AAPS PharmSciTech

, Volume 19, Issue 1, pp 60–78 | Cite as

Microbial Stability of Pharmaceutical and Cosmetic Products

  • Huy Dao
  • Prit Lakhani
  • Anitha Police
  • Venkataraman Kallakunta
  • Sankar Srinivas Ajjarapu
  • Kai-Wei Wu
  • Pranav Ponkshe
  • Michael A. Repka
  • S. Narasimha MurthyEmail author
Mini-Review Theme: Stability of Pharmaceutical Excipients
Part of the following topical collections:
  1. Theme: Stability of Pharmaceutical Excipients


This review gives a brief overview about microbial contamination in pharmaceutical products. We discuss the distribution and potential sources of microorganisms in different areas, ranging from manufacturing sites, pharmacy stores, hospitals, to the post-market phase. We also discuss the factors that affect microbial contamination in popular dosage forms (e.g., tablets, sterile products, cosmetics). When these products are contaminated, the microorganisms can cause changes. The effects range from mild changes (e.g., discoloration, texture alteration) to severe effects (e.g., changes in activities, toxicity). The most common method for countering microbial contamination is the use of preservatives. We review some frequently used preservatives, and we describe the mechanisms by which microorganisms develop resistance to these preservatives. Finally, because preservatives are inherently toxic, we review the efforts of researchers to utilize water activity and other non-preservative approaches to combat microbial contamination.


Microbial contamination Pharmaceutical products Stability Cosmetics Water activity Preservatives 


  1. 1.
    Denyer SP, Norman A, Sean PG. Hugo and Russell’s pharmaceutical microbiology. Hoboken: John Wiley Sons; 2008.Google Scholar
  2. 2.
    Sandle T. A review of cleanroom microflora: types, trends, and patterns. PDA J Pharm Sci Technol. 2011;65(4):392–403.CrossRefPubMedGoogle Scholar
  3. 3.
    Jimenez L. Microbial contamination control in the pharmaceutical industry, vol. 142. New York: Marcel Dekker; 2004.CrossRefGoogle Scholar
  4. 4.
    Smart R, Spooner DF. Microbiological spoilage in pharmaceuticals and cosmetics. J Soc Cosmet Chem. 1972;23:721–37.Google Scholar
  5. 5.
    Piper P, Mahé Y, Thompson S, Pandjaitan R, Holyoak C, Egner R, et al. The Pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast. EMBO J. 1998;17(15):4257–65.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sandle T. Fungal contamination of pharmaceutical products: a growing menace. Eur Pharm Rev. 2014;19(1):68–71.Google Scholar
  7. 7.
    Bergey’s manual of systematic bacteriology—volume one: the | George Garrity | Springer [Internet]. [cited 2017 May 4] Available from:
  8. 8.
    Grice EA, Kong HH, Renaud G, Young AC, NISC Comparative Sequencing Program, Bouffard GG, et al. A diversity profile of the human skin microbiota. Genome Res. 2008;18(7):1043–50.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Singh P, et al. Fungal contamination of raw materials of some herbal drugs and recommendation of Cinnamomum camphora oil as herbal fungitoxicant. Microb Ecol. 2008;56(3):555–60.CrossRefPubMedGoogle Scholar
  10. 10.
    Limyati DA, Juniar BLL. Jamu Gendong, a kind of traditional medicine in Indonesia: the microbial contamination of its raw materials and endproduct. J Ethnopharmacol. 1998;63(3):201–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Tassaneeyakul W, Razzazi-Fazeli E, Porasuphatana S, Bohm J. Contamination of aflatoxins in herbal medicinal products in Thailand. Mycopathologia. 2004;158:239–44.CrossRefPubMedGoogle Scholar
  12. 12.
    Bahri Najafi R, Ghanadi A, Rahimipour E. Microbial control of some Iranian herbal drugs.Iran J Basic Med Sci 2001;4:1–6.Google Scholar
  13. 13.
    Enayatifard R, Asgarirad H, Kazemi-Sani B. Microbial quality of some herbal solid dosage. Afr J Biotechnol. 2010; 9(11).Google Scholar
  14. 14.
    Obuekwe IF, Eichie F. The presence of microorganisms in some common excipients used in tablet formulation. Acta Pol Pharm. 2006;63:121–5.PubMedGoogle Scholar
  15. 15.
    Bassett DCJ, Stokes KJ, Thomas WRG. Wound infection with Pseudomonas multivorans: a water-borne contaminant of disinfectant solutions. Lancet. 1970;295(7658):1188–91.CrossRefGoogle Scholar
  16. 16.
    Ratajczak M, Kubicka MM, Kamińska D, Sawicka P, Długaszewska J. Microbiological quality of non-sterile pharmaceutical products. Saudi Pharm J. 2015;23(3):303–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Kim KY, Kim YS, Kim D. Distribution characteristics of airborne bacteria and fungi in the general hospitals of Korea. Ind Health. 2010;48(2):236–43.CrossRefPubMedGoogle Scholar
  18. 18.
    Qudiesat K, Abu-Elteen K, Elkarmi A, Hamad M, Abussaud M. Assessment of airborne pathogens in healthcare settings. Afr J Microbiol Res. 2009;3(2):66–76.Google Scholar
  19. 19.
    Okten S, Asan A. Airborne fungi and bacteria in indoor and outdoor environment of the pediatric unit of Edirne government hospital. Environ Monit Assess. 2012;184(3):1739–51.CrossRefPubMedGoogle Scholar
  20. 20.
    Jaffal A. Hospital airborne microbial pollution in a desert country. Environ Int. 1997;23(2):167–72.CrossRefGoogle Scholar
  21. 21.
    Mirhoseini SH, Nikaeen M, Khanahmd H, Hatamzadeh M, Hassanzadeh A. Monitoring of airborne bacteria and aerosols in different wards of hospitals—particle counting usefulness in investigation of airborne bacteria. Ann Agric Environ Med. 2015;22(4):670–3.CrossRefPubMedGoogle Scholar
  22. 22.
    Augustowska M, Dutkiewicz J. Variability of airborne microflora in a hospital ward within a period of one year. Ann Agric Environ Med. 2006;13(1):99–106.PubMedGoogle Scholar
  23. 23.
    Austin PD, Elia M. A systematic review and meta-analysis of the risk of microbial contamination of aseptically prepared doses in different environments. J Pharm Pharm Sci. 2009;12(2):233–42.CrossRefPubMedGoogle Scholar
  24. 24.
    Jimenez L. Microbial diversity in pharmaceutical product recalls and environments. PDA J Pharm Sci Technol. 2007;61(5):383–99.PubMedGoogle Scholar
  25. 25.
    Sutton S, Jimenez L. A review of reported recalls involving microbiological control 2004–2011 with emphasis on FDA considerations of “Objectionable organisms”. Am Pharm Rev. 2012;15(1):42–57.Google Scholar
  26. 26.
    USP antimicrobial effectiveness testing.pdf.Google Scholar
  27. 27.
    Ahearn DG, Doyle SR. Fungi associated with drug recalls and rare disease outbreaks. J Ind Microbiol Biotechnol. 2014;41(11):1591–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Richter SG. Product contamination control: a practical approach to bioburden testing. J Valid Technol. 1999;5:333–6.Google Scholar
  29. 29.
    Sandle T. Pharmaceutical microbiology: essentials for quality assurance and quality control [Internet]. Woodhead Publishing; 2015 [cited 2016 Nov 5]. Available from:
  30. 30.
    Sutton SV, Porter D. Development of the antimicrobial effectiveness test as USP chapter<51>. PDA J Pharm Sci Technol. 2002;56(6):300–11.PubMedGoogle Scholar
  31. 31.
    Chan ES, Zhang Z. Encapsulation of probiotic bacteria Lactobacillus acidophilus by direct compression. Food Bioprod Process. 2002;80(2):78–82.CrossRefGoogle Scholar
  32. 32.
    Plumpton EJ, Gilbert P, Fell JT. The survival of microorganisms during tabletting. Int J Pharm. 1986;30(2–3):241–6.CrossRefGoogle Scholar
  33. 33.
    Fassihi AR, Davies PJ, Parker MS. Effect of punch pressure on the survival of fungal spores during the preparation of tablets from contaminated raw materials. Zentralbl Pharm Pharmakother Lab. 1977;116:1667–271.Google Scholar
  34. 34.
    柳田友道, 三木孝之, 酒井立夫, 堀越勇. Microbiological studies on drugs and their raw materials. I. Experiments on the reduction of microbial contaminants in tablets during processing. Chem Pharm Bull (Tokyo) 1978;26(1):185–190.Google Scholar
  35. 35.
    Ibrahim YK, Olurinola PF. Comparative microbial contamination levels in wet granulation and direct compression methods of tablet production. Pharm Acta Helv. 1990;66(11):298–301.Google Scholar
  36. 36.
    Litster J, Ennis B. Wetting, nucleation and binder distribution. In: The science and engineering of granulation processes [Internet]. Springer; 2004 [cited 2016 Nov 30]. p. 37–74. Available from:
  37. 37.
    Hansuld EM, Briens L, Sayani A, McCann JA. Monitoring quality attributes for high-shear wet granulation with audible acoustic emissions. Powder Technol. 2012;215:117–23.CrossRefGoogle Scholar
  38. 38.
    Snider B, Liang P, Pearson N. Implementation of water-activity testing to replace Karl Fischer water testing. Pharm Technol. 2007;31(2):56.Google Scholar
  39. 39.
    Bos CE, Van Doorne H, Lerk CF. Microbiological stability of tablets stored under tropical conditions. Int J Pharm. 1989;55(2):175–83.CrossRefGoogle Scholar
  40. 40.
    Wallhauser KH. Microbiological aspects on the subject of oral dosage forms. Pharm Ind. 1977;39:491–7.Google Scholar
  41. 41.
    Gerhardt AH. Moisture effects on solid dosage forms—formulation, processing, and stability. J GXP Compliance. 2009;13(1):58–67.Google Scholar
  42. 42.
    Henke S, Holger P. Pack containing pharmaceutical administration forms [Internet]. Google Patents; 2007 [cited 2016 Nov 27] Available from:
  43. 43.
    Meltzer TH, Blakie EW. Filtration in the pharmaceutical industry [Internet]. Marcel Dekker New York; 1987 [cited 2016 Nov 5] Available from:
  44. 44.
    Bradley A, Probert SP, Sinclair CS, Tallentire A. Airborne microbial challenges of blow/fill/seal equipment: a case study. PDA J Pharm Sci Technol. 1991;45(4):187–92.Google Scholar
  45. 45.
    Blanchin A, Chareyron C, Levert Q. The customer behaviour in the men’s cosmetics market. Diss Univ Halmstad Sch Bus Eng [Internet]. 2007 [cited 2016 Nov 30]; Available from:
  46. 46.
    Neza E, Centini M. Microbiologically contaminated and over-preserved cosmetic products according Rapex 2008–2014. Cosmetics. 2016;3(1):3.CrossRefGoogle Scholar
  47. 47.
    Lundov MD, Faurschou A, Matura M, Boman A, Johansen JD, Lidén C, et al. Methylisothiazolinone in rinse-off products causes allergic contact dermatitis: a repeated open-application study. Br J Dermatol. 2015;173(1):115–22.CrossRefPubMedGoogle Scholar
  48. 48.
    Shaqra QMA, Al-Groom RM. Microbiological quality of hair and skin care cosmetics manufactured in Jordan. Int Biodeterior Biodegrad. 2012;69:69–72.CrossRefGoogle Scholar
  49. 49.
    Hugbo PG, Onyekweli AO, Igwe I. Microbial contamination and preservative capacity of some brands of cosmetic creams. Trop J Pharm Res. 2003;2(2):229–34.Google Scholar
  50. 50.
    Bisno AL, Gerber MA, Kaplan EL, Schwartz RH, et al. Diagnosis and management of group A streptococcal pharyngitis: a practice guideline. Clin Infect Dis. 1997;25(3):574–83.CrossRefPubMedGoogle Scholar
  51. 51.
    Elmorsy TH, Hafez EA. Microbial contamination of some cosmetic preparations in Egypt. J Agric Technol. 2016;12(3):567–77.Google Scholar
  52. 52.
    Hosteing S, Meyer N, Waton J, Barbaud A, Bourrain J-L, Raison-Peyron N, et al. Outbreak of contact sensitization to methylisothiazolinone: an analysis of French data from the REVIDAL-GERDA network. Contact Dermatitis. 2014;70(5):262–9.CrossRefPubMedGoogle Scholar
  53. 53.
    Griffin V. Formaldehyde: hazard alert on a possible human carcinogen. Qld Nurse. 1990;9(2):14.PubMedGoogle Scholar
  54. 54.
    Wong S, Street D, Delgado SI, et al. Recalls of foods and cosmetics due to microbial contamination reported to the US Food and Drug Administration. J Food Prot. 2000;63(8):1113–6.CrossRefPubMedGoogle Scholar
  55. 55.
    Behravan J, Bazzaz F, Malaekeh P. Survey of bacteriological contamination of cosmetic creams in Iran (2000). Int J Dermatol. 2005;44(6):482–5.CrossRefPubMedGoogle Scholar
  56. 56.
    Sawynok J. Pharmacological rationale for the clinical use of caffeine. Drugs. 1995;49(1):37–50.CrossRefPubMedGoogle Scholar
  57. 57.
    Hakil M, Denis S, Viniegra-Gonzalez G, Augur C. Degradation and product analysis of caffeine and related dimethylxanthines by filamentous fungi. Enzym Microb Technol. 1998;22(5):355–9.CrossRefGoogle Scholar
  58. 58.
    LeVine DJ. Stable sprayable hydrocortisone product [Internet]. Google Patents; 1980 [cited 2016 Nov 11]. Available from:
  59. 59.
    Cox PH, Sewell BA. The metabolism of steroids by Cladosporium herbarum. J Soc Cosmet Chem. 1968;19:461–7.Google Scholar
  60. 60.
    Calonge N, Petitti DB, DeWitt TG, Gordis L, Gregory KD, Harris R, et al. Aspirin for the prevention of cardiovascular disease. Ann Intern Med. 2009;150(6):396–404.CrossRefGoogle Scholar
  61. 61.
    Grant DJW, Szöcs J d, Wilson JV. Utilization of acetylsalicylic acid as sole carbon source and the induction of its enzymatic hydrolysis by an isolated strain of Acinetobacter lwoffii. J Pharm Pharmacol. 1970;22(6):461–4.CrossRefPubMedGoogle Scholar
  62. 62.
    Long MT, Hopper DJ, Trudgill PW. Atropine metabolism by a Pseudomonas sp.: diauxic growth and oxidation of the products from esterase-mediated cleavage. FEMS Microbiol Lett. 1993;106(1):111–6.CrossRefGoogle Scholar
  63. 63.
    Carlstrom K. Side chain degradation of epimeric 20-hydroxy-4-pregnene-3-ones by Penicillium lilacinium, NRRL 895. Acta Chem Scand. 1970;24:1759–67.CrossRefPubMedGoogle Scholar
  64. 64.
    Harrison LA. Microbial degradation of cellulose polymers used in cosmetics and toiletries. Int J Cosmet Sci. 1987;9(2):73–84.CrossRefPubMedGoogle Scholar
  65. 65.
    Tenenbaum S. Pseudomonads in cosmetics. J Soc Cosmet Chem. 1967;18:797–807.Google Scholar
  66. 66.
    Denyer SP, Baird RM. Guide to microbiological control in pharmaceuticals and medical devices [Internet]. CRC Press; 2006 [cited 2016 Nov 11]. Available from:
  67. 67.
    Sandle T. Antibiotics and preservatives. In: Pharmaceutical microbiology [Internet]. Elsevier; 2016 [cited 2016 Oct 19]. p. 171–83. Available from:
  68. 68.
    Strickley RG, Iwata Q, Wu S, Dahl TC. Pediatric drugs—a review of commercially available oral formulations. J Pharm Sci. 2008;97(5):1731–74.CrossRefPubMedGoogle Scholar
  69. 69.
    Anand SP, Sati N. Artificial preservatives and their harmful effects: looking toward nature for safer alternatives. Int J Pharm Sci Res. 2013;4(7):2496.Google Scholar
  70. 70.
    Marple B. Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions. Otolaryngol Head Neck Surg. 2004;130(1):131–41.CrossRefPubMedGoogle Scholar
  71. 71.
    Meyer BK, Ni A, Hu B, Shi L. Antimicrobial preservative use in parenteral products: past and present. J Pharm Sci. 2007;96(12):3155–67.CrossRefPubMedGoogle Scholar
  72. 72.
    Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29(4):312–34.CrossRefPubMedGoogle Scholar
  73. 73.
    Oni MO, Adeyemo IA, Agbolade JO. Potency of preservatives in selected drug mixtures in Ibadan, Oyo State, Nigeria. [cited 2016 Oct 5]; Available from:
  74. 74.
    Elder, DP, Crowley P. Antimicrobial preservatives part two: choosing a preservative. [cited 2016 Nov 6]; Available from:
  75. 75.
    Hill G. 13 preservation of cosmetics and toiletries. Handb Biocide Preserv Use 1994;349.Google Scholar
  76. 76.
    Soni MG, Carabin IG, Burdock GA. Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol. 2005;43(7):985–1015.CrossRefPubMedGoogle Scholar
  77. 77.
    Prickett PS, Murray HL, Mercer NH. Potentiation of preservatives (parabens) in pharmaceutical formulations by low concentrations of propylene glycol. J Pharm Sci. 1961;50(4):316–20.CrossRefPubMedGoogle Scholar
  78. 78.
    Michalakis GM, Barry EF. Determination of imidurea in cosmetic products by capillary zone electrophoresis and micellar electrokinetic chromatography. J Soc Cosmet Chem. 1994;45:193–202.Google Scholar
  79. 79.
    Marçon F, Moreau V, Helle F, Thiebault N, Djedaïni-Pilard F, Mullié C. β-Alkylated oligomaltosides as new alternative preservatives antimicrobial activity, cytotoxicity and preliminary investigation of their mechanism of action. J Appl Microbiol. 2013;115(4):977–86.PubMedGoogle Scholar
  80. 80.
    Rowe RC, editor. Handbook of pharmaceutical excipients. 6th ed. London: APhA, (PhP) Pharmaceutical Press; 2009. 888 pGoogle Scholar
  81. 81.
    Denyer SP, Hugo WB, Harding VD. The biochemical basis of synergy between the antibacterial agents, chlorocresol and 2-phenylethanol. Int J Pharm. 1986;29(1):29–36.CrossRefGoogle Scholar
  82. 82.
    McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev. 1999;12(1):147–79.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Kokura S, Handa O, Takagi T, Ishikawa T, Naito Y, Yoshikawa T. Silver nanoparticles as a safe preservative for use in cosmetics. Nanomedicine Nanotechnol Biol Med. 2010;6(4):570–4.CrossRefGoogle Scholar
  84. 84.
    Pasquet J, Chevalier Y, Couval E, Bouvier D, Noizet G, Morlière C, et al. Antimicrobial activity of zinc oxide particles on five micro-organisms of the challenge tests related to their physicochemical properties. Int J Pharm. 2014;460(1–2):92–100.CrossRefPubMedGoogle Scholar
  85. 85.
    Pasquet J, Chevalier Y, Couval E, Bouvier D, Bolzinger M-A. Zinc oxide as a new antimicrobial preservative of topical products: interactions with common formulation ingredients. Int J Pharm. 2015;479(1):88–95.CrossRefPubMedGoogle Scholar
  86. 86.
    Epstein SP, Ahdoot M, Marcus E, Asbell PA. Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009;25(2):113–9.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Charnock C. Are multidose over-the-counter artificial tears adequately preserved? Cornea. 2006;25(4):432–7.CrossRefPubMedGoogle Scholar
  88. 88.
    Tu EY. Balancing antimicrobial efficacy and toxicity of currently available topical ophthalmic preservatives. Saudi J Ophthalmol. 2014;28(3):182–7.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Yamazaki S, Nanno M, Kimura T, Suzumura H, Yoshikawa K. Effects of switching to SofZia-preserved travoprost in patients who presented with superficial punctate keratopathy while under treatment with latanoprost. Jpn J Ophthalmol. 2010;54(1):7–14.CrossRefPubMedGoogle Scholar
  90. 90.
    Kahook MY, Noecker RJ. Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofZia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears. Cornea. 2008;27(3):339–43.CrossRefPubMedGoogle Scholar
  91. 91.
    Paimela T, Ryhänen T, Kauppinen A, Marttila L, Salminen A, Kaarniranta K. The preservative polyquaternium-1 increases cytoxicity and NF-kappaB linked inflammation in human corneal epithelial cells. Mol Vis. 2012;18:1189–96.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Furrer P, Mayer JM, Gurny R. Ocular tolerance of preservatives and alternatives. Eur J Pharm Biopharm. 2002;53(3):263–80.CrossRefPubMedGoogle Scholar
  93. 93.
    Ittoop SM, Seibold LK, Kahook MY. Ocular surface disease and the role of preservatives in glaucoma medications [Internet]. 2014; 1:593–597 p. Available from:
  94. 94.
    Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells. Adv Ther. 2010;27(11):837–45.CrossRefPubMedGoogle Scholar
  95. 95.
    Drugs@FDA: FDA approved drug products Travatan Z [Internet]. [cited 2016 Nov 9]. Available from:
  96. 96.
    Drugs@FDA: FDA approved drug products Alphagan P [Internet]. [cited 2016 Nov 9] Available from:
  97. 97.
    Samson RA, Hoekstra ES, Van Oorschot CA, et al. Introduction to food-borne fungi. Utrecht: Centraalbureau voor Schimmelcultures; 1981.Google Scholar
  98. 98.
    Kinderlerer JL, Hatton PV. Fungal metabolites of sorbic acid. Food Addit Contam. 1990;7(5):657–69.CrossRefPubMedGoogle Scholar
  99. 99.
    Piper P, Calderon CO, Hatzixanthis K, Mollapour M. Weak acid adaptation: the stress response that confers yeasts with resistance to organic acid food preservatives. Microbiology. 2001;147(10):2635–42.CrossRefPubMedGoogle Scholar
  100. 100.
    Valkova N, Lépine F, Bollet C, Dupont M, Villemur R. prbA, a gene coding for an esterase hydrolyzing parabens in Enterobacter cloacae and Enterobacter gergoviae strains. J Bacteriol. 2002;184(18):5011–7.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Nielsen H, Engelbrecht J, Brunak S, von Heijne G. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 1997;10(1):1–6.CrossRefPubMedGoogle Scholar
  102. 102.
    Rastogi SC, Schouten A, de Kruijf N, Weijland JW. Contents of methyl-, ethyl-, propyl-, butyl- and benzylparaben in cosmetic products. Contact Dermatitis. 1995;32(1):28–30.CrossRefPubMedGoogle Scholar
  103. 103.
    Davin-Regli A, Chollet R, Bredin J, Chevalier J, Lepine F, Pagès JM. Enterobacter gergoviae and the prevalence of efflux in parabens resistance. J Antimicrob Chemother. 2006;57(4):757–60.CrossRefPubMedGoogle Scholar
  104. 104.
    Baldry MGC. The bactericidal, fungicidal and sporicidal properties of hydrogen peroxide and peracetic acid. J Appl Bacteriol. 1983;54(3):417–23.CrossRefPubMedGoogle Scholar
  105. 105.
    Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007;130(5):797–810.CrossRefPubMedGoogle Scholar
  106. 106.
    Izawa S, Inoue Y, Kimura A. Oxidative stress response in yeast: effect of glutathione on adaptation to hydrogen peroxide stress in Saccharomyces cerevisiae. FEBS Lett. 1995;368(1):73–6.CrossRefPubMedGoogle Scholar
  107. 107.
    Anthony J Fontana. Understanding water activity for reduced microbial testing using USP method <1112>. Available from:
  108. 108.
    Tony Cundell. The role of water activity in the microbial stability of non-sterile pharmaceutical drug products. [Internet]. European Pharmaceutical Review. 2015 [cited 2016 Nov 11] Available from:
  109. 109.
    Papageorgiou S, Varvaresou A, Tsirivas E, Demetzos C. New alternatives to cosmetics preservation. J Cosmet Sci. 2010;61(2):107.PubMedGoogle Scholar
  110. 110.
    Varvaresou A, Papageorgiou S, Tsirivas E, Protopapa E, Kintziou H, Kefala V, et al. Self-preserving cosmetics. Int J Cosmet Sci. 2009;31(3):163–75.CrossRefPubMedGoogle Scholar
  111. 111.
    Tusé D, Mortelmans K, Hokama LA, Selsted ME, Chapoy LL, Quinn MH. Self-preserving multipurpose ophthalmic solutions incorporating a polypeptide antimicrobial [Internet]. Google Patents; 2002 [cited 2016 Oct 11]. Available from:
  112. 112.
    Orth DS, Kabara JJ. Preservative-free and self-preserving cosmetics and drugs application of hurdle technology. Cosmet Toilet. 1998;113(4):51–8.Google Scholar
  113. 113.
    Kabara JJ. Preservative-free and self-preserving cosmetics and drugs: principles and practices [Internet]. CRC Press; 1997 [cited 2016 Oct 11] Available from:
  114. 114.
    Bαρβαρ$\acute\varepsilon$σoυ A, Παπαγε$ømega$ργ$\acuteıota$oυ Σ, Tσ$ıota$ρ$ıota$β$\acute\alpha$ς E u$μ$ıota$oς, Πρ$ømega$τóπαπα EE, K$\acuteıota$ντζ$ıota$oυ E. Self-preserving cosmetics. 2015 [cited 2016 Oct 11]; Available from:
  115. 115.
    Branen AL, Davidson PM. Use of antioxidants in self-preserving cosmetic and drug formulations. Cosmet Sci Technol Ser 1997;159–180.Google Scholar
  116. 116.
    Al-Adham ISI, Khalil E, Al-Hmoud ND, Kierans M, Collier PJ. Microemulsions are membrane-active, antimicrobial, self-preserving systems. J Appl Microbiol. 2000;89(1):32–9.CrossRefPubMedGoogle Scholar
  117. 117.
    Tsao F, Penley A. Aqueous self preserving soft contact lens solution and method [Internet]. Google Patents; 1990 [cited 2016 Oct 11]. Available from:
  118. 118.
    Petersen W. Antimicrobial ingredients for self-preserving cosmetics. Euro Cosmet. 1999;7:28–37.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Huy Dao
    • 1
  • Prit Lakhani
    • 1
  • Anitha Police
    • 1
  • Venkataraman Kallakunta
    • 1
  • Sankar Srinivas Ajjarapu
    • 1
  • Kai-Wei Wu
    • 1
  • Pranav Ponkshe
    • 1
  • Michael A. Repka
    • 1
  • S. Narasimha Murthy
    • 1
    • 2
    Email author
  1. 1.Department of Pharmaceutics and Drug DeliveryUniversity of Mississippi School of PharmacyUniversityUSA
  2. 2.Institute for Drug Delivery and Biomedical ResearchBangaloreIndia

Personalised recommendations