Effect of antioxidants and silicates on peroxides in povidone

Journal of Pharmaceutical Sciences

Volumn 101, Issue 1, 2012, Pages 127-139

  Narang, Ajit S ^a   Rao, Venkatramana M ^a   Desai, Divyakant S ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Antioxidants; Excipients; Molecular sieves; Oxidation; Peroxides; Polymers; PVP; Silica; Silicates; Stability

Indexed keywords

ANTIOXIDANT; ASCORBIC ACID; BUTYLATED HYDROXYANISOLE; BUTYLCRESOL; METHANOL; PEROXIDASE; POVIDONE; SILICA GEL; SILICATE; SODIUM SULFITE;

ARTICLE; HUMIDITY;

EID: 82255175009     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.22729     Document Type: Article

References (54)

1. Hartauer KJ, Arbuthnot GN, Baertschi SW, Johnson RA, Luke WD, Pearson NG, Rickard EC, Tingle CA, Tsang PK, Wiens RE. 2000. Influence of peroxide impurities in povidone and crospovidone on the stability of raloxifene hydrochloride in tablets: Identification and control of an oxidative degradation product. Pharm Dev Technol 5(3):303-310.
2. Luo D, Anderson BD. 2006. Kinetics and mechanism for the reaction of cysteine with hydrogen peroxide in amorphous polyvinylpyrrolidone lyophiles. Pharm Res 23(10):2239-2253.
3. Kasraian K, Kuzniar AA, Wilson GG, Wood JA. 1999. Developing an injectable formula containing an oxygen-sensitive drug: A case study of danofloxacin injectable. Pharm Dev Technol 4(4):475-480.
4. Langley NA, Prasad A, Maschke A, Kolter K. 2009. Does PVP Purity Affect API Stability? American Association of Pharmaceutical Scientists (AAPS) Annual Meeting, Los Angeles, California.
5. Ha E, Wang W, Wang YJ. 2002. Peroxide formation in polysorbate 80 and protein stability. J Pharm Sci 91(10):2252-2264.
6. Luo D, Anderson BD. 2008. Application of a two-state kinetic model to the heterogeneous kinetics of reaction between cysteine and hydrogen peroxide in amorphous lyophiles. J Pharm Sci 97(9):3907-3926.
7. Krotz AH, Mehta RC, Hardee GE. 2005. Peroxide-mediated desulfurization of phosphorothioate oligonucleotides and its prevention. J Pharm Sci 94(2):341-352.
8. Ji JA, Borisov O, Ingham E, Ling V, Wang YJ. 2009. Compatibility of a protein topical gel with wound dressings. J Pharm Sci 98(2):595-605.
9. Yarkala S, Amaravadi S, Rao VU, Vijaykumar V, Navalgund SG, Jagdish B. 2009. Role of excipients on N-oxide raloxifene generation from raloxifene-excipients binary mixtures. Chem Pharm Bull 57(10):1174-1177.
10. International Council for Harmonization. 2006. Guidance for Industry: Q3B(R2) Impurities in New Drug Products. (Available at; last accessed August, 2011)
11. Hovorka S, Schoneich C. 2001. Oxidative degradation of pharmaceuticals: Theory, mechanisms and inhibition. J Pharm Sci 90(3):253-269.
12. Tallon MA, Malawer EG, Machnicki NI, Brush PJ, Wu CS, Cullen JP. 2008. The effect of crosslinker structure upon the rate of hydroperoxide formation in dried, crosslinked poly(vinylpyrrolidone). J Appl Polym Sci 107(5):2776-2785.
13. Wasylaschuk WR, Harmon PA, Wagner G, Harman AB, Templeton AC, Xu H, Reed RA. 2007. Evaluation of hydroperoxides in common pharmaceutical excipients. J Pharm Sci 96(1):106-116.
14. Buhler V, Filges U, Schneider T. 2000. Stabilized polyvinylpyrrolidone formulation. BASF A.- G., Ludwigshafen, Germany. US Patent number 6, 592, 900.
15. Fereira PJ, Desjardin MA, Rohloff CM, Berry SA, Zlatkova-Karaslavova ES. 2005. Non-aqueous formulations containing biodegradable polymers and methionine and solvents for removing peroxides and reducing the oxidative degradation of drugs. Durect Corporation, Cupertino, California. 36 pp, cont-in-part of U S Patent Ser No. 814, 826.
16. Ashraf-Khorassani M, Taylor LT, Waterman KC, Narayan P, Brannegan DR, Reid GL. 2005. Purification of pharmaceutical excipients with supercritical fluid extraction. Pharm Dev Technol 10(4):507-516.
17. Kumar V, Kalonia Devendra S. 2006. Removal of peroxides in polyethylene glycols by vacuum drying: Implications in the stability of biotech and pharmaceutical formulations. AAPS PharmSciTech 7(3):62.
18. Buhler V. 2008. Kollidon: Polyvinylpyrrolidone excipients for the pharmaceuticals. BASF Ludwigshafen, Germany. (Available at; last accessed August, 2011).
19. Yue H, Bu X, Huang MH, Young J, Raglione T. 2009. Quantitative determination of trace levels of hydrogen peroxide in crospovidone and a pharmaceutical product using high performance liquid chromatography with coulometric detection. Int J Pharm 375(1-2):33-40.
20. EMD Chemicals. 2010. 16974 ReflectoQuant Peroxide Test Strips. (Available at; last accessed August, 2011).
21. Su S-C, Chou S-S, Chang P-C, Hwang D-F. 2001. Identification of hydrogen peroxide as a causative agent in noodles implicated in food poisoning. J Food Drug Anal 9(4):220-223.
22. O'Brien FEM. 1948. The control of humidity by saturated salt solutions. J Sci Instrum 25:73-76.
23. Fitzpatrick S, McCabe JF, Petts CR, Booth SW. 2002. Effect of moisture on polyvinylpyrrolidone in accelerated stability testing. Int J Pharm 246(1-2):143-151.
24. Buljubasich L, Bluemich B, Stapf S. 2010. Reaction monitoring of hydrogen peroxide decomposition by NMR relaxometry. Chem Eng Sci 65(4):1394-1399.
25. Kanofsky JR. 1990. Quenching of singlet oxygen by human plasma. Photochem Photobiol 51(3):299-303.
26. Xiang T-X, Anderson BD. 2005. Distribution and effect of water content on molecular mobility in poly(vinylpyrrolidone) glasses: A molecular dynamics simulation. Pharm Res 22(8):1205-1214.
27. Sainz-Diaz CI, Iuga C, Vivier-Bunge A, Hernandez-Laguna A. 2008. Quantum mechanical study of adsorption and reactivity of organic free radicals on silicate surfaces of aerosol particles (abstract #GEOC-201). 235th ACS National Meeting; New Orleans, Louisiana; April 6-10, 2008.
28. Burnett RW, Turnbull WT. 1966. Industrial applications of molecular sieves. Br Chem Eng 11(4):261-262.
29. Won CM, Tang S-Y, Strohbeck CL. 1995. Photolytic and oxidative degradation of an antiemetic agent, RG 12915. Int J Pharm 121(1):95-105.
30. Kaufman MJ. 1990. Applications of oxygen polarography to drug stability testing and formulation development: Solution-phase oxidation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res 7(3):289-292.
31. Inchem (International Programme on Chemical Safety). 2005. 2, 6-di-tert-butyl-p-cresol (BHT). (Available at; last accessed August, 2011)
32. Kraybill HR, Dugan LR, Beadle BW, Vibrans FC, Swartz V, Rezabek H. 1949. Butylated hydroxyanisole as an antioxidant for animal fats. J Am Oil Chem Soc 26(9):449-453.
33. Inchem (International Programme on Chemical Safety). 1965. Eighth Report of the Joint FAO/WHO Expert Committee on Food Additives: Specifications for the identity and purity of food additives and their toxicological evaluation: food colours and some antimicrobials and antioxidants. (Available at; last accessed August, 2011).
34. Solvay Chemicals. 2003. Material Safety Data Sheet: Sodium Sulfite. (Available at; last accessed August, 2011).
35. JT Baker 2008. Material Safety Data Sheet: Ascorbic Acid. (Available at; last accessed August, 2011).
36. The United States Pharmacopeial Convention. 2010. Description and Relative Solubility of USP and NF Articles. United States Pharmacopeia-National Formulary (USP 32 - NF 27). Washington, District of Columbia: US Government.
37. Smirnova EG, Lyubimov YI, Malinina TG, Lyubimova EY, Alexandrushkina NI, Vanyushin BF, Kolesova GM, Yaguzhinsky LS. 2002. Ionol (BHT) produces superoxide anion. Biochemistry 67(11):1271-1275.
38. Kahl R, Weinke S, Kappus H. 1990. Comparison of antioxidant and prooxidant activity of various synthetic antioxidants Adv Exp Med Biol 264:283-290.
39. Fukumoto LR, Mazza G. 2000. Assessing antioxidant and prooxidant activities of phenolic compounds. J Agric Food Chem 48(8):3597-3604.
40. EMD Chemicals. 2010. Drying agents-t. h. e. desiccant. (Available at; last accessed August, 2011).
41. Pillai RS, Jasra RV. Computational study for water sorption in AlPO(4)-5 and AlPO(4)-11 molecular sieves. Langmuir 26(3):1755-1764.
42. Burfield DR, Gan G-H, Smithers RH. 1978. Molecular sieves-Desiccants of choice. J Appl Chem Biotechnol 28(1):23-30.
43. Burfield DR, Smithers RH. 1980. Applications of molecular sieves to purification of chloroform and diethyl ether: Selective absorption of ethanol and phosgene. Chem Ind 6:240-241.
44. Dasler W, Bauer CD. 1946. Removal of peroxides from organic solvents. Ind Eng Chem, Anal Ed 18:52-54.
45. Feinstein RN. 1959. Simple method for removal of peroxides from diethyl ether. J Org Chem 24:1172-1173.
46. Saint-Arroman RP, Basset J-M, Lefebvre F, Didillon B. 2005. Well-defined group IV supported catalysts: An efficient way to increase activities in the deperoxidation of cyclohexyl hydroperoxide with environmentally systems. Appl Catal 290(1-2):181-190.
47. Saint-Arroman RP, Didillon B, de Mallmann A, Basset JM, Lefebvre F. 2008. Deperoxidation of cyclohexyl hydroperoxide by silica-supported alkoxo-tantalum complexes. Appl Catal 337(1):78-85.
48. Burfield DR. 1982. Deperoxidation of ethers. A novel application of self-indicating molecular sieves. J Org Chem 47(20):3821-3824.
49. Walling C. 1975. Fenton's reagent revisited. Acc Chem Res 8(4):125-131.
50. Masarwa A, Rachmilovich-Calis S, Meyerstein N, Meyerstein D. 2005. Oxidation of organic substrates in aerated aqueous solutions by the Fenton reagent. Coord Chem Rev 249(17-18):1937-1943.
51. Salem IA, El-Maazawi M, Zaki AB. 2000. Kinetics and mechanisms of decomposition reaction of hydrogen peroxide in presence of metal complexes. Int J Chem Kinet 32(11):643-666.
52. Kibbe AH. 2009. Povidone. In Handbook of pharmaceutical excipients; Rowe RC, Sheskey PJ, Quinn ME, Eds. 6th ed. Chicago, Illinois: American Pharmaceutical Association.
53. Iveson SM, Litster JD, Hapgood K, Ennis BJ. 2001. Nucleation, growth and breakage phenomena in agitated wet granulation processes: A review. Powder Technol 117(1-2):3-39.
54. Danjo K, Kozaki K, Sunada H, Otsuka A. 1994. Influence of the molecular weight of binding agents on the physical properties of granules and tablets. Chem Pharm Bull 42(10):2121-2125.