Betadex

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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(C₆H₁₀O₅)₇      1134.98

Beta Cyclodextrin CAS RN: 7585-39-9.

1 DEFINITION

Betadex is a nonreducing cyclic compound composed of seven alpha-(1-4) linked D-glucopyranosyl units. It contains NLT 98.0% and NMT 102.0% of betadex (C₆H₁₀O₅)₇, calculated on the anhydrous basis. OFFICIAL

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K. 197K-A (CN 1-MAY-2020) On undried specimen

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. It meets the requirements of the test for

D.

Sample: 0.2 g

Analysis: Mix the Sample with 2 mL of iodine TS, warm in a water bath to dissolve, and allow to stand at room temperature.

Acceptance criteria: A yellow-brown precipitate is formed.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol and water (7:93)

System suitability solution: 0.5 mg/mL of USP Alpha Cyclodextrin RS, 0.5 mg/mL of USP Beta Cyclodextrin RS, and 0.5 mg/mL of USP

Gamma Cyclodextrin RS

Standard solution: 1.0 mg/mL of USP Beta Cyclodextrin RS

Sample stock solution: Transfer 250 mg of Betadex to a 25-mL volumetric flask, and dissolve in water with the aid of heat if necessary. Cool, and dilute with water to volume.

Sample solution: 1 mg/mL of Betadex, prepared from the Sample stock solution, diluted with water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm × 15-cm; 5-µm packing L1

Temperatures

Column: 30°

Detector: 40°

Flow rate: 1.5 mL/min

Injection volume: 50 µL

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for gamma cyclodextrin, alpha cyclodextrin, and beta cyclodextrin are 0.4, 0.5, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between the gamma cyclodextrin and alpha cyclodextrin peaks

Tailing factor: 0.8-2.0 for the three cyclodextrins

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betadex (C₆H₁₀O₅)₇, in the portion of sample taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution 

C_s = concentration of USP Beta Cyclodextrin RS in the Standard solution (mg/mL)

C_u = concentration of Beta Cyclodextrin in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 LIMIT OF REDUCING SUGARS

Cupric solution: 150 mg/mL of cupric sulfate

Tartrate solution: 25 mg/mL of anhydrous sodium carbonate, 25 mg/mL of potassium sodium tartrate, 20 mg/mL of sodium bicarbonate, and 200 mg/mL of anhydrous sodium sulfate

Cupric-tartaric solution: Immediately before use, mix 1 part of Cupric solution with 25 parts of Tartrate solution.

Ammonium molybdate solution: 100 mg/mL of ammonium molybdate

Disodium arsenate solution: 60 mg/mL of disodium arsenate

Ammonium molybdate reagent: Mix 10 mL of Disodium arsenate solution, 50 mL of Ammonium molybdate solution, and 90 mL of diluted sulfuric acid, and dilute with water to 200 mL.

Sample solution: Transfer 1.0 g of Betadex (as calculated on the anhydrous basis) to a 100-mL volumetric flask. Dissolve in and dilute with water that has been previously boiled and cooled to room temperature to volume, and mix. To 1 mL of this solution add 1 mL of Cupric-tartaric solution. Heat on a water bath for 10 min, then cool to room temperature. Add 10 mL of Ammonium molybdate reagent, and allow to stand for 15 min.

Standard stock solution: 20 mg/L of USP Dextrose RS

Standard solution: Prepare at the same time as the Sample solution. To 1 mL of the Standard stock solution add 1 mL of Cupric-tartaric solution. Heat on a water bath for 10 min, then cool to room temperature. Add 10 mL of Ammonium molybdate reagent, and allow to stand for 15 min.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: Vis

Analytical wavelength: 740 nm

Blank: Water

Analysis

Samples: Sample solution and Standard solution

Acceptance criteria: 0.2%; the absorbance of the Sample solution is NMT that of the Standard solution.

4.3 LIMIT OF LIGHT-ABSORBING IMPURITIES

Sample solution: Transfer 1.0 g of Betadex (as calculated on the anhydrous basis) to a 100-mL volumetric flask. Dissolve in and dilute with water that has been previously boiled and cooled to room temperature to volume. Mix, and pass through a filter of 0.2-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV/Vis

Analytical wavelength: 230-750 nm

Cell: 1 cm

Blank: Water

Analysis

Sample: Sample solution

Acceptance criteria

Absorbance:

NMT 0.10, 230-350 nm

NMT 0.05, 350-750 nm

4.4 RELATED COMPOUNDS

Mobile phase, System suitability solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard solution: 0.05 mg/mL each of USP Alpha Cyclodextrin RS, USP Beta Cyclodextrin RS, and USP Gamma Cyclodextrin RS from the System suitability solution, diluted with water

Sample solution: Use the Sample stock solution from the Assay.

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria

Alpha cyclodextrin: 0.25%; the area of any peak corresponding to alpha cyclodextrin is NMT 0.5 times the area of the corresponding peak from the Standard solution.

Gamma cyclodextrin: 0.25%; the area of any peak corresponding to gamma cyclodextrin is NMT 0.5 times the area of the corresponding peak from the Standard solution.

Other related substances: 0.5%; the sum of all of the peak areas, excluding the alpha cyclodextrin, beta cyclodextrin, gamma cyclodextrin, and artifact peaks is NMT the area of the peak due to betadex (beta cyclodextrin) from the Standard solution.

5 SPECIFIC TESTS

5.1 MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): 

The total aerobic microbial count does not exceed 103 cfu/g, and the total combined molds and yeasts count does not exceed 102 cfu/g. It meets the requirements of the tests for absence of Salmonella species and Escherichia coli.

5.2 OPTICAL ROTATION, Specific Rotation (781S)

Sample solution: 10 mg/mL in water

Acceptance criteria: +160° to +164°, determined at 20°

5.3 WATER DETERMINATION, Method / (921): NMT 14.0%

5.4 COLOR AND CLARITY OF SOLUTION

Sample solution: Dissolve 0.2 g in 20.0 mL of freshly boiled and cooled water.

Acceptance criteria: The resulting solution is clear and colorless.

5.5 PH (791)

Sample solution: Add 0.1 mL of a saturated solution of potassium chloride to 10 mL of a 10 mg/mL aqueous solution of Betadex.

Acceptance criteria: 5.0-8.0

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE: Preserve in tight containers. No storage requirements specified.

6.2 USP REFERENCE STANDARDS (11)

USP Alpha Cyclodextrin RS

USP Beta Cyclodextrin RS

USP Gamma Cyclodextrin RS

USP Dextrose RS