title: Quantitation of poloxamers in pharmaceutical formulations using size exclusion chromatography and colorimetric methods.
abstract: Poloxamers have been used as functional excipients in pharmaceutical products. They function as surfactants, emulsifying agents, solubilizing agents, dispersing agents, and in vivo absorbance enhancer. Despite their wide range of applications, limited analytical techniques have been reported in literature for characterizing poloxamers and few are targeted to quantify poloxamer contents in formulations with desired sensitivity and accuracy. In this paper, two distinct analytical methods for quantifying low levels of poloxamers in pharmaceutical formulations have been developed and optimized: a colorimetric method and a size exclusion chromatography method. The colorimetric method is based on the formation of a colored complex between poloxamers and cobalt(II) thiocyanate in aqueous medium, which has a maximum UV absorbance at 624 nm. The feasibility of this method is product specific. In this report, adequate specificity and sensitivity was demonstrated for only one of the several products tested. The size exclusion chromatography (SEC) method utilizes size exclusion columns with THF as mobile phase and refractive index detection. The SEC method provides a limit of quantitation (LOQ) of 0.005 mg/mL (0.0005%, w/w) and at least three orders of magnitudes of linear range. We applied the SEC method to pharmaceutical products containing 0.3-10% poloxamer 188 or poloxamer 407, such as Avapro, Neurontin, Sudafed and other developmental formulations. The results obtained with the SEC method agreed very well with literature and theoretical values with 97-102% recovery. The SEC method was proven to be widely applicable, accurate, precise and simple to use.
authors.affiliation: Pharmaceutical Research & Development, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA. yun.mao@merck.com
authors.forename: Yun
authors.initials: Y
authors.lastname: Mao
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Thompson
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Wang
authors.forename: Eric W
authors.initials: EW
authors.lastname: Tsai
mesh_terms: D000588:Amines / Q000008:administration & dosage; D001713:Biphenyl Compounds / Q000008:administration & dosage; D002850:Chromatography, Gel / Q000379:methods; D003124:Colorimetry / Q000379:methods; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage; D004809:Ephedrine / Q000008:administration & dosage; D000077206:Gabapentin; D000077405:Irbesartan; D015394:Molecular Structure; D020442:Poloxamer / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013607:Tablets / Q000737:chemistry; D013777:Tetrazoles / Q000008:administration & dosage; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage
chemical_list: D000588:Amines; D001713:Biphenyl Compounds; D003509:Cyclohexanecarboxylic Acids; D013607:Tablets; D013777:Tetrazoles; D020442:Poloxamer; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D004809:Ephedrine; D000077405:Irbesartan