Morphine Sulfate Suppositories
DEFINITION
Morphine Sulfate Suppositories contain NLT 90.0% and NMT 110.0% of the labeled amount of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O].
Prepare Morphine Sulfate Suppositories in Fatty Acid Base or Polyethylene Glycol Base as follows (see Pharmaceutical Compounding—Nonsterile Preparations 
795
).
795).| Morphine Sulfate | 50 mg |
| Silica Gel | 25 mg |
| Fatty Acid Base or Polyethylene Glycol Base, a sufficient quantity to make | 1 suppository |
Calibrate the actual molds with the Base that is used for preparing the Suppositories, and adjust the formula accordingly. Thoroughly mix the Morphine Sulfate and Silica Gel to obtain a uniform powder. Heat the 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.
ASSAY
• Suppositories in Fatty Acid Base
Mobile phase:
Dissolve 5.5 g of sodium 1-heptanesulfonate in 700 mL of water, and add 300 mL of methanol and 10 mL of glacial acetic acid. Filter and degas.
System suitability solution:
0.24 mg/mL of USP Morphine Sulfate RS and 0.15 mg/mL of phenol in Mobile phase
Standard solution:
0.5 mg/mL of USP Morphine Sulfate RS in Mobile phase. Prepare a fresh solution daily.
Sample solution:
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 through a filter of 0.45-µm or finer pore size, discarding the first 4 mL of the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 284 nm
Column:
4.6-mm × 25-cm; packing L1
Column temperature:
30
Flow rate:
1.5 mL/min
Injection volume:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for phenol and morphine are about 0.7 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between phenol and morphine, System suitability solution
Tailing factor:
NMT 2.0 for the morphine peak
Relative standard deviation:
NMT 2.0% for replicate injections, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O] in the Suppository:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of morphine sulfate in the Standard solution (mg/mL) (corrected for moisture content by titrimetric determination) |
| CU | = | = nominal concentration of morphine sulfate in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of morphine sulfate pentahydrate, 758.83 |
| Mr2 | = | = molecular weight of anhydrous morphine sulfate, 668.77 |
Acceptance criteria:
90.0%–110.0%
• Suppositories in Polyethylene Glycol Base
Mobile phase, System suitability solution, Standard solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay for Suppositories in Fatty Acid Base.
Sample solution:
Transfer 1 Suppository to a 100-mL volumetric flask, and add 70 mL of Mobile phase. Sonicate for 15 min to dissolve the Suppository, cool, dilute with Mobile phase to volume, and mix. Pass a 10-mL portion of the solution through a filter of 0.45-µm or finer pore size, discarding the first 4 mL of filtrate.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of morphine sulfate pentahydrate [(C17H19NO3)2·H2SO4·5H2O] in the Suppository:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of morphine sulfate in the Standard solution (mg/mL) (corrected for moisture content by titrimetric determination) |
| CU | = | = nominal concentration of morphine sulfate in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of morphine sulfate pentahydrate, 758.83 |
| Mr2 | = | = molecular weight of anhydrous morphine sulfate, 668.77 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Uniformity of Dosage Units 905:
Meet the requirements for Weight Variation
905:
Meet the requirements for Weight Variation
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Package in tight containers, and store in a refrigerator. Do not dispense or store Polyethylene Glycol Base Suppositories in polystyrene containers.
• Labeling:
Label Morphine Sulfate Suppositories to state whether they are in a Fatty Acid Base or in a Polyethylene Glycol Base. Label to indicate that they are for rectal use only. Label to state that they are to be stored in a refrigerator. 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 before use.
• Beyond-Use Date:
NMT 90 days after the date on which they were compounded
• USP Reference Standards 11
11
USP Morphine Sulfate RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Jeanne H. Sun, Pharm.D.
Associate Scientific Liaison (301) 230-3361 |
(CMP2010) Compounding |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP38–NF33 Page 4452
Pharmacopeial Forum: Volume No. 40(6)