Cellaburate

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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Cellulose, acetate butanoate;

Cellulose, acetate butyrate;

Acetylbutyrylcellulose;

Cellulose butyrate acetate;

Cellulose acetate butyrate

CAS RN^®: 9004-36-8.

1 DEFINITION

Cellaburate is a reaction product of cellulose, acetic anhydride or acetic acid, and butyric acid or butyric anhydride. It contains NLT 1.0% and NMT 41.0% of acetyl (C₂H₃O) groups, by weight, and NLT 5.0% and NMT 56.0% of butyryl (C₄H₇O) groups, by weight, calculated on the previously dried, acid-free basis.

2 IDENTIFICATION

Change to read:

A. ASPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197F (CN 1-MAY-2020)

Sample solution: Dissolve 150 mg in 1 mL of acetone. Evenly cast 1 drop of the solution on a sodium chloride plate. Heat the plate at 105° for 10 min.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 ACETYL AND BUTYRYL CONTENT

Internal standard solution: 4.6 mg/mL of isovaleric acid in pyridine. Store it in a tightly closed container.

Saponification solution: Place 250 mL of n-propyl alcohol in a 500-mL volumetric flask, add 65.5 g of potassium hydroxide, and mix to dissolve. Dilute with n-propyl alcohol to volume, and mix.

Acid solution: Place 250 mL of n-propyl alcohol in a 500-mL volumetric flask, add 166 mL of hydrochloric acid, and mix. Dilute with n-propyl alcohol to volume, and mix.

Standard solution: Transfer 0.20 g of glacial acetic acid and 0.31 g of butyric acid to a 50-mL volumetric flask. Dilute with Internal standard solution to volume, and mix.

Sample solution: Transfer 0.15 g of Cellaburate, previously dried at 105° for 1 h, into a 25 - mm * 160 - mm test tube. Pipet 10 mL of Internal standard solution into the test tube, and dissolve by stirring and heating at 110° for 30 min. While stirring, add 5 mL of Saponification solution slowly into the tube. Heat at 110° for 10 min. Cool, and add 5 mL of the Acid solution. Mix on a vortex mixer, and allow the precipitate to settle.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm x 30-m fused silica bonded with a 1-µm layer of phase G35

Temperatures

Column: 125°

Injector: 250°

Detector: 250°

Carrier gas: Helium

Flow rate: 8 mL/min

Injection volume: 1 µL

Injection type: Split ratio, 35:1

System suitability

Sample: Standard solution

[NOTE-The relative retention times for acetic acid, butyric acid, and isovaleric acid are about 0.45, 0.85, and 1.00, respectively.]

Suitability requirements

Tailing factor: NMT 1.5 for the butyric acid peak

Relative standard deviation: NMT 3.0%

Calibration

Sample: Standard solution

Number of injections: 3

Calculate the average unit weight response, F_SA, of acetic acid per 10 mL of the Internal standard solution:

F_SA = (W_RA/R_SA) x F₁

W_RA = weight of acetic acid in the Standard solution (g)

R_SA = average peak response ratio of acetic acid to isovaleric acid RSA

F₁ = volume ratio of the Internal standard solution in the Sample solution to that in the Standard solution, 10:50

Similarly, calculate the average unit weight response, FSB of butyric acid per 10 mL of the Internal standard solution:

F_SB = (W_RB/R_SB) x F₁

W_RB = weight of butyric acid in the Standard solution (g)

R_SB = average peak response ratio of butyric acid to isovaleric acid

Analysis

Sample: Upper clear solution from the Sample solution

Calculate the percentage of acetyl in the portion of Cellaburate taken:

Result = [(M_r1/M_r2) x R_UA  x F_SA]/W_U x 100

M_r1 = formula weight of acetyl, 43

M_r2 = formula weight of acetic acid, 60 12

R_UA = peak response ratio of acetic acid to isovaleric acid in the Sample solution

W_U = weight of Cellaburate taken to prepare the Sample solution (g)

Calculate the percentage of butyryl in the portion of Cellaburate taken:

Result = [(M_r3/M_r4) x R_UB x F_SB]/W_U x 100

M_r3 = formula weight of butyryl, 71

M_r4 = formula weight of butyric acid, 88

R_UB = peak response ratio of butyric acid to isovaleric acid in the Sample solution

Acceptance criteria: 1.0%-41.0% of acetyl (C₂H₃O) groups and 5.0%-56.0% of butyryl (C₄H₇O) groups on the previously dried, acid-free basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 LIMIT OF FREE ACID

Indicator solution: In a 1-L volumetric flask dissolve 0.675 g of bromocresol purple in 25 mL of 0.10 N sodium hydroxide. Dilute with water to volume, and mix.

Calibration solutions: Pipet 1, 2, 3, and 4 mL of 0.001 N acetic acid VS into four 100-mL volumetric flasks, respectively. Pipet 4 mL of the Indicator solution into each flask and into an empty 100-mL volumetric flask, and dilute each flask with water to volume to obtain solutions containing 0.0, 0.60, 1.20, 1.80, and 2.40 µg/mL of acetic acid.

Control solution: Place 96 mL of water in a suitable bottle, add a stirring bar, cap the bottle, and stir for 75 min at room temperature. Pipet 4 mL of the Indicator solution into the bottle, and mix.

Sample solution: Transfer 1-2 g of Cellaburate to a bottle, and add 96 mL of water. Add a stirring bar, cap the bottle, and stir for 75 min at room temperature. Pipet 4 mL of the Indicator solution into the bottle, stir to mix, and allow the solid to settle for 2 min.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: Vis

Analytical wavelength: Determine the maximum absorption of the basic form of bromocresol purple in the Calibration at about 589 nm.

Cell: 1 cm

Blank: Water

Calibration: Determine the absorbances of the Calibration solutions. The absorbance difference between the 0.0-µg/mL solution and the other solutions adheres to Beer's law over the range stated in the Calibration solutions. Plot the absorbance difference versus the concentration of the acetic acid, in µg/mL, on linear graph paper, and draw the straight line best fitting the points, including the origin.

Analysis

Samples: Control solution and Sample solution

Pass 10 mL of the Sample solution through a polytef syringe filter that has been presoaked in isopropyl alcohol. Determine the absorbance of the filtered Sample solution. In the same manner, determine the absorbance of the Control solution. Calculate the percentage of free acid, as acetic acid, in the portion of Cellaburate taken:

Result = (V x C_U/W_U)/F x 100

V = total volume of the Sample solution, 100 mL

C_U = concentration of free acid, calculated as acetic acid (µg/mL), based on the absorbance difference between the Control solution and the Sample solution read directly from the calibration plot

W_U = weight of Cellaburate taken to prepare the Sample solution (g)

F = unit conversion, 106 µg/g

[NOTE-If the C_U value is more than 2.8 µg/mL, reduce the sample size by half in the Sample solution, and repeat the determination.]

Acceptance criteria: NMT 0.1%

5 SPECIFIC TESTS

WATER DETERMINATION, Method 1 (921): NMT 5.0%, using a mixture of methylene chloride and methanol (2:1) in place of the methanol solvent

6 ADDITIONAL REQUIREMENTS

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

LABELING: The labeling indicates the nominal percentage ranges of the acetyl and butyryl groups.

USP REFERENCE STANDARDS (11)

USP Cellaburate RS