846 Ebastine Orally Disintegrating Tablets / Official Monographs JP XVII

similar intensities of absorption at the same wavelengths. ously dried, dissolve in 60 mL of acetic acid (100), and titrate
(3) Determine the infrared absorption spectrum of <2.50> with 0.1 mol/L perchloric acid VS (potentiometric
Ebastine as directed in the potassium bromide disk method titration). Perform a blank determination in the same man-
under Infrared Spectrophotometry <2.25>, and compare the ner, and make any necessary correction.
spectrum with the Reference Spectrum: both spectra exhibit
Each mL of 0.1 mol/L perchloric acid VS
similar intensities of absorption at the same wave numbers.
＝ 46.97 mg of C32H39NO2
Melting point <2.60> 84 – 879
C
Containers and storage Containers—Well-closed contain-
Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of ers.
Ebastine according to Method 2, and perform the test. Storage—Light-resistant.
Prepare the control solution with 2.0 mL of Standard Lead
Solution (not more than 20 ppm). A platinum crucible may
be used. Ebastine Orally Disintegrating
(2) Related substances—Dissolve 0.10 g of Ebastine in 50
mL of the mobile phase, and use this solution as the sample Tablets
solution. Pipet 5 mL of the sample solution, and add the
エバスチン口腔内崩壊錠
mobile phase to make exactly 100 mL. Pipet 2 mL of this so-
lution, add the mobile phase to make exactly 100 mL, and
use this solution as the standard solution. Perform the test Ebastine Orally Disintegrating Tablets contain not
with exacty 10 mL each of the sample solution and standard less than 95.0z and not more than 105.0z of the
solution as directed under Liquid Chromatography <2.01> labeled amount of ebastine (C32H39NO2: 469.66).
according to the following conditions, and determine each
Method of preparation Prepare as directed under Tablets,
peak area by the automatic integration method: each peak
with Ebastine.
area other than ebastine obtained from the sample solution
is not larger than the peak area of ebastine obtained from Identification Powder Ebastine Orally Disintegrating
the standard solution, and the total area of the peaks other Tablets. To a potion of the powder, equivalent to 30 mg of
than ebastine from the sample solution is not larger than 4 Ebastine, add 70 mL of methanol, shake for 10 minutes,
times the peak area of ebastine from the standard solution. then add methanol to make 100 mL, and centrifuge. To 5
Operating conditions— mL of the supernatant liquid add methanol to make 100 mL.
Detector: An ultraviolet absorption photometer (wave- Determine the absorption spectrum of this solution as di-
length: 220 nm). rected under Ultraviolet-visible Spectrophotometry <2.24>: it
Column: A stainless steel column 4.6 mm in inside diame- exhibits a maximum between 251 nm and 255 nm.
ter and 15 cm in length, packed with octadecylsilanized silica
Purity Related substances—Powder Ebastine Orally Disin-
gel for liquid chromatography (5 mm in particle diameter).
tegrating Tablets. To a portion of the powder, equivalent to
Column temperature: A constant temperature of about
50 mg of Ebastine, add 30 mL of methanol for liquid chro-
409 C.
matography, shake for 10 minutes, and add the mobile
Mobile phase: Dissolve 7.8 g of sodium dihydrogen phos-
phase to make 50 mL. Centrifuge this solution, and use the
phate dihydrate in 900 mL of water, adjust to pH 3.0 with
supernatant liquid as the sample solution. Pipet 1 mL of the
diluted phosphoric acid (1 in 5), and add water to make 1000
sample solution, add the mobile phase to make exactly 200
mL. To 375 mL of this solution add 625 mL of acetonitrile
mL, and use this solution as the standard solution. Perform
for liquid chromatography, and dissolve 0.72 g of sodium
the test with exactly 10 mL each of the sample solution and
lauryl sulfate in this solution.
standard solution as directed under Liquid Chromatography
Flow rate: Adjust so that the retention time of ebastine is
<2.01> according to the following conditions, and determine
about 9 minutes.
each peak area by the automatic integration method: the
Time span of measurement: About 2 times as long as the
area of the peak other than ebastine obtained from the sam-
retention time of ebastine, beginning after the solvent peak.
ple solution is not larger than the peak area of ebastine ob-
System suitability—
tained from the standard solution, and the total area of the
Test for required detectability: Pipet 5 mL of the standard
peaks other than ebastine from the sample solution is not
solution, and add the mobile phase to make exactly 10 mL.
larger than 2 times the peak area of ebastine from the stand-
Confirm that the peak area of ebastine obtained with 10 mL
ard solution.
of this solution is equivalent to 35 to 65z of that obtained
Operating conditions—
with 10 mL of the standard solution.
Column, column temperature, mobile phase, and flow
System performance: When the procedure is run with 10
rate: Proceed as directed in the operating conditions in the
mL of the standard solution under the above operating con-
Assay.
ditions, the number of theoretical plates and the symmetry
Detector: An ultraviolet absorption photometer (wave-
factor of the peak of ebastine are not less than 6000 and not
length: 220 nm).
more than 1.5, respectively.
Time span of measurement: About 3 times as long as the
System repeatability: When the test is repeated 6 times
retention time of ebastine, beginning after the solvent peak.
with 10 mL of the standard solution under the above operat-
System suitability—
ing conditions, the relative standard deviation of the peak
Test for required detectability: Pipet 10 mL of the stand-
area of ebastine is not more than 2.0z.
ard solution, and add the mobile phase to make exactly 50
Loss on drying <2.41> Not more than 0.5z (1 g, in vacu- mL. Confirm that the peak area of ebastine obtained with 10
um, phosphorus (V) oxide, 609C, 2 hours). mL of this solution is equivalent to 15 to 25z of that ob-
tained with 10 mL of the standard solution.
Residue on ignition <2.44> Not more than 0.1z (1 g).
System performance: When the procedure is run with 10
Assay Weigh accurately about 0.5 g of Ebastine, previ- mL of the standard solution under the above operating con-
JP XVII Official Monographs / Ebastine Tablets 847

ditions, the number of theoretical plates and the symmetry fuge. Pipet 5 mL of the supernatant liquid, add exactly 5 mL
factor of the peak of ebastine are not less than 6000 and not of the internal standard solution, and use this solution as the
more than 1.5, respectively. sample solution. Separately, weigh accurately about 50 mg
System repeatability: When the test is repeated 6 times of ebastine for assay, previously dried at 609C under
with 10 mL of the standard solution under the above operat- reduced pressure with phosphorous (V) oxide for 2 hours,
ing conditions, the relative standard deviation of the peak and dissolve in methanol to make exactly 50 mL. Pipet 5 mL
area of ebastine is not more than 2.0z. of this solution, add 5 mL of 0.1 mol/L hydrochloric acid
TS, and add methanol to make exactly 50 mL. Pipet 5 mL of
Uniformity of dosage units <6.02> Perform the test accord-
this solution, add exactly 5 mL of the internal standard solu-
ing to the following method: it meets the requirement of the
tion, and use this solution as the standard solution. Perform
Content uniformity test.
the test with 10 mL each of the sample solution and standard
To 1 tablet of Ebastine Orally Disintegrating Tablets add
solution as directed under Liquid Chromatography <2.01>
V/10 mL of 0.1 mol/L hydrochloric acid TS, and disperse
according to the following conditions, and calculate the
the particles with the aid of ultrasonic waves with occasional
ratios, QT and QS, of the peak area of ebastine to that of the
shaking. Add 3V/5 mL of methanol, shake for 10 minutes,
internal standard.
then add methanol to make exactly V mL so that each mL
contains about 0.1 mg of ebastine (C32H39NO2), and centri- Amount (mg) of ebastine (C32H39NO2)
fuge. Pipet 5 mL of the supernatant liquid, add exactly 5 mL ＝ MS × QT/QS × 2/5
of the internal standard solution, and use this solution as the
MS: Amount (mg) of ebastine for assay taken
sample solution. Then, proceed as directed in the Assay.
Internal standard solution—A solution of diphenyl in the
Amount (mg) of ebastine (C32H39NO2)
mobile phase (1 in 40,000).
＝ MS × QT/QS × V/500
Operating conditions—
MS: Amount (mg) of ebastine for assay taken Detector: An ultraviolet absorption photometer (wave-
length: 254 nm).
Internal standard solution—A solution of diphenyl in the
Column: A stainless steel column 4.6 mm in inside diame-
mobile phase (1 in 40,000).
ter and 15 cm in length, packed with octadecylsilanized silica
Disintegration Being specified separately when the drug is gel for liquid chromatography (5 mm in particle diameter).
granted approval based on the Law. Column temperature: A constant temperature of about
409C.
Dissolution <6.10> When the test is performed at 50 revolu-
Mobile phase: Dissolve 7.8 g of sodium dihydrogen phos-
tions per minute according to the Paddle method, using 900
phate dihydrate in 900 mL of water, adjust to pH 3.0 with
mL of 1st fluid for dissolution test as the dissolution me-
diluted phosphoric acid (1 in 5), and add water to make 1000
dium, the dissolution rate in 15 minutes of Ebastine Orally
mL. To 375 mL of this solution add 625 mL of acetonitrile
Disintegrating Tablets is not less than 80z.
for liquid chromatography, and dissolve 0.72 g of sodium
Start the test with 1 tablet of Ebastine Orally Disintegrat-
lauryl sulfate in this solution.
ing Tablets, withdraw not less than 20 mL of the medium at
Flow rate: Adjust so that the retention time of ebastine is
the specified minute after starting the test, and filter through
about 9 minutes.
a membrane filter with a pore size not exceeding 0.45 mm.
System suitability—
Discard the first 10 mL of the filtrate, pipet V mL of the
System performance: When the procedure is run with 10
subsequent filtrate, add the dissolution medium to make
mL of the standard solution under the above operating con-
exactly V? mL so that each mL contains about 5.6 mg of
ditions, the internal standard and ebastine are eluted in this
ebastine (C32H39NO2), and use this solution as the sample so-
order with the resolution between these peaks being not less
lution. Separately, weigh accurately about 28 mg of ebastine
than 5.
for assay, previously dried at 609 C under reduced pressure
System repeatability: When the test is repeated 6 times
with phosphorous (V) oxide for 2 hours, and dissolve in
with 10 mL of the standard solution under the above operat-
methanol to make exactly 50 mL. Pipet 1 mL of this solu-
ing conditions, the relative standard deviation of the ratio of
tion, add the dissolution medium to make exactly 100 mL,
the peak area of ebastine to that of the internal standard is
and use this solution as the standard solution. Determine the
not more than 1.0z.
absorbances, AT and AS, of the sample solution and stand-
ard solution at 258 nm as directed under Ultraviolet-visible Containers and storage Containers—Tight containers.
Spectrophotometry <2.24>, using the dissolution medium as Storage—Light-resistant.
the blank.
Dissolution rate (z) with respect to the labeled amount
of ebastine (C32H39NO2) Ebastine Tablets
＝ MS × AT/AS × V?/V × 1/C × 18
エバスチン錠
MS: Amount (mg) of ebastine for assay taken
C: Labeled amount (mg) of ebastine (C32H39NO2) in 1
Ebastine Tablets contain not less than 95.0z and
tablet
not more than 105.0z of the labeled amount of
Assay Weigh accurately the mass of not less than 20 ebastine (C32H39NO2: 469.66).
Ebastine Orally Disintegrating Tablets, and powder. Weigh
Method of preparation Prepare as directed under Tablets,
accurately a portion of the powder, equivalent to about 20
with Ebastine.
mg of ebastine (C32H39NO2), add 20 mL of 0.1 mol/L hydro-
chloric acid TS, and disperse the particles with the aid of Identification Powder Ebastine Tablets. To a potion of the
ultrasonic waves. Add 120 mL of methanol, shake for 10 powder, equivalent to 30 mg of Ebastine, add 70 mL of
minutes, add methanol to make exactly 200 mL, and centri- methanol, shake for 10 minutes, then add methanol to make