Morphine Sulfate Suppositories
» Morphine Sulfate Suppositories contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O].
suppositories compounded in fatty acid base
Prepare Morphine Sulfate Suppositories in Fatty Acid Base as follows (see Pharmaceutical Compounding—Nonsterile Preparations 
795
):
795): | Morphine Sulfate | 50 mg |
| Silica Gel | 25 mg |
| Fatty Acid Base, a sufficient quantity to make one suppository |
Calibrate the actual molds with the Fatty Acid Base that is used for preparing the Suppositories, and adjust the formula accordingly. Mix thoroughly the Morphine Sulfate and Silica Gel to obtain a uniform powder. Heat the Fatty Acid Base slowly and evenly until melted. Slowly add the powder to the melted base, with stirring. Mix thoroughly, and pour into molds. Cool, trim, and wrap.
Packaging and storage—
Preserve in tight containers, and store in a refrigerator.
Labeling—
Label Suppositories to state that they are Morphine Sulfate Suppositories in a Fatty Acid Base and to state that they are for rectal use only. Label Suppositories to state that they are to be stored in a refrigerator (2
to 8). The label also bears a warning that the Suppositories are a specially formulated strength to be used only by the patient for whom they were prescribed, and that wrappers are to be removed prior to use.
to 8). The label also bears a warning that the Suppositories are a specially formulated strength to be used only by the patient for whom they were prescribed, and that wrappers are to be removed prior to use.
USP Reference standards 11—
11—
USP Morphine Sulfate RS 
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Uniformity of dosage units 905:
meet the requirements for Weight Variation.
905:
meet the requirements for Weight Variation.
Beyond-use date—
Ninety days after the day on which they were compounded.
Compliance assay for suppositories compounded in fatty acid base—
Mobile phase—
Dissolve 5.5 g of sodium 1-heptanesulfonate in 700 mL of water. Add 300 mL of methanol and 10 mL of glacial acetic acid, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Morphine Sulfate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.5 mg per mL. [note—Prepare this solution fresh daily. ]
System suitability preparation—
Prepare a solution in Mobile phase containing, in each mL, about 0.24 mg of USP Morphine Sulfate RS and 0.15 mg of phenol.
Assay preparation—
Transfer 1 Suppository to a 60-mL separator containing 20 mL of chloroform and 20 mL of 0.01 N hydrochloric acid, and shake to dissolve the Suppository. Transfer the chloroform layer to a 250-mL separator. Extract the aqueous layer with a second 20-mL portion of chloroform, and combine the chloroform extracts in the 250-mL separator. Wash the chloroform extracts with two additional 20-mL portions of 0.01 N hydrochloric acid, combine the aqueous layers in a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass this solution through a filter having a 0.45-µm or finer porosity, discarding the first 4 mL of the filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 284-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The column temperature is maintained at 30. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation and the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for phenol and 1.0 for morphine; the resolution, R, between phenol and morphine is not less than 2.0; the tailing factor for the morphine peak is not more than 2.0; and the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 284-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The column temperature is maintained at 30. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation and the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for phenol and 1.0 for morphine; the resolution, R, between phenol and morphine is not less than 2.0; the tailing factor for the morphine peak is not more than 2.0; and the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O] in the Suppository taken by the formula:
(758.83/668.77)(100C)(rU / rS)
in which 758.83 and 668.77 are the molecular weights of morphine sulfate pentahydrate and anhydrous morphine sulfate, respectively; C is the concentration, in mg per mL, of anhydrous morphine sulfate in the Standard preparation, as determined from the concentration of USP Morphine Sulfate RS corrected for moisture content by a titrimetric water determination; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
suppositories compounded in polyethylene glycol base
Prepare Morphine Sulfate Suppositories in Polyethylene Glycol Base as follows (see Pharmaceutical Compounding—Nonsterile Preparations 795):
795):
| Morphine Sulfate | 50 mg |
| Silica Gel | 25 mg |
| Polyethylene Glycol Base, a sufficient quantity to make one suppository |
Calibrate the actual molds with Polyethylene Glycol Base that is used for preparing the Suppositories, and adjust the formula accordingly. Mix thoroughly the Morphine Sulfate and Silica Gel to obtain a uniform powder. Heat the Polyethylene Glycol Base slowly and evenly until melted. Slowly add the powder to the melted base, with stirring. Mix thoroughly, and pour into molds. Cool, trim, and wrap.
Packaging and storage—
Preserve in tight containers, and store in a refrigerator. Do not dispense or store polyethylene glycol–base suppositories in polystyrene containers.
Labeling—
Label Suppositories to state that they are Morphine Sulfate Suppositories in a Polyethylene Glycol Base and to state that they are for rectal use only. Label Suppositories to state that they are to be stored in a refrigerator (2 to 8). The label also bears a warning that the Suppositories are a specially formulated strength to be used only by the patient for whom they were prescribed, and that wrappers are to be removed prior to use.
to 8). The label also bears a warning that the Suppositories are a specially formulated strength to be used only by the patient for whom they were prescribed, and that wrappers are to be removed prior to use.
USP Reference standards 11—
11—
USP Morphine Sulfate RS
Uniformity of dosage units 905:
meet the requirements for Weight Variation.
905:
meet the requirements for Weight Variation.
Beyond-use date—
Ninety days after the day on which they were compounded.
Compliance assay for suppositories compounded in polyethylene glycol base—
Mobile phase, Standard preparation, System suitability preparation, and Chromatographic system—
Proceed as directed in the Compliance assay for suppositories compounded in fatty acid base.
Assay preparation—
Transfer 1 Suppository to a 100-mL volumetric flask, and add about 70 mL of Mobile phase. Sonicate for 15 minutes to dissolve the Suppository, cool, dilute with Mobile phase to volume, and mix. Pass a 10-mL portion of the solution through a filter having a 0.45-µm or finer porosity, discarding the first 4 mL of the filtrate.
Procedure—
Proceed as directed in the Compliance assay for suppositories compounded in fatty acid base. Calculate the quantity, in mg, of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O] in the Suppository taken by the formula:
(758.83/668.77)(100C)(rU / rS)
in which the terms are as defined therein.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Jeanne H. Sun
Assistant Scientific Liaison 1-301-816-3361 |
(CMP2010) Compounding |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3958
Pharmacopeial Forum: Volume No. 28(2) Page 328