Tyloxapol Click to View Image
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 [25301-02-4]. »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. Packaging and storage— Preserve in tight containers. USP Reference standards á11ñ USP Tyloxapol RS. Identification,Infrared Absorption á197Fñ: on undried specimen. Cloud point— Transfer 1.0g of it,previously mixed,to a 150-mLbeaker.Add 100.0mLof water,and mix until solution is effected.Warm the solution while mixing:transient turbidity may be observed as the solution is warmed.Determine the temperature at which the mixture becomes completely turbid:the cloud point is between 92and 97. pHá791ñ: between 4.0and 7.0,in a solution (1in 20). Residue on ignition á281ñ: not more than 1.0%. Free phenol— To 10mLof a solution (1in 100)add 1mLof bromine TS,and mix:no cloudiness or precipitation is observed immediately. Limit of anionic detergents— Mix 20mLof a solution (1in 100)with 30mLof water in a 125-mLseparator.In a second 125-mLseparator mix 50mLof water and 1mLof a solution of sodium lauryl sulfate containing 150µg per mL.To both separators add 2drops of 3Nhydrochloric acid,1drop of methylene blue solution (1in 25),and 25mLof chloroform.Shake both separators gently for 2minutes,allow to stand for 10minutes,and transfer the chloroform layers to individual separators.Wash the chloroform extracts with separate 25-mLportions of water,transfer the chloroform solutions to matched 50-mLcolor-comparison tubes,and view downward over a white surface:the chloroform solution from the Tyloxapol preparation is not darker than that from the sodium lauryl sulfate preparation,corresponding to not more than 0.075%of anionic detergents (as sodium lauryl sulfate). Limit of ethylene oxide— Standard preparation— [Caution—Ethylene oxide is toxic and flammable.Prepare in a well-ventilated hood,using great care.]Transfer 25mLof dimethylformamide to a 50-mLvolumetric flask,and weigh accurately.Add about 0.5mLof ethylene oxide,and mix.Reweigh to obtain the weight of ethylene oxide by difference.Dilute with dimethylformamide to volume,and mix.Dilute a portion of this solution with dimethylformamide to obtain a Standard preparationhaving a known concentration of about 10ppm of ethylene oxide. Test preparation— Transfer 1g of Tyloxapol,accurately weighed,to a glass-stoppered,5-mLgraduated cylinder.Dilute with dimethylformamide to 2.0mL,and mix. Chromatographic system (see Chromatography á621ñ)—The gas chromatograph is equipped with a flame-ionization detector and a 1.8-m ×2-mm glass column containing 5%phase G16on support S12.The injection port is maintained at about 200and the detector at about 250.The column temperature is programmed as follows.The temperature is maintained at 50for 3minutes,then increased to 200at a rate of 25per minute,and held at 200for 5minutes.Helium is used as the carrier gas at a flow rate of about 25mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not greater than 10%. Procedure— Separately inject equal volumes (about 3µL)of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in ppm,of ethylene oxide in the portion of Tyloxapol taken by the formula: 2(C/W)(rU/rS), in which Cis the concentration,in µg per mL,of ethylene oxide in the Standard preparation,Wis the weight,in g,of Tyloxapol taken in the Test preparation,and rUand rSare the ethylene oxide peak responses obtained from the Test preparationand the Standard preparation,respectively:not more than 10ppm of ethylene oxide are found. Limit of formaldehyde Standard preparations— Weigh 2.7g of formaldehyde solution into a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 1.0mLof this solution to a second 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 10.0mLof this second solution to a third 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 750µLof this solution to a 25-mLvolumetric flask containing 5mLof a solution of isopropyl alcohol (4in 10). Test preparation— Transfer 2.0g of Tyloxapol to a 10-mLvolumetric flask,and dissolve in a solution of isopropyl alcohol (4in 10),then dilute with a solution of isopropyl alcohol (4in 10)to volume,and mix.Transfer 500µLof this solution to a 25-mLvolumetric flask containing 5mLof isopropyl alcohol solution (4in 10). Procedure— To the Standard preparation,the Test preparation,and a blank,prepared by placing 5mLof isopropyl alcohol solution (4in 10)in a 25-mLvolumetric flask,add 500µLof phenylhydrazine hydrochloride solution (7.5in 100),mix,and allow to stand for 10±1minutes.Add 300µLof potassium ferricyanide solution (1in 20)to each flask,mix,and allow to stand for 5minutes ±30seconds.Then add 2.0mLof 2.5Nsodium hydroxide to each,mix,and allow to stand for 4±1minutes.Dilute each flask with isopropyl alcohol solution (4in 10)to volume,mix,and after 10±3minutes determine the absorbances of the preparations,in 1-cm cells,at the wavelength of maximum absorbance at about 520nm,with a suitable spectrophotometer,using the blank to set the instrument.The absorbance of the solution from the Test preparationdoes not exceed that of the solution from the Standard preparation,corresponding to not more than 0.0075%of formaldehyde. Absence of cationic detergents— Place 10mLof a solution (1in 100)in a glass-stoppered,50-mLgraduated cylinder,and make distinctly alkaline to litmus with sodium carbonate TS(about 1mL).Add 4mLof aqueous bromophenol blue solution (1in 2500),mix,and add 10mLof a 1in 10solvent mixture of ethylene dichloride in toluene.Shake gently,and allow the layers to separate:no blue color is observed in the organic solvent layer. Organic volatile impurities,Method Iá467ñ: meets the requirements. Auxiliary Information— Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist Expert Committee:(EMC)Excipients:Monograph Content USP28–NF23Page 2002 Phone Number:1-301-816-8330