Gamma Cyclodextrin

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)₈ 1297.12

Cyclooctaamylose;

Cyclomaltooctaose CAS RN®: 17465-86-0.

1 DEFINITION

Gamma Cyclodextrin is composed of 8 alpha-(1–4) linked d-glycopyranosyl units. It contains NLT 98.0% and NMT 102.0% of cyclooctaamylose (C₆H₁₀O₅)₈ , calculated on the dried basis.

2 IDENTIFICATION

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

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

C. It meets the requirements of the test for Specific Rotation.

3 ASSAY

3.1 Procedure

Mobile phase: Methanol and water (7:93)

System suitability solution: Prepare an aqueous solution containing 0.5 mg/mL each of USP Alpha Cyclodextrin RS, USP Beta Cyclodextrin RS, and USP Gamma Cyclodextrin RS.

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

Sample stock solution: Transfer 250 mg of Gamma Cyclodextrin 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: 1.0 mg/mL of Gamma Cyclodextrin, prepared from the Sample stock solution

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

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

Temperatures

Detector: 40°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

3.3 System suitability

Sample: System suitability solution

[Note—The relative retention times for gamma cyclodextrin, alfadex, and betadex are 0.8, 1.0, and 1.9, respectively.]

3.4 Suitability requirements

Resolution: NLT 1.5 between the gamma cyclodextrin and alfadex peaks

Tailing factors: 0.8–2.0 for the three cyclodextrins

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of gamma cyclodextrin (C₆H₁₀O₅)₈ in the portion of sample taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of gamma cyclodextrin from the Sample solution

r_S = peak response of gamma cyclodextrin from the Standard solution

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

C_U = concentration of the Sample solution (mg/mL) corrected for water found in Specific Tests, Loss on Drying

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%, determined on a 1.0-g specimen

Related Compounds

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

Standard solution: Transfer 5.0 mL of the System suitability solution into a 50-mL volumetric flask, and dilute with water to volume.

Sample solution: Use the Sample stock solution, prepared as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: For the Sample solution, the areas of any peaks corresponding to alfadex (alpha cyclodextrin) or to betadex (beta cyclodextrin) are not greater than the area of the corresponding peaks in the chromatogram of the Standard solution (0.5%); and the sum of the areas of all the peaks, excluding the principal peak, the peaks corresponding to alfadex or to betadex, and artifact peaks, is not greater than the area of the peak corresponding to gamma cyclodextrin in the chromatogram of the Standard solution (0.5%).

Change to read:

Reducing Substances

Dextrose standard solution: Dissolve an accurately weighed quantity of USP Dextrose RS in water to obtain a solution having a concentration of about 10.0 mg/mL of dextrose. (RB 1-Dec-2024)

Analysis: Transfer a quantity of Gamma Cyclodextrin, equivalent to 1.0 g on the dried basis, to a 500-mL conical flask. Dissolve in 10 mL of water, and add 25 mL of alkaline cupric citrate TS2. Cover the flask with aluminum foil, and boil the solution for 5 min. Cool in an ice bath to room temperature. Add 25 mL of 0.6 N acetic acid, 10 mL of 3 N hydrochloric acid, and 10 mL of 0.1 N iodine solution. [Note-The addition of these solutions must be in the order given.]

Titrate the solution with 0.1 N sodium thiosulfate VS, and determine the endpoint potentiometrically. Perform a blank determination (see Titrimetry 〈541〉, Types of Titrations, Blank Corrections). Calculate the difference in volumes required.

Create a calibration curve by similarly titrating 0.25, 0.5, 0.75, and 1.0 mL of the Dextrose standard solution. Plot the amount, in milligrams, of dextrose in each titrated Dextrose standard solution versus the volume consumed, in milliliters, of 0.1 N sodium thiosulfate VS in the titration, and draw a straight line through the four points. From the line so obtained and the volume of 0.1 N sodium thiosulfate VS required in the titration of Gamma Cyclodextrin, determine the weight, W, in mg, of the reducing substances as dextrose in the portion of Gamma Cyclodextrin taken.

Calculate the percentage of the reducing substances in the portion of Gamma Cyclodextrin taken:

Result = (W/W_G) × F × 100

W = weight of the reducing substances as dextrose in the portion of Gamma Cyclodextrin taken (mg)

W_G  = weight of Gamma Cyclodextrin taken (g)

F = conversion factor, 10−3 g/mg

Acceptance criteria: NMT 0.5%

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: It meets the requirements of the tests for the absence of Salmonella species and Escherichia coli. The total aerobic microbial count does not exceed 1000 cfu/g, and the total combined molds and yeasts count does not exceed 100 cfu/g.

Color and Clarity of Solution

Sample solution: Transfer a quantity of Gamma Cyclodextrin, equivalent to 2.5 g on the dried basis, into a 25-mL volumetric flask, dissolve in and dilute with water that has been previously boiled and cooled to room temperature to volume, and mix.

Analysis: Determine the absorbance of the Sample solution in a 1-cm cell at 420 nm, with a suitable spectrophotometer, after correcting for the blank.

Acceptance criteria: At 420 nm, the absorbance is not greater than 0.20, and the solution is clear.

Change to read:

Loss on Drying 〈731〉

Analysis: Dry a sample at 120° (NF 1-Dec-2024) for 2 h.

Acceptance criteria: NMT 11.0% of its weight

Change to read:

Optical Rotation 〈781S〉, Specific Rotation

Sample solution: 10 mg/mL

Analysis: Proceed as directed in the chapter after ltration of the Sample solution through a membrane filter (nominal pore size of 0.45 μm)1 and measure the specific rotation at 20°. (NF 1-Dec-2024)

Acceptance criteria: +174° to +180°

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at room temperature.

USP Reference Standards 〈11〉

USP Alpha Cyclodextrin RS

USP Beta Cyclodextrin RS

USP Dextrose RS

USP Gamma Cyclodextrin RS