Budesonide

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

Budesonide is a mixture of two epimeric forms, epimer A (C-22S) and epimer B (C-22R). It contains NLT 40.0% and NMT 51.0% of epimer A, and the sum of both epimers is NLT 98.0% and NMT 102.0% of budesonide (C₂₅H₃₄O₆), calculated on the dried basis.

[Note—Protect all solutions containing Budesonide from light.]

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 25 µg/mL

Medium: Methanol

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Buffer: 0.5 mL of glacial acetic acid in 1 L of water. Adjust with potassium hydroxide to a pH of 3.9.

Mobile phase: Acetonitrile and Buffer (45:55)

Standard solution: 0.06 mg/mL of USP Budesonide RS prepared as follows. Transfer USP Budesonide RS to a suitable volumetric flask, dissolve in acetonitrile equivalent to 30% of the flask volume, and dilute with water to volume.

Sample solution: 0.06 mg/mL of Budesonide prepared as follows. Transfer Budesonide to a suitable volumetric flask, dissolve in acetonitrile equivalent to 30% of the flask volume, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Column temperature: 50°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—The relative retention time for epimer B is 0.96 with respect to epimer A.]

Resolution: NLT 1.2 between the two budesonide epimer peaks

Relative standard deviation: NMT 1.0%, for the sum of the peak areas of the two budesonide epimers

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of budesonide epimer A (C₂₅H₃₄O₆) in the portion of Budesonide taken:

Result = [r_UA/(r_UA + r_UB)] × 100

r_UA = peak area of epimer A from the Sample solution

r_UB = peak area of epimer B from the Sample solution

Calculate the percentage of budesonide (C₂₅H₃₄O₆) in the portion of Budesonide taken:

Result = [(r_UA+ r_UB)/(r_SA + r_SB)] × (C_S/C_U) × 100

r_UA= peak area of epimer A from the Sample solution

r_UB= peak area of epimer B from the Sample solution

r_SA = peak area of epimer A from the Standard solution

r_SB= peak area of epimer B from the Standard solution

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

C_U= concentration of Budesonide in the Sample solution (mg/mL)

Acceptance criteria:

Epimer A: 40.0%–51.0%

Both epimers: 98.0%–102.0% on the dried basis

4 IMPURITIES

Change to read:

Organic Impurities

Solution A: 0.5 mL of glacial acetic acid in 1 L of water. Adjust with potassium hydroxide to a pH of 3.9.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Acetonitrile and water (3:7)

System suitability stock solution A: 0.3 mg/mL of USP Budesonide Related Compound E RS in acetonitrile

System suitability stock solution B: 0.3 mg/mL of USP Budesonide Related Compound G RS in acetonitrile

System suitability stock solution C: 0.3 mg/mL of USP Budesonide Related Compound L RS in acetonitrile

System suitability solution: 0.6 mg/mL of USP Budesonide RS and 3 µg/mL each of USP Budesonide Related Compound E RS, USP Budesonide Related Compound G RS, and USP Budesonide Related Compound L RS in Diluent prepared as follows. Transfer USP Budesonide RS to a suitable volumetric flask and add suitable quantities of System suitability stock solution A, System suitability stock solution B, and System suitability stock solution C. Dilute with acetonitrile equivalent to 30% of the final volume and dilute with water to volume.

Standard stock solution: 0.6 mg/mL of USP Budesonide RS prepared as follows. Transfer USP Budesonide RS to a suitable volumetric flask, dissolve in acetonitrile equivalent to 30% of the flask volume, and dilute with water to volume.

Sensitivity solution: 0.3 μg/mL of USP Budesonide RS in Diluent from the Standard stock solution

Standard solution: 6 µg/mL of USP Budesonide RS in Diluent from the Standard stock solution

Sample solution: 0.6 mg/mL of Budesonide prepared as follows. Transfer Budesonide to a suitable volumetric flask, dissolve in acetonitrile equivalent to 30% of the flask volume, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Temperatures:

Autosampler: 4°

Column: 50°. [Note—The resolution between budesonide related compound E and budesonide related compound L may be improved by lowering the temperature, but to NLT 40°.]

Flow rate: 1.5 mL/min

Injection volume: 50 µL

System suitability

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

[Note—The relative retention times of the two epimers of budesonide are 0.96 (epimer B) and 1.00 (epimer A), respectively.]

Resolution: NLT 1.2 between budesonide related compound E and budesonide related compound L and NLT 3.0 between budesonide epimer A and the first epimer of budesonide related compound G, System suitability solution

Tailing factor: NMT 1.5 for the budesonide epimer B peak, Standard solution

Relative standard deviation: NMT 5.0%, for the sum of the peak areas of the two budesonide epimers, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Budesonide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response of each individual impurity from the Sample solution

r_S= peak response of the sum of budesonide epimers from the Standard solution

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

C_U= concentration of Budesonide in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard peaks that are less than 0.05% of the total peak areas of the budesonide epimers. Disregard peaks eluting after 60 min, which, if present, are due to the change in the gradient.

a 11β,16α,17,21-Tetrahydroxypregna-1,4-diene-3,20-dione.

b 16α,17-[Ethylidenebis(oxy)]-11β,21-dihydroxypregna-1,4-diene-3,20-dione.

c Limit includes both epimers.

d 16α,17-[Butylidenebis(oxy)]-11β-hydroxy-17-(hydroxymethyl)-d-homoandrosta-1,4-diene-3,17a-dione; also known as d-homobudesonide.

e This impurity is to be reported under total unspecified impurities. Do not report it under total specified impurities.

f 16α,17-[1-Methylethylidenebis(oxy)]-11β, 21-dihydroxypregna-1,4-diene-3,20-dione.

g 16α,17-[Butylidenebis(oxy)]-11β-hydroxy-3,20-dioxopregna-1,4-dien-21-al; also known as 21-dehydrobudesonide.

h Also known as 14,15-dehydrobudesonide or budesonide 14-ene.

i Also known as 11-ketobudesonide.

j Also known as 1,2-dihydrobudesonide.

k 16α,17-[Butylidenebis(oxy)]-11β-hydroxypregna-1,4-diene-3,20-dione-21-yl acetate.

l 16α,17-[Butylidenebis(oxy)]-11β,21-dihydroxypregna-1,4-diene-3,20-dione-21-butyrate.

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉:

The total aerobic microbial count is NMT 10³ cfu/g, and the total combined molds and yeast count is NMT 10² cfu/g.

Loss on Drying 〈731〉

Analysis: Dry at 105° to constant weight.

Acceptance criteria: NMT 0.3%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage:

Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Budesonide RS

USP Budesonide Related Compound E RS

16α,17-[Butylidenebis(oxy)]-11β,21-dihydroxypregna-1,4,14-triene-3,20-dione. C₂₅H₃₂O₆ 428.52

USP Budesonide Related Compound G RS

16α,17-[Butylidenebis(oxy)]-11β,21-dihydroxypregna-4-ene-3,20-dione. C₂₅H₃₆O₆ 432.55

USP Budesonide Related Compound L RS

16α,17-[Butylidenebis(oxy)]-21-hydroxypregna-1,4-diene-3,11,20-trione. C₂₅H₃₂O₆ 428.52