Phenoxymethylpenicillin Oral Solution

Penicillin antibacterial.

Phenoxymethylpenicillin Oral Solution is a solution of Phenoxymethylpenicillin Potassium in a suitable flavoured vehicle. It is prepared by dissolving the dry ingredients in the specified volume of Water just before issue for use.

The dry ingredients comply with the requirements for Powders and Granules for Oral Solutions and Suspensions stated under Oral Liquids.

For the following tests prepare the Oral Solution as directed on the label. The solution, examined immediately after preparation unless otherwise indicated, complies with the requirements stated under Oral Liquids and with the following requirements.

When freshly constituted, not more than 120.0% of the stated amount of phenoxymethylpenicillin. When stored at the temperature and for the period stated on the label during which the Oral Solution may be expected to be satisfactory for use, not less than 80.0% of the stated amount of phenoxymethylpenicillin.

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

(1) Dilute a volume of the oral solution containing the equivalent of 0.1 g of phenoxymethylpenicillin to 100 mL with mixed phosphate buffer pH 5.4.

(2) 0.11% w/v of phenoxymethylpenicillin potassium BPCRS in mixed phosphate buffer pH 5.4.

(a) Use a TLC silica gel silanised plate (Merck silanised silica gel 60 plates are suitable).

(b) Use the mobile phase as described below.

(c) Apply 1 µL of each solution.

(d) Develop the plate to 15 cm.

(e) After removal of the plate, allow it to dry in air, spray with 0.1m sodium hydroxide, heat at 50° for 10 minutes, allow to cool and spray with a mixture of 100 volumes of starch mucilage, 6 volumes of glacial acetic acid and 2 volumes of a 1% w/v solution of iodine in a 4% w/v solution of potassium iodide.

20 volumes of acetone and 80 volumes of mixed phosphate buffer pH 5.4.

The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

B. Dilute a volume containing the equivalent of 25 mg of phenoxymethylpenicillin to 20 mL with water. To 10 mL add 0.5 mL of neutral red solution and sufficient 0.01m sodium hydroxide to produce a permanent orange colour and then add 1.0 mL of penicillinase solution. The colour changes rapidly to red.

To a weighed quantity of the oral solution containing the equivalent of 0.125 g of phenoxymethylpenicillin add sufficient water to produce 500 mL and dilute 25 mL to 100 mL with water. Place two 2-mL aliquots of the resulting solution into separate stoppered tubes. To one tube add 10 mL of imidazole-mercury reagent, mix, stopper the tube and immerse in a water bath at 60° for exactly 25 minutes, swirling occasionally. Remove from the water bath and cool rapidly to 20° (solution A). To the second tube add 10 mL of water and mix (solution B). Without delay measure the absorbances of solutions A and B at the maximum at 325 nm, Appendix II B, using in the reference cell a mixture of 2 mL of water and 10 mL of imidazole-mercury reagent for solution A and water for solution B. Calculate the content of C₁₆H₁₈N₂O₅S from the difference between the absorbances of solutions A and B, from the difference obtained by repeating the operation using 0.14 g of phenoxymethylpenicillin potassium BPCRS in place of the oral solution and from the declared content of C₁₆H₁₈N₂O₅S in phenoxymethylpenicillin potassium BPCRS. Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C₁₆H₁₈N₂O₅S, weight in volume.

Repeat the procedure using a portion of the oral solution that has been stored at the temperature and for the period stated on the label during which it may be expected to be satisfactory for use.

The Oral Solution should be stored at the temperature and used within the period stated on the label.

The quantity of active ingredient is stated in terms of the equivalent amount of phenoxymethylpenicillin.