Morphine Sulfate Compounded Suppositories

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Morphine Sulfate Compounded Suppositories contain NLT 90.0% and NMT 110.0% of the labeled amount of morphine sulfate pentahydrate [(C₁₇H₁₉NO₃)₂ · H₂SO₄ · 5H₂O].

Prepare Morphine Sulfate Compounded Suppositories in Fatty Acid Base or Polyethylene Glycol Base as follows (see Pharmaceutical Compounding-Nonsterile Preparations (795)).

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.

2 ASSAY

2.1 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

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 284 nm

Column: 4.6-mm x 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 sulfate are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between phenol and morphine sulfate, System suitability solution

Tailing factor: NMT 2.0 for the morphine sulfate 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 = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) ×100

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution

C_S = concentration of USP Morphine Sulfate RS in the Standard solution (mg/mL) (corrected for moisture content by titrimetric determination)

C_U = nominal concentration of morphine sulfate in the Sample solution (mg/mL)

M_r1 = molecular weight of morphine sulfate pentahydrate, 758.83

M_r2 = molecular weight of anhydrous morphine sulfate, 668.77

Acceptance criteria: 90.0%-110.0%

2.2 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 = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) ×100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Morphine Sulfate RS in the Standard solution (mg/mL) (corrected for moisture content by titrimetric determination) 

C_U = nominal concentration of morphine sulfate in the Sample solution (mg/mL)

M_r1 = molecular weight of morphine sulfate pentahydrate, 758.83

M_r2 = molecular weight of anhydrous morphine sulfate, 668.77

Acceptance criteria: 90.0%-110.0%

3 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements for Weight Variation

4 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.

BEYOND-USE DATE: NMT 90 days after the date on which they were compounded when stored in a refrigerator

LABELING: Label Morphine Sulfate Compounded 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. Label it to state the Beyond-Use Date.

USP REFERENCE STANDARDS (11)

USP Morphine Sulfate RS