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JOURNAL OF THE AMERICAN PHARMACEUTICAL ASSOCIATION .
PRACTICAL PHARMACY EDITION
hold it in the nonluminous portion of the flame of a Bunsen burner: the flame turns green (presence of chlorine). Prepare 25 ml. of 1 per cent chlorcyclizine hydrochloride. To 5 ml. of this solution add 2 ml. of nitric acid and 2 ml. of silver nitrate T .S. : a white precipitate forms (presen ce of
halides). To 20 ml. of the 1 per cent solution add 20 ml. of 1 % picric acid: a fine, yellow, crystalline precipitate forms . Filter the mixture and recrystallize the precipitate from alcohol and dry it at 105 0 C. for 4 hours: the picric obtained melts between 215 and 219 0 C. with decomposition. A 0 .001 % solution prepared as described later in the assay for chlorcyclizine hydrochloride exhibits an ultraviolet absorption maximum at 2300 A [specific absorbancy, E(l %, 1 em), 443 ± 10] and a minimum at 2180 A.
Purity Tests: Dry about 1 Gm. of chlorcyclizine hydrochloride, accurately weighed , for 3 hours at 120 0 C . : the loss in weight is not more than 2.0%. Ignite about 1 Gm. of chlorcyclizine hydrochloride , accurately weighed: the residue is not more than 0.20 % .
Council descriptwns of new drug products only are published regularly in THIS JOURNAL as they are accepted. Rules upon which the Council bases its action appeared in the July (7:320) 1946 issue, and may be secured in pamphlet form upon request to the Secretary, Council on Pharmacy and Chemistry, American Medical Association, 535 N. Dearborn St., Chicago 10. Ill.
CHLORCYCLIZINE HYDROCHLORIDE.Di-paralene Hydrochloride(Abbott.)- C 18 H 21 CIN2.HCl.- M. W. 337.29.- 1-(p-Chlorobenzhydryl) - 4 - methylpiperazine hydrochloride.The structural formula of chlorcyclizine hydrochloride may be represented as follows:
« )" /~ Cl-« )/ ""-/ CH- N
N - CH3 . HCI
Actions and Uses: (See general statement on Histamine-Antagonizing Agents.) Chlorcyclizine hydrochloride has prolonged action and low incidence of toxic effects. Symptomatic benefit from this antihistamine is somewhat more erratic than from others of the group. Dosage: Orally, SO mg. two or three times daily. Tests and Standards.Physical Properties: Chlorcyclizine hydrochloride is a white, odorless, crystalline solid with a bitter taste . It melts between 222.0 and 227.0 0 C. One part of chlorcyclizine hydrochloride is soluble in 1.6 parts of water , in 10.4 parts of alcohol, and in 3.6 parts of chloroform, and is practically insoluble in benzene and ether. The pH of a 1 % solution is between 5.0 and 5.5.
Identity Tests: Make 20 ml. of 1 % chlorcyclizine hydrochloride alkaline with sodium hydroxide T .S . and extract the liberated base with 25 ml. of ether. Evaporate the ether on a steam bath. I Dip a clean copper wire in the oily residue and
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Assay: (Chlorcyclizine Hydrochloride) Transfer 0.25 Gm. of chlorcyclizine hydrochloride, accurately weighed , to a 250-ml. volumetric flask and dilute to the mark with alcohol. Mix thoroughly and transfer 10 m!. of the solution to a 100mI. volumetric flask . Dilute to 100 m!. with alcohol, mix well and transfer 10 mI. of the solution to another 100-m!. volu metric flask and dilute to 100 m!. with alcohol. The final s olution (0.001 %) exhibits an ultraviolet absorption maxi mum at 2300 A [specific absorbancy, E (1 % , 1 em.), 443 ± 10]. Dosage Forms of Chlorcyclizine Hydrochloride
Tablets. Identity Tests: Agitate enough of the crushed tablets to yield about 0.5 Gm. of chlon;yclizine hydrochloride in 20 ml. of alcohol, centrifuge the mixture, pipette out 10 ml. of the clear supernatant liquid and add to it 20 ml. of 1% picric acid: a fine, yellow, crystalline precipitate forms. Proceed as directed in the third identity test in the monograph for Chlorcyclizine Hydrochloride starting with, "Filter the mixture, recrystallize the precipitate from alcohol. ... " Assay: (Chlorcyclizine Hydrochloride) Weigh 20 tablets and grind them. Accurately weigh the equivalent of SO mg. of chlorcyclizine hydrochloride and transfer it to a 50-ml. volumetric flask. Add about 25 ml. of alcohol. shake well to extract the chlorcyclizine hydrochloride and dilute to the mark with alcohol. J\1ix thoroughly, centrifuge and transfer S ml. of the clear supernatant liquid to another SOml. volumetric f1ask. Dilute to 50 ml. with alcohol, mix well and transfer 5 ml. of the solution to a third 50-ml. volumetric flask and dilute to 50 ml. with alcohol. Measure the optical density of the final solution (0.001 %) in a 1-cm. quartz cell with a spectrophotometer at 2300 A [specific absorbancy, EO %, 1 cm.), 443 ± 10]. The amount of chlorcyclizine hydrochloride present is not less than 9S.0 nor more than 105.0% of the labeled amount. Tablets Di-Paralene Hydrochloride: 2S mg. and 50 mg. Abbott Laboratories, North Chicago, Ill.
PRACTICAL PHARMACY EDITION
hold it in the nonluminous portion of the flame of a Bunsen burner: the flame turns green (presence of chlorine). Prepare 25 ml. of 1 per cent chlorcyclizine hydrochloride. To 5 ml. of this solution add 2 ml. of nitric acid and 2 ml. of silver nitrate T .S. : a white precipitate forms (presen ce of
halides). To 20 ml. of the 1 per cent solution add 20 ml. of 1 % picric acid: a fine, yellow, crystalline precipitate forms . Filter the mixture and recrystallize the precipitate from alcohol and dry it at 105 0 C. for 4 hours: the picric obtained melts between 215 and 219 0 C. with decomposition. A 0 .001 % solution prepared as described later in the assay for chlorcyclizine hydrochloride exhibits an ultraviolet absorption maximum at 2300 A [specific absorbancy, E(l %, 1 em), 443 ± 10] and a minimum at 2180 A.
Purity Tests: Dry about 1 Gm. of chlorcyclizine hydrochloride, accurately weighed , for 3 hours at 120 0 C . : the loss in weight is not more than 2.0%. Ignite about 1 Gm. of chlorcyclizine hydrochloride , accurately weighed: the residue is not more than 0.20 % .
Council descriptwns of new drug products only are published regularly in THIS JOURNAL as they are accepted. Rules upon which the Council bases its action appeared in the July (7:320) 1946 issue, and may be secured in pamphlet form upon request to the Secretary, Council on Pharmacy and Chemistry, American Medical Association, 535 N. Dearborn St., Chicago 10. Ill.
CHLORCYCLIZINE HYDROCHLORIDE.Di-paralene Hydrochloride(Abbott.)- C 18 H 21 CIN2.HCl.- M. W. 337.29.- 1-(p-Chlorobenzhydryl) - 4 - methylpiperazine hydrochloride.The structural formula of chlorcyclizine hydrochloride may be represented as follows:
« )" /~ Cl-« )/ ""-/ CH- N
N - CH3 . HCI
Actions and Uses: (See general statement on Histamine-Antagonizing Agents.) Chlorcyclizine hydrochloride has prolonged action and low incidence of toxic effects. Symptomatic benefit from this antihistamine is somewhat more erratic than from others of the group. Dosage: Orally, SO mg. two or three times daily. Tests and Standards.Physical Properties: Chlorcyclizine hydrochloride is a white, odorless, crystalline solid with a bitter taste . It melts between 222.0 and 227.0 0 C. One part of chlorcyclizine hydrochloride is soluble in 1.6 parts of water , in 10.4 parts of alcohol, and in 3.6 parts of chloroform, and is practically insoluble in benzene and ether. The pH of a 1 % solution is between 5.0 and 5.5.
Identity Tests: Make 20 ml. of 1 % chlorcyclizine hydrochloride alkaline with sodium hydroxide T .S . and extract the liberated base with 25 ml. of ether. Evaporate the ether on a steam bath. I Dip a clean copper wire in the oily residue and
192
Assay: (Chlorcyclizine Hydrochloride) Transfer 0.25 Gm. of chlorcyclizine hydrochloride, accurately weighed , to a 250-ml. volumetric flask and dilute to the mark with alcohol. Mix thoroughly and transfer 10 m!. of the solution to a 100mI. volumetric flask . Dilute to 100 m!. with alcohol, mix well and transfer 10 mI. of the solution to another 100-m!. volu metric flask and dilute to 100 m!. with alcohol. The final s olution (0.001 %) exhibits an ultraviolet absorption maxi mum at 2300 A [specific absorbancy, E (1 % , 1 em.), 443 ± 10]. Dosage Forms of Chlorcyclizine Hydrochloride
Tablets. Identity Tests: Agitate enough of the crushed tablets to yield about 0.5 Gm. of chlon;yclizine hydrochloride in 20 ml. of alcohol, centrifuge the mixture, pipette out 10 ml. of the clear supernatant liquid and add to it 20 ml. of 1% picric acid: a fine, yellow, crystalline precipitate forms. Proceed as directed in the third identity test in the monograph for Chlorcyclizine Hydrochloride starting with, "Filter the mixture, recrystallize the precipitate from alcohol. ... " Assay: (Chlorcyclizine Hydrochloride) Weigh 20 tablets and grind them. Accurately weigh the equivalent of SO mg. of chlorcyclizine hydrochloride and transfer it to a 50-ml. volumetric flask. Add about 25 ml. of alcohol. shake well to extract the chlorcyclizine hydrochloride and dilute to the mark with alcohol. J\1ix thoroughly, centrifuge and transfer S ml. of the clear supernatant liquid to another SOml. volumetric f1ask. Dilute to 50 ml. with alcohol, mix well and transfer 5 ml. of the solution to a third 50-ml. volumetric flask and dilute to 50 ml. with alcohol. Measure the optical density of the final solution (0.001 %) in a 1-cm. quartz cell with a spectrophotometer at 2300 A [specific absorbancy, EO %, 1 cm.), 443 ± 10]. The amount of chlorcyclizine hydrochloride present is not less than 9S.0 nor more than 105.0% of the labeled amount. Tablets Di-Paralene Hydrochloride: 2S mg. and 50 mg. Abbott Laboratories, North Chicago, Ill.