DOCSLIB.ORG

Journal of Chromatography A, 1599 (2019) 136–143

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Journal of Chromatography A, 1599 (2019) 136–143 Journal of Chromatography A, 1599 (2019) 136–143 Contents lists available at ScienceDirect Journal of Chromatography A jo urnal homepage: www.elsevier.com/locate/chroma Development of a design of experiments optimized method for quantification of polysorbate 80 based on oleic acid using UHPLC-MS a,b,c,∗ b,c a,d Julia Puschmann , Dirk-H. Evers , Christel C. Müller-Goymann , b,c Michael E. Herbig a Institut für Pharmazeutische Technologie, TU Braunschweig, Braunschweig, Germany b Almirall Hermal GmbH, Reinbek, Germany c RaDes GmbH, Hamburg, Germany d Center of Pharmaceutical Engineering (PVZ), TU Braunschweig, Braunschweig, Germany a r a t i c l e i n f o b s t r a c t Article history: The aim was to develop a straightforward UHPLC-MS quantification method for polysorbate 80 using Received 24 December 2018 oleic acid as surrogate marker, which was the commonest substance within the emulsifier. However, Received in revised form 2 April 2019 hydrolysis of polysorbate 80 and subsequent analysis of fatty acids revealed a co-elution of oleic acid Accepted 7 April 2019 and an isomer while all the other fatty acids were successfully separated by varying retention times Available online 8 April 2019 and mass-to-charge ratios. For identification and separation of the isomer a derivatization method was evaluated. Oxidation to the corresponding dihydroxystearic acids with potassium permanganate resulted Keywords: in peak separation of cis/trans and structural isomers of the 18:1 fatty acids. Hydrolyzed and derivatized Polysorbate 80 2 polysorbate 80 was quantified indirectly in the range of 0.046–5.83 ␮g/mL (R > 0.997) with a limit of Design of experiments Quantification detection of 11.4 ng/mL. Quantification of polysorbate 80 using oleic acid as a surrogate marker showed Oleic acid good reproducibility and linearity. As all isomers of the 18:1 fatty acids were successfully separated, the UHPLC-MS previously co-eluting peak was identified as elaidic acid and was found as a component in the mixture of Peak separation the emulsifier polysorbate 80. Additionally, cis-vaccenic acid was separated as a second co-eluting isomer. Cis/trans separation Therefore, derivatization led to successful chromatographical separation of cis/trans and structural 18:1 fatty acid isomers. © 2019 Elsevier B.V. All rights reserved. 1. Introduction from different suppliers were compared [3]. The byproducts of the synthesis such as polyethylene glycol have significant impact on The emulsifier polysorbate 80 is often used in a wide range those properties. Therefore, quantification of emulsifiers in aque- of pharmaceutical formulations such as protein formulations and ous phases is an important aspect for understanding interactions emulsions. In water containing systems, polysorbate 80 is added to within formulations. increase the solubility of active pharmaceutical ingredients (API) So far, the composition of polysorbate 80 regarding the fatty in the aqueous phase [1], typically in a concentration dependent acids is mostly measured via gas chromatography of the methylated manner. As the critical micelle concentration (CMC) is 13 ␮g/mL fatty acids [4,5], which demands the hydrolysis and derivatization [2], quantification of polysorbate 80 is required at concentrations of the emulsifier. To check the usage of state-of-the-art techniques below the CMC for calculations of the impact of micelle-free solu- for analytical methods, they should undergo continuous life-cycle tions on API partitioning. In previous studies, various properties management to ensure the application of the best method for the (CMC, cloud point, micellar molecular weight) of polysorbate 80 task [6]. Keeping this in mind, various methods for polysorbate 80 analysis have been compared. A simple quantification of polysor- bate 80 hydrolyzed to oleic acid is performed with a HPLC and a spectrometric detector [7] but needs 6 h for hydrolysis. Polysor- ∗ Corresponding author at: RaDes GmbH, Schnackenburgallee 114, 22525 Ham- bate 80 can also be quantified by the ethylene oxide chain content burg, Germany. as those chains react with cobalt thiocyanate to a blue complex, E-mail address: [email protected] (J. Puschmann). https://doi.org/10.1016/j.chroma.2019.04.015 0021-9673/© 2019 Elsevier B.V. All rights reserved. J. Puschmann et al. / J. Chromatogr. A 1599 (2019) 136–143 137 which can be detected spectrometrically in concentrations above 2. Material and methods 10 ␮g/mL [8]. As polyethylene glycol is frequently used within pharmaceutical formulations, this method is often not applica- 2.1. Material ble without further calculations as the added polyethylene glycol would undergo the reaction as well. The combinations HPLC-CAD Polysorbate 80 Ph. Eur. quality was supplied by Croda (charged aerosol detector) or HPLC-ELSD (evaporative light scatter- GmbH (Nettetal, Germany, batches: 2607TD1683, 2503TP490, ing detector) also allow quantification of polysorbate 80 as a single 1403UP2005). Acetonitrile LC–MS grade and acetone HPLC grade peak at low concentrations above 5 ␮g/mL [9–12]. The variation of were from Th. Geyer (Renningen, Germany). Ammonium acetate in analysis methods (fluorescence micelle assay, mixed-mode HPLC LC–MS quality was ordered from Promochem (Wesel, Germany). coupled to CAD or ELSD) shows comparable results regarding the Potassium permanganate and sodium hydroxide were ordered content of polysorbate 80 but varies in the detection of degradation from Merck KGaA (Darmstadt, Germany) in Ph. Eur. quality. products [13]. Citrate buffer 0.1 M pH 5 was prepared with citric acid mono- As the mentioned methods are not sufficiently sensitive for hydrate Ph. Eur. quality (Merck KGaA, Darmstadt, Germany), most formulations with rather low polysorbate 80 concentrations, sodium citrate dihydrate Ph. Eur. quality (Biesterfeld AG, Ham- a new method shall be evaluated with a UHPLC coupled to a single burg, Germany) and purified water Ph. Eur. (DEWA Engineering mass spectrometer (QDa) using a surrogate marker. Polysorbate und Anlagenbau GmbH, Vienenburg, Germany). Purified water in 80 consists of mixtures of mono- and diesters of fatty acids and the quality of water for chromatography R (Ph. Eur.) for UHPLC anal- polyethylene glycol chains of different lengths [14–16], resulting ysis was obtained with a Maxima-apparatus from ELGA LabWater in a difficult quantification of the whole molecule as the composi- (Celle, Germany) and purified water in LC–MS quality was ordered tion varies from batch to batch [17]. The European Pharmacopeia from Carl Roth GmbH + Co. KG (Karlsruhe, Germany). (Ph. Eur.) demands a concentration of more than 58% oleic acid [4], The following fatty acids were purchased from Sigma Aldrich therefore, oleic acid is chosen as the marker substance. Within chro- Chemie GmbH (Taufkirchen, Germany): linoleic acid >99%, palmitic matographic analysis, it is important to include a washing step with acid >99%, stearic acid >99%, myristic acid >98%, oleic acid ((Z)- high organic phase concentrations to prevent changes in retention octadec-9-enoic acid) >99%, palmitoleic acid >98.5%, linolenic acid properties of columns [18]. As the European Pharmacopeia also >99%, elaidic acid ((E)-octadec-9-enoic acid) >99%, petroselinic acid describes the presence of further fatty acids (myristic acid, palmitic ((Z)-octadec-6-enoic acid) >99%, cis-vaccenic acid ((Z)-octadec- acid, palmitoleic acid, stearic acid, linoleic acid, linolenic acid) to 11-enoic acid) >97%, trans-vaccenic acid ((E)-octadec-11-enoic a certain degree [4], the separation of those shall be obtained by acid) >99%. Petroselaidic acid ((E)-octadec-6-enoic acid) >99% was using the mass spectrometer to selectively detect them by their ordered from Larodan AB (Solna, Sweden). mass-to-charge (m/z) ratios. During the method development a co-eluting peak with the 2.2. Chromatographic conditions for UHPLC analysis with QDa same m/z as oleic acid was found. For the separation of the proposed detection isomers, silver-ion thin-layer chromatography or HPLC followed by gas chromatography was applied in earlier studies [19–23]. As not The analysis was performed with a UHPLC system (ACQUITY TM TM all isomers were fractionated with this method, the DoE (Design UPLC system, Waters GmbH, Eschborn, Germany) using a BEH of Experiments) approach with UHPLC-MS should be followed. The 1.7 ␮m, 2.1 × 50 mm column (Waters GmbH, Eschborn, Germany). separation of various cis-, trans- and the structural 18:1 fatty acid Eluents were acetonitrile (B) and aqueous ammonium acetate isomers should be performed within one run. Therefore, the deriva- 10 mM (A) at a flowrate of 0.8 mL/min. Injection volume was 10 ␮L tization to UV-detectable substances and separation of structural and injections were performed in triplicate. Peaks were detected isomers according to [24–26] is not considered being sufficient. with a single mass spectrometer (QDa, Waters GmbH, Eschborn, Derivatization through oxidation of oleic acid results in mono- Germany, mass range 30 to 1250 m/z). Negative scan mode with a and dihydroxystearic acids using varying oxidizing agents such as cone voltage of 15 V was used. The sampling rate was 10 points per ozone [27], selenium dioxide/tert-butylhydroperoxide [28], hydro- second. The substances were measured in single ion mode. Cap- gen peroxide [29]. For the method development in this study, a illary voltage was set to -0.5 kV. The probe temperature was held ◦ long-known method for derivatization of double bonds with potas- at 600 C. The gas flows were standardized by Waters GmbH, the sium permanganate according to Lapworth et al. [30] is chosen. As consumption rate of nitrogen was 1200 L/h. The mentioned m/z val- − freezing and heating of fatty acids result in an isomerization from ues represented the loss of a proton [M−H] . The m/z values were: the cis- into the trans-form according to [31,32], the reaction is per- m/z 227.2 (myristic acid), m/z 253.2 (palmitoleic acid), m/z 255.2 formed at room temperature to avoid further transformations.
Load more

Recommended publications
  • Docetaxel Formulation in Polysorbate 80
    American Journal of Pharmacology & Therapeutics Research Article Docetaxel Formulation in Polysorbate 80: A Complex and Sensitive System - Jean-René Authelin1*, Doris Andert2, Lucile Boilait3, Jean-Jacques Nguyen-Huu1, Yan-Yan Zhang4 and Ping Ni1 1Sanofi R&D, 94400 Vitry sur Seine, France 2Sanofi Industrial Affairs, 65926 Frankfurt am Main, Germany 3Sanofi R&D, 34000 Montpellier, France 4Sanofi R&D, 200040 Shanghai, China *Address for Correspondence: Jean-René Authelin, Sanofi R&D, 94400 Vitry sur Seine, France, E-mail: Submitted: 21 September 2020; Approved: 25 September 2020; Published: 30 September 2020 Cite this article: Authelin JR, Andert D, Boilait L, Nguyen-Huu JJ, Zhang YY, Ni P. Docetaxel Formulation in Polysorbate 80: A Complex and Sensitive System. Am J Pharmacol Ther. 2020 Sep 30;4(1): 001-006. doi: 10.37871/ajpt.id19 Copyright: © 2020 Authelin JR, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. American Journal of Pharmacology & Therapeutics ABSTRACT Background: Innovator docetaxel (in Taxotere reference product), a poorly water-soluble agent with a narrow therapeutic index, is developed as a solution in Polysorbate 80 and ethanol. Such formulations form metastable micelles and are considered complex parenterals. Formulation process control impacts quality attributes effi cacy and safety. Characterization of micellar systems in infusion bags is required to ensure good biopharmaceutical performance and equivalence of docetaxel generic formulation. Methods: HPLC, GC, water content (Karl Fischer) and pH were used to characterize chemical properties and oxygen content in the vial headspace.
    [Show full text]
  • Effects of Selected Polysorbate and Sucrose Ester Emulsifiers on the Physicochemical Properties of Astaxanthin Nanodispersions
    Molecules 2013, 18, 768-777; doi:10.3390/molecules18010768 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Effects of Selected Polysorbate and Sucrose Ester Emulsifiers on the Physicochemical Properties of Astaxanthin Nanodispersions Navideh Anarjan 1,2 and Chin Ping Tan 1,* 1 Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; E-Mail: [email protected] 2 Young Researchers and Elites Club, East Azarbaijan Science and Research Branch, Islamic Azad University, 15655/461, Tabriz, Iran * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +603-8946-8418; Fax: +603-8942-3552. Received: 7 December 2012; in revised form: 28 December2012 / Accepted: 31 December 2012 / Published: 9 January 2013 Abstract: The effects of selected nonionic emulsifiers on the physicochemical characteristics of astaxanthin nanodispersions produced by an emulsification/evaporation technique were studied. The emulsifiers used were polysorbates (Polysorbate 20, Polysorbate 40, Polysorbate 60 and Polysorbate 80) and sucrose esters of fatty acids (sucrose laurate, palmitate, stearate and oleate). The mean particle diameters of the nanodispersions ranged from 70 nm to 150 nm, depending on the emulsifier used. In the prepared nanodispersions, the astaxanthin particle diameter decreased with increasing emulsifier hydrophilicity and decreasing carbon number of the fatty acid in the emulsifier structure. Astaxanthin nanodispersions with the smallest particle diameters were produced with Polysorbate 20 and sucrose laurate among the polysorbates and the sucrose esters, respectively. We also found that the Polysorbate 80- and sucrose oleate-stabilized nanodispersions had the highest astaxanthin losses (i.e., the lowest astaxanthin contents in the final products) among the nanodispersions.
    [Show full text]
  • Polysorbate 80
    Pharmacopeial Forum Vol. 35(4) [July±Aug. 2009] STAGE 6 HARMONIZATION 1019 BRIEFING ASSAY • COMPOSITION OF FATTY ACIDS Diluent: 20 g/L sodium hydroxide in methanol Polysorbate 80. The European Pharmacopoeia is the coordi- Saturated sodium chloride solution: Sodium chloride and nating pharmacopeia for the international harmonization of the water (1:2). Before use, decant the solution from any undis- compendial standards for the Polysorbate 80 monograph, as solved substance and filter, if necessary. part of the process of international harmonization of Reference solution A: Prepare 0.50 g of the mixture of cali- monographs and general analytical methods of the European, brating substances with the composition described in Table 1. Japanese, and United States pharmacopeias. The following mon- Dissolve in heptane, and dilute with heptane to 50.0 mL. Reference solution B: Reference solution A in heptane (1 in ograph, which represents the ADOPTION STAGE 6 document, Stage 6 Harmonization is based on the corresponding monograph for Polysorbate 80 10) that was prepared by the European Pharmacopoeia and pub- Reference solution C: Prepare 0.50 g of a mixture of fatty lished in PF 33(5) [Sept.±Oct. 2007]. The European Pharmaco- acid methyl esters, which corresponds to the composition of poeia draft was based in part on comments from the Japanese the substance to be examined. Dissolve in heptane, and dilute Pharmacopoeia and the United States Pharmacopeia in response with heptane to 50.0 mL. [NOTEÐCommercially available mix- to the Provisional Harmonized Text Stage 5A and 5B drafts pre- tures of fatty acid methyl esters may also be used.] pared by the European Pharmacopoeia.
    [Show full text]
  • Synthèse Et Évaluation Pharmacologique D'analogues Préactivés De L'ifosfamide
    Synthèse et évaluation pharmacologique d’analogues préactivés de l’ifosfamide : prodrogues et nanoparticules à visée antitumorale Charles Skarbek To cite this version: Charles Skarbek. Synthèse et évaluation pharmacologique d’analogues préactivés de l’ifosfamide : prodrogues et nanoparticules à visée antitumorale. Pharmacie galénique. Université Paris Saclay (COmUE), 2017. Français. NNT : 2017SACLS247. tel-01618196 HAL Id: tel-01618196 https://tel.archives-ouvertes.fr/tel-01618196 Submitted on 17 Oct 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 2 REMERCIEMENTS Je voudrais exprimer mes remerciements aux membres du jury, aux rapporteurs : les Maitres de Conférences Joseph Ciccolini et Sylvie Bégu, ainsi qu’aux examinateurs : les professeurs Elias Fattal, Thierry Martens et Nathalie Chaput ainsi que les docteurs Alain Herrera et Emilie Roger, d’avoir accepté de juger mon travail de thèse. Je souhaite remercier le Dr Lluis Mir, directeur de l’unité UMR CNRS 8203 pour m’avoir accueilli dans son laboratoire « vectorologie et thérapeutiques anticancéreuses » et de m’avoir permis de réaliser mes travaux de thèse après mon stage de Master 2, au cours desquels j’ai pu développer la formulation des dérivés préactivés de l’ifosfamide et réaliser leur évaluation pharmacologique.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,858,330 Boltri Et Al
    USOO585833OA United States Patent (19) 11 Patent Number: 5,858,330 Boltri et al. (45) Date of Patent: *Jan. 12, 1999 54). PHARMACEUTICAL FORMULATIONS IN 52 U.S. Cl. ............................ 424/45; 424/450; 424/484; FORM OF THIXOTROPIC GEL 424/401; 514/772 58 Field of Search ............................. 424/45, 450, 484; 75 Inventors: Luigi Boltri, Antonietta Coppola; 514/772 Marco Gentile; Gaetano Clavenna, all of Milan, Italy 56) References Cited 73) ASSignee: Dompe' S.p.A., L'Aquila, Italy U.S. PATENT DOCUMENTS * Notice: This patent issued on a continued pros- 4,992.256 2/1991 Skaggs ...................................... 424/45 ecution application filed under 37 CFR 4,996,240 2/1991 Osipow et al.. 1.53(d), and is subject to the twenty year patent term provisions of 35 U.S.C. Primary Examiner Rebecca Cook 154(a)(2). Attorney, Agent, or Firm-Griffin, Butler, Whisenhunt & Szipl, LLP 22 Filed: Mar 18, 1996 The present invention relates to a topical formulation of 30 Foreign Application Priority Data gel-like consistency, but nebulizable by a mechanical pump, containing colloidal Silices as gelifying agent. Mar. 22, 1995 IT Italy ................................. MI95AO568 (51) Int. Cl. .................................................. A61L 9/04 9 Claims, No Drawings 5,858,330 1 2 PHARMACEUTICAL FORMULATIONS IN Surface area from 50 to 400 m/g FORM OF THXOTROPIC GEL Average diameter from 7 to 40 nm. All of these materials give Similar gelification phenomena The present invention relates to a topical formulation of but, Since gelification occurs through adsorption, the Surface gel-like consistency, but nebulizable by mechanical pump, area characteristics become paramount for the choice of the containing colloidal Silices as gelifying agent.
    [Show full text]
  • The Effects of Polysorbate 80 on the Fat Emulsion in Ice Cream Mix: Evidence from Transmission Electron Microscopy Studies
    Food Structure Volume 6 Number 2 Article 11 1987 The Effects of Polysorbate 80 on the Fat Emulsion in Ice Cream Mix: Evidence from Transmission Electron Microscopy Studies H. D. Goff M. Liboff W. K. Jordan J. E. Kinsella Follow this and additional works at: https://digitalcommons.usu.edu/foodmicrostructure Part of the Food Science Commons Recommended Citation Goff, H. D.; Liboff, M.; Jordan, W. K.; and Kinsella, J. E. (1987) "The Effects of Polysorbate 80 on the Fat Emulsion in Ice Cream Mix: Evidence from Transmission Electron Microscopy Studies," Food Structure: Vol. 6 : No. 2 , Article 11. Available at: https://digitalcommons.usu.edu/foodmicrostructure/vol6/iss2/11 This Article is brought to you for free and open access by the Western Dairy Center at DigitalCommons@USU. It has been accepted for inclusion in Food Structure by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. FOOD MICROSTRUCTURE, VoL 6 (1987), pp. 193- 198 0730-54 19/87$3 . 00+- . 00 Scanning Microscopy International , Chicago (AMF O'Hare). IL 60666 USA THE EFFECTS OF POLYSORBATE 80 ON THE FAT EMULSION IN ICE CREAM MIX EVIDENCE FROM TRANSMISSION ELECTRON MICROSCOPY STUDIES H. D. Goff", M. Uboff, W. K. Jordan, and J. E. Kinsella Institute of Food Science, Stocking Hall Cornell University, Ithaca, New York 14853 Introduction Emulsifiers are used in ice cream to produce a dry, smooth Emulsifiers, such as mono- and di -glycerides or textured product with desirable melting properties. They function polyoxyethylene sorbitan esters, are used in ice cream to improve by promoting a partial destabilization of the fat emulsion.
    [Show full text]
  • An Efficient UV-Based Method for the Assessment of Oleic Acid Content in Biotherapeutic Drug Products Containing Polysorbate-80 Robert E
    [ APPLICATION NOTE ] An Efficient UV-Based Method for the Assessment of Oleic Acid Content in Biotherapeutic Drug Products Containing Polysorbate-80 Robert E. Birdsall and Ying Qing Yu Waters Corporation, Milford, MA, USA APPLICATION BENEFITS INTRODUCTION ■■ A robust and sensitive method in the Surfactants such as polyoxyethylene sorbitan monooleate (PS-80) are analysis of PS-80 degradants commonly used in formulated biopharmaceuticals to reduce protein denaturing, aggregation, and surface adsorption to vials and syringes.1 ■■ UV-based workflow that enables rapid deployment in regulated environments While PS-80 plays a critical role in stabilizing drug products, degradation of surfactants in formulated drugs can decrease overall product efficacy ■■ Minimal sample preparation with ability and safety. To this end, characterization, identification, and quantitation to perform high throughput analysis of excipients such as PS-80 must be performed to demonstrate the drug product is safe and efficacious in its formulated state. Due to its non-volatile and UV-inactive nature, direct analysis of PS-80 has resulted in methods that incorporate alternative detection techniques such as evaporative light scattering detection (ELSD).2 Yet, given the ubiquitous nature of UV-based instruments in pharmaceutical labs, methods that can utilize existing equipment would be beneficial. Conveniently, the degradation of PS-80 through radical autoxidation or enzymatic processes results in the cleavage of the hydrophobic ester tail (Figure 1) to produce the UV-active fatty acid, oleic acid.1,3,4 Various extraction techniques of fatty acids from biological matrices have resulted in assays that range in degree of sample preparation required, sensitivity, and reproducibility.3-5 UV-based methods that are robust, sensitive, and can be readily deployed in regulated environments are highly valuable in ensuring product quality and safety.
    [Show full text]
  • Polysorbate 80
    Stage 6 Harmonization Official May 1, 2016 Polysorbate 1 . Table 1 (Continued) Polysorbate 80 Mixture of the Following Composition Portions of the monograph text that are national USP text, Substances (%) and are not part of the harmonized text, are marked Methyl oleate 20 N with symbols ( .N) to specify this fact. Methyl eicosenoate 10 Sorbitan, mono-9-octadecenoate, poly(oxy-1,2-ethanediyl) Methyl behenate 10 derivs., (Z)-; Methyl lignocerate 10 Polyoxyethylene 20 sorbitan monooleate [9005-65-6]. Chromatographic system DEFINITION (See Chromatography 〈621〉, System Suitability.) Polysorbate 80 is a mixture of partial esters of fatty acids, Mode: GC mainly oleic acid, with sorbitol and its anhydrides ethox- Detector: Flame ionization ylated with approximately 20 moles of ethylene oxide for Column: 0.32-mm × 30-m G16 on fused silica; film each mole of sorbitol and sorbitol anhydrides. thickness 0.5 µm Temperatures IDENTIFICATION Injection port: 250° • A. It meets the requirements of the test for Composition Detector: 250° of Fatty Acids. Column: See Table 2. Change to read: Table 2 Hold Time LN LN • . .LNF34B. INFRARED ABSORPTION 〈197F〉 . .LNF34 Initial Tempera- Final at Final Tempera- ture Tempera- Tempera- ASSAY ture Ramp ture ture (°) (°/min) (°) (min) Change to read: 80 10 220 Ð 220 Ð 220 40 • COMPOSITION OF FATTY ACIDS Diluent: 20 g/L of sodium hydroxide in methanol Carrier gas: Helium L .Boron trifluoride±methanol solution: 140 g/L of bo- Linear velocity: 50 cm/s ron trifluoride in methanolLNF34 Injection volume: 1 µL Saturated sodium chloride solution: Sodium chloride System suitability and water (1:2). Before use, decant the solution from Samples: Reference solution A and Reference solution B any undissolved substance and filter, if necessary.
    [Show full text]
  • 2B Excipient Monographs for Injection
    USP Excipient Stakeholder Forum, September 29th 2016 Chinese Manufacturer’s Perspective on Excipient Monograph Specifications for Polysorbate 80 used for Injection LOGO Design of the polysorbate 80 for injection 南京威尔化工有限公司 Nanjing Well Chemical Co.,Ltd Ya Wang About Well Chemical 01 Specialized manufacturer of pharmaceutical excipients in China. All the excipients of Well Chemical have been 02 approved by CFDA. For polysorbate 80, we have pharma grade and for 03 injection grade. Introduction of Polysorbate 80 Definition：Polysorbate 80 is a mixture of partial esters of fatty acids,mainly oleic acid, with sorbitol and its anhydrides ethoxylated with approximately 20 moles of ethylene oxide for each mole of sorbitol and sorbitol anhydrides.（USP-39, NF34） Structure: hydrophilic group lipophilic group Introduction of Polysorbate 80 Actual composition: polysorbate 80 polyoxyethylene(12)isosorbide polyoxyethylene(12)isosorbide monooleate polyoxyethylene(12)isosorbide dioleate polyoxyethylene(24)sorbitan polyoxyethylene(24)sorbitan monooleate polyoxyethylene(24) sorbitan dioleate polyoxyethylene(24)sorbitan trioleate polyoxyethylene(24)sorbitan tetraoleate and so on…………………… Introduction of Polysorbate 80 Widely used in many formulations; Solubilizer-injection, oral solution, topical lotions Emulsifier-ointment, cream, gel Dispersing agent-biological product Introduction of Polysorbate 80 Polysorbate 80 is added as solubilizer in dozens of injections and the proportion ranges from 0.1% to 50%; Typical formulation EPO injection Vitamin k1 injection
    [Show full text]
  • The Effects of Polysorbate-80 and Lecithin on Stable Frozen Dessert
    THE EFFECTS OF POLYSORBATE-80 AND LECITHIN ON STABLE FROZEN DESSERT Linda Chang, Matthew Gerber, Esther Hur, Alyssa Jaakobs, Ginger Jiang, Neeraja Konuthula, Allison Murawski, Jeny Nirappil, Nischay Rege, Christina Sarris, Evelyn Tong, Tian Xia Advisor: Rachel Sandler Assistant: Danielle Cusmano ABSTRACT The texture and richness of an ice cream are wholly dependent on the precise combination of its ingredients. This experiment aimed to determine the effects of various concentrations of two emulsifiers: lecithin and polysorbate-80, and to determine if they had a synergistic effect. It was hypothesized that a 70% polysorbate-80 and 30% lecithin ratio would best meet the desired qualities. After conducting sensory evaluations, it was determined that in the low fat ice cream, the emulsifiers had negligible effect on the taste of the final product. In the light ice cream, the 70% polysorbate-80 and 30% lecithin trial had the best texture and richness. In the regular ice cream, the emulsifier negatively impacted the taste of the sample. INTRODUCTION Food science is the scientific discipline that involves all aspects of food development and production. The study of food science begins with the harvesting of ingredients and ends with the consumption of a food product by the consumer. Food scientists formulate and package food products, study of shelf-life of products, conduct sensory evaluation, and have chemical testing of products. Food science has many connections to other scientific disciplines, including microbiology, chemistry, biochemistry, and chemical engineering. Thus, food scientists require an understanding of the fundamental chemical, biological, and physical properties of each of the materials they work with in order to ensure that they can manufacture a microbiologically safe and chemically shelf stable product for mass consumption [1].
    [Show full text]
  • Productinformation Sigma Prod
    POLYOXYETHYLENE SORBITAN MONOOLEATE ProductInformation Sigma Prod. Nos. P1754, P8074, P0567, and P8466 CAS NUMBER: 9005-65-6 SYNONYMS: Tween 80R 1; polyoxyethylene sorbitol ester; polysorbate 80; PEG (20) sorbitan monooleate PHYSICAL DESCRIPTION:2 HO(C H O) (OC H ) OH Appearance: viscous liquid, 2 4 w 2 4 x clear yellow, sometimes with greenish cast Molecular formula: C H O 3 64 124 26 O CH(OC H ) OH Molecular weight: 13103 2 4 y Specific gravity: 1.07 at 25°C H C (OC2H4) OC (CH2)7 (CH2)7 CH3 z CC HLB value: 15.04 H O H Critical micellar concentration (CMC): 13-15 mg/L4,5 H Viscosity: 400-620 cps at 25°C sum of w, x, y, z = 20 STABILITY / STABILITY AS SUPPLIED: The product is stable for years at room temperature, if protected from oxidation. Over time, particularly at high temperatures, any ether linkage is subject to oxidation to form peroxides. This should be re-evaluated for continued suitability in user application every three to five years. SOLUBILITY / SOLUTION STABILITY: Tween 80 dissolves at 1 mL in 10 mL water to give a clear to slightly hazy faint yellow solution. A 1% solution has pH 5.5-7.2.6 It is reported to be soluble in alcohol, cottonseed oil, corn oil, ethyl acetate, methanol and toluene, but insoluble in mineral oil.3 Solutions are reasonably stable at 2-8°C for short periods. Solutions and the neat liquid may undergo autoxidation over time.7 The product is not sterile. Autoclaving of solutions is generally not advised.
    [Show full text]
  • Polysorbates 20, 60, 65 and 80)
    Original: Japanese Provisional translation Evaluation Report of Food Additives Polysorbates (Polysorbates 20, 60, 65 and 80) June 2007 Food Safety Commission Contents History of deliberation.......................................................................................................1 Members of the Food Safety Commission.........................................................................1 Expert members of the Expert Committee on Food Additives, Food Safety Commission.…………1 Evaluation results on the Health Risk Assessment of Polysorbate 20, Polysorbate 60, Polysorbate 65 and Polysorbate 80 as food additives...................................................................................................2 Summary.............................................................................................................................................. 2 1. Introduction...................................................................................................................................... 3 2. Background...................................................................................................................................... 3 3. Outline of the designation of food additives.................................................................................... 3 4. Name, etc. ........................................................................................................................................ 3 (1) Polysorbate 20 ......................................................................................................................
    [Show full text]