Oxycodone Hydrochloride Extended-Release Tablets

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

Oxycodone hydrochloride Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1- Dec-2021)

3 ASSAY

Change to read:

Procedure

Buffer solution: 7.8 g/L of potassium phosphate, monobasic in water, adjusted with phosphoric acid to a pH of 3.0 Mobile phase: Acetonitrile and Buffer solution (10:90)

Diluent: Acetonitrile and simulated gastric uid TS without enzyme (10:20)

0.85% phosphoric acid: 10 mL/L of phosphoric acid in water

Standard stock solution: 0.9 mg/mL of USP Oxycodone RS in 0.85% phosphoric acid

Standard solution: 0.09 mg/mL of USP Oxycodone RS in Diluent from the Standard stock solution

Sample stock solution: Nominally (L/100) mg/mL of oxycodone hydrochloride where L is the label claim in mg/Tablets. Transfer 10 Tablets into a 1000-mL volumetric flask, and add 900 mL of Diluent. Stir until the Tablets are completely dispersed. Dilute with Diluent to volume. Physically manipulate the Tablets as necessary to ensure complete dispersion within 24 h with stirring in Diluent. Protect this solution from light.

Sample solution: Nominally about 0.1 mg/mL of oxycodone hydrochloride in Diluent from the Sample stock solution. Pass through a suitable filter of 0.45-µm pore size. For Tablets labeled to contain 10 mg, use the Sample stock solution directly.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm. For Identification B, use a diode array detector in the range of 200–350 nm.

Column: 3.0-mm × 25-cm; 5-µm packing L1

Column temperature: 60°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT 1.4 times the retention time of oxycodone

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.7–1.2

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) in the portion of Tablets taken: 

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

r_U = peak response of oxycodone from the Sample solution

r_S = peak response of oxycodone from the Standard solution

C_S = concentration of USP Oxycodone RS in the Standard solution (mg/mL)

C_U = nominal concentration of oxycodone hydrochloride in the Sample solution (mg/mL)

M_r1 = molecular weight of oxycodone hydrochloride, 351.82

M_r2 = molecular weight of oxycodone base, 315.36 (USP 1-Dec-2021)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: Simulated gastric uid TS without enzymes; 900 mL

Apparatus 1: 100 rpm. Include a stainless-steel spring across the underside of the top of each of the baskets to prevent Tablet adhesion to the underside of the top of the baskets during the test.

Times: 1, 4, and 12 h

0.85% phosphoric acid: 10 mL/L of phosphoric acid in water

Mobile phase: Transfer 28.0 g of potassium phosphate, monobasic into a 4-L flask, and dissolve with 3600 mL of water. Adjust with phosphoric acid to a pH of 3.0. Add 400 mL of acetonitrile, and mix.

Standard stock solution: 0.9 mg/mL of USP Oxycodone RS in 0.85% phosphoric acid

Standard solution: Dilute the Standard stock solution with Medium to obtain a solution having a concentration of 0.009 mg/mL of USP Oxycodone RS for Tablets labeled to contain 10, 15, 20, 30, and 40 mg, and 0.063 mg/mL of USP Oxycodone RS for Tablets labeled to contain 60 and 80 mg.

Sample solution: Pass the solution under test through a suitable filter of 1.0- or 10-µm pore size.

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 3.0-mm × 25-cm; 5-µm packing L1

Column temperature: 60°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT 3.7 times the retention time of oxycodone

4.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.7–1.2

Relative standard deviation: NMT 2%

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) in the sample withdrawn from the vessel at each time point (i):

Result_i = (r_U /r_S) × C_S × (M_r1 /M_r2)

r_U = peak response of oxycodone from the Sample solution

r_S = peak response of oxycodone from the Standard solution

C_S = concentration of USP Oxycodone RS in the Standard solution (mg/mL)

M_r1 = molecular weight of oxycodone hydrochloride, 351.82

M_r2 = molecular weight of oxycodone base, 315.36

Calculate the percentage of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) released at each time point (i): 

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V₂ − V_S )] + (C₁ × V_S )} × (1/L) × 100

Result₃ = ({C₃ × [V − (2 × V_S )]} + [(C₂ + C₁ ) × V_S ]) × (1/L) × 100

C_i = concentration of oxycodone hydrochloride in the portion of the sample withdrawn at time point i (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn from the Medium (mL)

Tolerances: See Table 1 for Tablets labeled to contain 10, 15, 20, and 60 mg; see Table 2 for Tablets labeled to contain 30 and 40 mg; see Table 3 for Tablets labeled to contain 80 mg.

Table 1

Table 2

Table 3

The percentages of the labeled amount of oxycodone hydrochloride (C₁₈H₂₁NO₄ · HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2. (USP 1-Dec-2021)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Delete the following:

5.1 Limit of Oxycodone Related Compound B (Oxycodone N-Oxide)

Diluent: 10 mL/L of phosphoric acid in water

Buffer: 6.8 g/L of monobasic potassium phosphate. Add 1.2 mL of triethylamine, and adjust with Diluent to a pH of 3.0 ± 0.1. Mobile phase: Methanol, tert-butyl methyl ether, and Buffer (30:1:170)

Standard solution: 0.18 mg/mL of USP Oxycodone RS and 0.002 mg/mL of USP Oxycodone Related Compound B RS in Diluent. [Note— Prepare fresh daily.]

Sample stock solution: Transfer 10 Tablets into a 500-mL volumetric flask, add 50 mL of Diluent and 50 mL of alcohol, and sonicate for 90 min to extract the active ingredient. Dilute with Diluent to volume.

Sample solution: 0.2 mg/mL of oxycodone hydrochloride from the Sample stock solution in Diluent. Pass a portion of the solution through a suitable filter, and use the filtrate.

5.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 3.9-mm × 30-cm; 10-µm packing L1

Column temperature: 60°

Flow rate: 1.0 mL/min

Injection volume: 50 µL

5.1.2 System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 4.5 between the oxycodone and oxycodone related compound B peaks

Relative standard deviation: NMT 3.0% for oxycodone related compound B

5.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxycodone related compound B in the portion of Tablets taken:

Result = (r_U /r_S) × (C_S /C_U) × 100

r_U = peak area of oxycodone related compound B from the Sample solution

r_S = peak area of oxycodone related compound B from the Standard solution

C_S = concentration of USP Oxycodone Related Compound B RS in the Standard solution (mg/mL)

C_U = nominal concentration of oxycodone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: NMT 1% (USP 1-Dec-2021)

Add the following:

5.2 Organic Impurities

Buffer solution, Mobile phase, Diluent, 0.85% phosphoric acid, Standard stock solution, Sample stock solution, and Sample solution: Prepare as directed in the Assay.

Standard solution: 0.9 μg/mL of USP Oxycodone RS in Diluent from the Standard stock solution

Sensitivity solution: 0.0001 mg/mL of USP Oxycodone RS in Diluent from the Standard solution

System suitability stock solution: 0.1 mg/mL of USP Oxycodone Related Compound B RS in 0.85% Phosphoric acid System suitability solution: 0.9 μg/mL of USP Oxycodone RS and 0.001 mg/mL of USP Oxycodone Related Compound B RS prepared by diluting the System suitability stock solution with the Standard solution

5.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 206 nm

Column: 4.6-mm × 25-cm; 3-µm packing L1

Column temperature: 60°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT 4.5 times the retention time of oxycodone

5.2.2 System suitability

Samples: Standard solution, Sensitivity solution, and System suitability solution

Suitability requirements

Relative standard deviation: NMT 5.0%, Standard solution

Resolution: NLT 8.0 between oxycodone and oxycodone related compound B, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

5.2.3 Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_U /r_S) × (C_S /C_U) × (1/F) × 100

r_U = peak response of each degradation product from the Sample solution

6 rS = peak response of oxycodone from the Standard solution

C_S = concentration of USP Oxycodone RS in the Standard solution (mg/mL)

C_U = nominal concentration of oxycodone hydrochloride in the Sample solution (mg/mL)

F = relative response factor of each degradation product (see Table 4)

Acceptance criteria: See Table 4. The reporting threshold is 0.1%.

Table 4

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store at controlled room temperature. Delete the following:

Labeling: When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.▲ (USP 1-Dec 2021)

USP Reference Standards 〈11〉

USP Oxycodone RS

USP Oxycodone Related Compound B RS

4,5α-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one N-oxide.

C₁₈H₂₁NO₅       331.36