High Quality USP/EP/BP GMP DMF FDA Proguanil Tablets CAS NO 500-92-5 Producer

Antiprotozoal (malaria).

Definition

Proguanil Tablets contain Proguanil Hydrochloride.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of proguanil hydrochloride, C11H16ClN5,HCl

A.  To a quantity of the powdered tablets containing 0.2  g of Proguanil Hydrochloride add 25  ml of methanol, shake for 10  minutes, filter, evaporate the filtrate to dryness and dry the residue at 105°. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of proguanil hydrochloride (RS 294).

B.  Boil a quantity of the powdered tablets containing 0.5  g of Proguanil Hydrochloride with 5  ml of 2m hydrochloric acid, cool and filter. To the filtrate add a slight excess of 5m sodium hydroxide, extract with 30  ml of ether, evaporate the ether and dry the residue at 105°. The melting point of the residue is about 131°, Appendix V A.

Tests

4-Chloroaniline

To a quantity of the powdered tablets containing 0.1  g of Proguanil Hydrochloride add 5  ml of ethanol (96%) and shake for 10  minutes. Add 2.5  ml of 2m hydrochloric acid and 15  ml of water, mix and filter through a moistened filter paper, washing the filter with 5  ml of water. Cool the filtrate to 5°, add 1  ml of 0.05m sodium nitrite, allow to stand at 5° for 5  minutes, add 2  ml of a 5% w/v solution of ammonium sulphamate and allow to stand for 10  minutes. Add 2  ml of a 0.1% w/v solution of N-(1-naphthyl)ethylenediamine dihydrochloride, dilute to 50  ml with water and allow to stand for 30  minutes. Any magenta colour produced is not more intense than that obtained by treating in the same manner and at the same time 20  ml of a solution containing 1.25 µg per ml of 4-chloroaniline (250  ppm).

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 50  ml of methanol to a quantity of the powdered tablets containing 0.1  g of Proguanil Hydrochloride, shake for 10  minutes, dilute to 100  ml with methanol, mix, filter and dilute 5  ml of the filtrate to 50  ml with the mobile phase. For solution (2) dilute 1  volume of solution (1) to 100  volumes with the mobile phase. For solution (3) mix 1  volume of a 0.05% w/v solution of 1-(2,5-dichlorophenyl)-5-isopropylbiguanide hydrochloride BPCRS in methanol with 9  volumes of a 0.010% w/v solution of proguanil hydrochloride BPCRS in the mobile phase.

The chromatographic procedure may be carried out using (a) a stainless steel column (10  cm × 5  mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable) and maintained at 40°, (b) as the mobile phase with a flow rate of 1  ml per minute a solution prepared by dissolving 1.89  g of sodium hexanesulphonate in a mixture of 500  ml of methanol, 500  ml of water and 5  ml of glacial acetic acid and (c) a detection wavelength of 254  nm.

The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated peaks due to proguanil hydrochloride and 1-(2,5-dichlorophenyl)-5-isopropylbiguanide hydrochloride.

The sum of the areas of any secondary peaks in the chromatogram obtained with solution (1) is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900  ml of 0.2m hydrochloric acid containing 0.2% w/v of sodium chloride and rotate the paddle at 50 revolutions per minute. Withdraw a sample of 10  ml of the medium, filter and dilute 2  ml of the filtrate to 10  ml with dissolution medium. Measure the absorbance of this solution, Appendix II B, at 242  nm using dissolution medium in the reference cell. Measure the absorbance of a 0.001% w/v solution of proguanil hydrochloride BPCRS in dissolution medium using dissolution medium in the reference cell. Calculate the total content of proguanil hydrochloride, C11H16ClN5,HCl, in the medium from the absorbances obtained and from the declared content of C11H16ClN5,HCl in proguanil hydrochloride BPCRS.

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) weigh and powder 20  tablets, add 50  ml of methanol to a quantity of the powdered tablets containing 0.1  g of Proguanil Hydrochloride, shake for 10  minutes, dilute to 100  ml with methanol, mix and filter. To 5  ml of the filtrate add sufficient methanol to produce 50  ml and dilute 10  ml of the resulting solution to 50  ml with the mobile phase. Solution (2) contains 0.002% w/v of proguanil hydrochloride BPCRS in the mobile phase. For solution (3) mix 1  volume of a 0.05% w/v solution of 1-(2,5-dichlorophenyl)-5-isopropylbiguanide hydrochloride BPCRS in methanol with 9  volumes of a 0.010% w/v solution of proguanil hydrochloride BPCRS in the mobile phase.

The chromatographic procedure described under Related substances may be used.

The assay is not valid unless the chromatogram obtained with solution (3) shows two clearly separated peaks due to proguanil hydrochloride and 1-(2,5-dichlorophenyl)-5-isopropylbiguanide hydrochloride.

Calculate the content of C11H16ClN5,HCl in the tablets using the declared content of C11H16ClN5,HCl in proguanil hydrochloride BPCRS.

The impurities limited by the requirements of this monograph include those listed in the monograph for Proguanil Hydrochloride.