Tyloxapol

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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Phenol, 4-(1,1,3,3-tetramethylbutyl)-, polymer with formaldehyde and oxirane;

p-(1,1,3,3-Tetramethylbutyl)phenol polymer with ethylene oxide and formaldehyde

CAS RN: 25301-02-4.

1 DEFINITION

Tyloxapol is a nonionic liquid polymer of the alkyl aryl polyether alcohol type. (NOTE-Precautions should be exercised to prevent contact of Tyloxapol with metals.]

2 IDENTIFICATION

Change to read:

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

Analysis: On the undried specimen

Acceptance criteria: Meets the requirements

3 IMPURITIES

RESIDUE ON IGNITION (281): NMT 1.0%

3.1 LIMIT OF ANIONIC DETERGENTS

Standard solution: Transfer 50 mL of water and 1 mL of a solution of sodium lauryl sulfate containing 150 µg/mL to a 125-mL separator.

Sample solution: Mix 20 mL of a solution containing 10 mg/mL of Tyloxapol with 30 mL of water in a 125-mL separator.

Analysis: To both separators add 2 drops of 3 N hydrochloric acid, 1 drop of methylene blue solution (1 in 25), and 25 mL of chloroform.

Shake both separators gently for 2 min, allow to stand for 10 min, and transfer the chloroform layers to individual separators. Wash the chloroform extracts with separate 25-ml portions of water, transfer the chloroform solutions to matched 50-mL color-comparison tubes, and view downward over a white surface.

Acceptance criteria: The chloroform solution from the Sample solution is not darker than that from the Standard solution, corresponding to NMT 0.075% of anionic detergents (as sodium lauryl sulfate).

3.2 LIMIT OF ETHYLENE OXIDE

Standard solution

[CAUTION-Ethylene oxide is toxic and flammable. Prepare in a well-ventilated hood, using great care.]

Transfer 25 mL of dimethylformamide to a 50-mL volumetric flask and weigh. Add 0.5 mL of ethylene oxide. Reweigh to obtain the weight of ethylene oxide by difference. Dilute with dimethylformamide to volume. Dilute a portion of this solution with dimethylformamide to obtain a solution having a concentration of 10 µg/g of ethylene oxide.

Sample solution: Transfer 1 g of Tyloxapol into a glass- stoppered, 5-mL graduated cylinder. Dilute with dimethylformamide to 2.0 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 1.8-m × 2-mm glass column containing 5% phase G16 on support S12

Temperatures

Injection port: 200°

Detector: 250°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 25 mL/min

Injection volume: 3 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 10%

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity of ethylene oxide in the portion of Tyloxapol taken:

Result = (r_u /r_s ) × (C_s /C_u )

r_u = peak response of ethylene oxide from the Sample solution

r_s = peak response of ethylene oxide from the Standard solution

C_s = concentration of ethylene oxide in the Standard solution (µg/mL)

C_u = concentration of Tyloxapol taken in the Sample solution (g/mL)

Acceptance criteria: NMT 10 µg/g

3.3 LIMIT OF FORMALDEHYDE

Diluent: Isopropyl alcohol and water (4 in 10)

Standard solution: Transfer 750 µL of a solution containing 27 µg/mL of formaldehyde to a 25-mL volumetric flask containing 5 mL of Diluent.

Sample solution: Prepare a solution containing 200 mg/mL of Tyloxapol in Diluent. Transfer 500 µL of this solution to a 25-mL volumetric flask containing 5 mL of Diluent.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857),)

Mode: Vis

Analytical wavelength: 520 nm

Cell: 1 cm

Analysis

Samples: Standard solution, Sample solution, and blank

To the Standard solution, the Sample solution, and a blank (prepared by placing 5 mL of Diluent in a 25-mL volumetric flask) add 500 µL of phenylhydrazine hydrochloride solution (7.5 in 100). Mix, and allow to stand for 10 ± 1 min. Add 300 µL of potassium ferricyanide solution (50 mg/mL) to each flask, mix, and allow to stand for 5 min ± 30 s. Then add 2.0 mL of 2.5 N sodium hydroxide to each. Mix, and allow to stand for 4 ± 1 min. Dilute each flask with Diluent to volume, mix, and read the absorbances after 10 ± 3 min.

Acceptance criteria: NMT 0.0075%; the absorbance of the Sample solution does not exceed that of the Standard solution.

3.4 FREE PHENOL

Sample solution: 10 mg/mL

Analysis: To 10 mL of Sample solution add 1 mL of bromine TS, and mix.

Acceptance criteria: No cloudiness or precipitation is observed immediately.

3.5 ABSENCE OF CATIONIC DETERGENTS

Sample solution: 10 mg/mL

Analysis: Place 10 mL of the Sample solution in a glass-stoppered, 50-mL graduated cylinder, and make distinctly alkaline to litmus with sodium carbonate TS (about 1 mL). Add 4 mL of aqueous bromophenol blue solution (0.4 mg/mL), mix, and add 10 mL of a 1-in-10 solvent mixture of ethylene dichloride in toluene. Shake gently, and allow the layers to separate.

Acceptance criteria: No blue color is observed in the organic solvent layer.

4 SPECIFIC TESTS

CLOUD POINT

Sample solution: Transfer 1.0 g of Tyloxapol, previously mixed, to a 150-mL beaker. Add 100.0 mL of water, and mix until dissolved. Warm the solution while mixing.

Analysis: Transient turbidity may be observed as the solution is warmed. Determine the temperature at which the mixture becomes completely turbid.

Acceptance criteria: The cloud point is between 92" and 97",

PH (791),

Sample solution: 50 mg/mL

Acceptance criteria: 4.0-7.0

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Tyloxapol RS