 volume (exactly)
Mixing・・・standard solution

【For pH4.0，pH6.8 and water】

＜Sample solution＞（6 vessels）
Drug product（Neomallermin TR Tablet 6mg）
1 tablet (equivalent to 6 mg of d-Chlorpheniramine maleated)
　
Dissolution test

10 mL of sampling solution at each sampling time (immediately replaced with another 10 mL)
Membrane filtration (with a pore size of 0.45 μm) (Filter:Millex-LH, produced by Merck)
(discarding the first 5 mL of the filtrate)

Filtrate・・・sample solution

＜Standard solution＞repetition: 1
d-Chlorpheniramine maleate RS about 33mg （ accurately ） （ after being dried at 65°C for 4
hours）
←Test solution
100mL（exactly）
2mL（exactly）
←Test solution
100mL（exactly）・・・standard solution

＜Test conditions＞
Detector: An ultraviolet absorption photometer（wavelength：262nm）
Column： Mightysil RP-18 GP 5 μm（4.6×150mm），produced by Kanto Chemical
Column temperature：A constant temperature of about 40℃
Injection volume：50μL
Mobile phase：Dissolve 3.0g of sodium lauryl sulfate and 1mL of phosphoric acid in water to make
1000mL.To 900 mL of this solution add 1100 mL of acetonitrile
Flow rate：Adjust the flow rate so that the retention time of d-chlorpheniramine is about 6 minutes.

＜System suitability＞
System performance: When the procedure is run with 50 μL of the standard solution under the above
operating conditions, the number of theoretical plates and the symmetry factor of the peak of d-
chlorpheniramine are not less than 2000 and not more than 2.0, respectively.
System repeatability: When the test is repeated 6 times with 50 μL of the standard solution under the
above operating conditions, the relative standard deviation of the peak area of d-chlorpheniramine is
not more than 2.0%.

＜Reagents, Test solutions＞

0.5mol/L Phosphate buffer solution, pH 6.8
Dissolve 17.9 g of disodium hydrogen phosphate dodecahydrate in water to make 100 mL (solution
A). Dissolve 7.8 g of sodium dihydrogen phosphate dihydrate in water to make 100 mL (solution B).
To a volume of solution A add solution B until the mixture is adjusted to pH 6.8.