Fluphenazine Tablets

General Notices

Action and use

Dopamine receptor antagonist; neuroleptic.

Definition

Fluphenazine Tablets contain Fluphenazine Hydrochloride. They are coated.

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

Content of fluphenazine hydrochloride, C22H26F3N3OS,2HCl

90.0 to 110.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the powdered tablets with sufficient methanol to produce a solution containing 0.2% w/v of Fluphenazine Hydrochloride, centrifuge and use the supernatant liquid.
(2) 0.2% w/v of fluphenazine hydrochloride BPCRS in methanol.
chromatographic conditions
(a) Use as the coating kieselguhr G. Impregnate the dry plate by placing it in a tank containing a shallow layer of a mixture of 5 volumes of 2-phenoxyethanol, 15 volumes of formamide and 180 volumes of acetone, allowing the impregnating solvent to ascend to the top, removing the plate from the tank and using it immediately.
(b) Use the mobile phase as described below.
(c) Apply 2 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, examine under ultraviolet light (365 nm) and observe the fluorescence produced after about 2 minutes. Heat the plate at 120° for 20 minutes, cool, spray with ethanolic sulfuric acid (20%) and observe the colour produced.
mobile phase

2 volumes of diethylamine and 100 volumes of petroleum spirit (boiling range, 40° to 60°) saturated with 2-phenoxyethanol.

confirmation

The principal spot in the chromatogram obtained with solution (1) corresponds in position, fluorescence and colour to that in the chromatogram obtained with solution (2).

B. Extract a quantity of the powdered tablets containing 5 mg of Fluphenazine Hydrochloride with 5 mL of acetone, filter and evaporate the filtrate to dryness. Add 2 mL of sulfuric acid to the residue and allow to stand for 5 minutes. An orange colour is produced.
C. Extract a quantity of the powdered tablets containing 10 mg of Fluphenazine Hydrochloride with 10 mL of absolute ethanol containing 0.2% v/v of 13.5m ammonia and evaporate the extract to dryness. Heat 0.5 mL of chromic–sulfuric acid mixture in a small test tube in a water bath for 5 minutes; the solution wets the side of the tube readily and there is no greasiness. Add 2 or 3 mg of the residue and again heat in a water bath for 5 minutes; the solution does not wet the side of the tube and does not pour easily from the tube.

Tests

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Remove the coating from a suitable number of tablets; shake a quantity of the powdered tablet cores containing 20 mg of Fluphenazine Hydrochloride with 10 mL of 0.1m methanolic sodium hydroxide for 5 minutes, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 50 volumes with 0.1m methanolic sodium hydroxide.
(3) Dilute 1 volume of solution (1) to 100 volumes with 0.1m methanolic sodium hydroxide.
chromatographic conditions
(a) Use as the coating silica gel GF254.
(b) Use the mobile phase as described below.
(c) Apply 50 µL of solution (1). Apply 25 µL of solutions (2) and (3).
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).
mobile phase

5 volumes of 13.5m ammonia, 30 volumes of cyclohexane and 80 volumes of acetone.

limits

Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (1%) and not more than two such spots are more intense than the spot in the chromatogram obtained with solution (3) (0.5%). Disregard any spot remaining on the line of application.

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Fluphenazine Hydrochloride comply with the requirements stated under Tablets using the following method of analysis. Carry out the following procedure protected from light. Record second-derivative ultraviolet absorption spectra of the following solutions in the range 230 to 300 nm, Appendix II B. For solution (1) add 2 mL of 0.1m hydrochloric acid to one tablet and mix with the aid of ultrasound until the tablet is dispersed. Add 60 mL of a mixture of 1 volume of 1m hydrochloric acid and 99 volumes of ethanol (80%), shake for 20 minutes, dilute to 100 mL with the same solvent mixture, mix and filter. Solution (2) contains 0.001% w/v of fluphenazine hydrochloride BPCRS.

For each solution measure the amplitude from the peak at about 266 nm to the trough at about 258 nm. Calculate the content of C22H26F3N3OS,2HCl in each tablet using the declared content of C22H26F3N3OS,2HCl in fluphenazine hydrochloride BPCRS.

Assay

For tablets containing less than 2 mg and/or less than 2% w/w of Fluphenazine Hydrochloride

Use the average of the individual results determined in the test for Uniformity of content.

For tablets containing 2 mg or more and 2% w/w or more of Fluphenazine Hydrochloride

Carry out the following procedure protected from light. Record second-derivative ultraviolet absorption spectra of the following solutions in the range 230 to 300 nm, Appendix II B. For solution (1) add 20 mL of 0.1m hydrochloric acid to 10 tablets, mix with the aid of ultrasound until the tablets are dispersed, add 600 mL of a mixture of 1 volume of 1m hydrochloric acid and 99 volumes of ethanol (80%), shake for 20 minutes, dilute to 1000 mL with the same solvent mixture, mix and filter. Solution (2) contains 0.001% w/v of fluphenazine hydrochloride BPCRS.

For each solution measure the amplitude from the peak at about 266 nm to the trough at about 258 nm. Calculate the content of C22H26F3N3OS,2HCl in the tablets using the declared content of C22H26F3N3OS,2HCl in fluphenazine hydrochloride BPCRS.