Edition: BP 2025 (Ph. Eur. 11.6 update)
Kaolin and Morphine Oral Suspension
DEFINITION
Kaolin and Morphine Mixture is an oral suspension containing 0.00675% w/v Morphine Hydrochloride, 20% w/v of Light
Kaolin or Light Kaolin (Natural) and 5% w/v of Sodium Bicarbonate in a suitable vehicle.
It should be recently prepared unless the kaolin has been sterilised.
The mixture complies with the requirements stated under Oral Liquids and with the following requirements.
Content of sodium bicarbonate, NaHCO3
4.65 to 5.35% w/v.
Content of anhydrous morphine, C17H19NO3
0.0055 to 0.0080% w/v.
IDENTIFICATION
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Centrifuge 10 mL of the preparation, reserving the supernatant liquid. Extract the residue with four 10-mL quantities of a mixture of 38 mL of acetone and 2 mL of 5M ammonia, centrifuging between each extraction, and evaporate the combined extracts on a water bath to about 5 mL. Mix with the reserved supernatant liquid, add 10 mL of 1M sulfuric acid, shake with two 10-mL quantities of chloroform and discard the chloroform. Add sufficient 5M ammonia to make the aqueous solution alkaline to litmus paper, extract with three 10-mL quantities of a mixture of equal volumes of chloroform and ethanol (96%), evaporate to dryness and dissolve the residue in 0.5 mL of ethanol (96%).
(2) 0.10% w/v of morphine hydrochloride.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel.
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, heat at 105° to 110° for 30 minutes, allow to cool and spray with dilute potassium iodobismuthate solution.
MOBILE PHASE
10 volumes of diethylamine, 20 volumes of ethyl acetate and 70 volumes of toluene.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
TESTS
Acid-insoluble matter 13.8 to 18.4% w/w when determined by the following method. To 3 g add 15 mL of water, cautiously add sufficient 2M hydrochloric acid to make the suspension acidic to litmus paper, boil for 5 minutes, replacing the water lost by evaporation, cool and filter the supernatant liquid. Boil the residue with 20 mL of water and 10 mL of 2M hydrochloric acid, cool, filter through the same filter and wash the residue with water until the washings are free from chloride. Dry and ignite the residue to constant weight at red heat.
ASSAY
For sodium bicarbonate
Boil 20 mL with 40 mL of water for 5 minutes, replacing the water lost by evaporation, add 50 mL of ethanol (96%) previously neutralised to methyl red solution and allow to stand for 1 hour. Filter and wash the residue with 100 mL of a mixture of equal volumes of the neutralised ethanol and water. Add 50 mL of 0.5M hydrochloric acid VS to the combined filtrate and washings, boil, cool and titrate the excess of hydrochloric acid with 0.5M sodium hydroxide VS using methyl red solution as indicator. Each mL of 0.5M hydrochloric acid VS is equivalent to 42.00 mg of NaHCO3.
For anhydrous morphine
Centrifuge 25 mL, reserving the supernatant liquid, and extract the residue with three 25-mL quantities of ethanol (96%), centrifuging between each extraction and reserving each supernatant liquid. Add 40 mL of water and 7 mL of 5M ammonia to the combined supernatant liquids and extract the mixture with three 30-mL quantities of chloroform. Gently shake each extract with the same 15 mL of a mixture of 2 volumes of water and 1 volume of ethanol (96%) and discard the aqueous ethanol. Evaporate the combined chloroform solutions just to dryness, warm the residue with 10 mL of 1M hydrochloric acid, cool the solution, which may be slightly cloudy, add sufficient water to produce 50 mL and filter (Whatman No. 42 paper is suitable). To 20 mL of the filtrate add 8 mL of a freshly prepared 1% w/v solution of sodium nitrite, allow to stand in the dark for 15 minutes, add 12 mL of 5M ammonia and sufficient water to produce 50 mL and measure the absorbance of a 4-cm layer at 442 nm without delay, Appendix II B. Use in the reference cell a solution prepared in the same manner but using water in place of the sodium nitrite solution. Calculate the content of anhydrous morphine taking 124 as the value of A(1%, 1 cm) at the maximum at 442 nm.
STORAGE
Kaolin and Morphine Mixture should be kept in well-filled glass containers.
