Login Register Cart 0
Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Preservatives in Pharmaceuticals: Are They Really Safe?

Author(s): Mohit Kumar, Shruti Chopra, Uttam Kumar Mandal* and Amit Bhatia*

Volume 18, Issue 4, 2023

Published on: 12 October, 2022

Page: [440 - 447] Pages: 8

DOI: 10.2174/1574886317666220919121532

Price: $65

Abstract

Preservatives are the ingredients that are utilized in order to improve the shelf life of products (Medicines, food). These tend to slow down or stop the degradation or decomposition processes, therefore, enhance the shelf life of the products. These agents either interfere with the chemical reaction or check the growth of microorganisms in the products. Preservatives are classified according to the mode of action or source or chemical nature. The preservation efficacy can be affected by various factors, e.g., interaction with other components, nature of preservatives, type of containers, type of micro-organism, and pH. Despite being vital for various types of products, these chemicals are not safe, if not used appropriately. The review will provide an updated detail of different types of preservatives along with their safety aspect. This review also highlighted the maximum safe concentration of preservatives that can be required to develop a formulation with maximum safety and low toxicity.

Keywords: Preservatives, parabens, preservative, efficacy, shelf life, safety.

« Previous Next »
[1]
Rajeev B, Abd Karim A, Gopinadhan P, Eds. Progress in food preservation. John Wiley & Sons: Chichester 2012.
[http://dx.doi.org/10.1002/9781119962045]
[2]
Msagati TAM. The chemistry of food additives and preservatives. John Wiley & Sons: Hoboken 2012.
[http://dx.doi.org/10.1002/9781118274132]
[3]
Dalton L. Food preserves. Chem Eng News 2002; 80(45): 40.
[http://dx.doi.org/10.1021/cen-v080n045.p040]
[4]
Chiori CO, Ghobashy AA. A potentiating effect of EDTA on the bactericidal activity of lower concentrations of ethanol. Int J Pharm 1983; 17(2-3): 121-8.
[http://dx.doi.org/10.1016/0378-5173(83)90025-X]
[5]
Nair MS, Nair DVT, Johny AK, Venkitanarayanan K. Use of food preservatives and additives in meat and their detection techniques. In: Meat quality analysis. Elsevier: Amsterdam 2020; pp. 187-213.
[http://dx.doi.org/10.1016/B978-0-12-819233-7.00012-4]
[6]
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.
[http://dx.doi.org/10.1002/jps.2600500409] [PMID: 13737987]
[7]
Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther 2001; 18(5): 205-15.
[http://dx.doi.org/10.1007/BF02853166] [PMID: 11783457]
[8]
Nielsen PB, Müllertz A, Norling T, Kristensen HG. The effect of α-tocopherol on the in vitro solubilisation of lipophilic drugs. Int J Pharm 2001; 222(2): 217-24.
[http://dx.doi.org/10.1016/S0378-5173(01)00701-3] [PMID: 11427352]
[9]
Shitole S, Shinde S, Waghmare S, Kamble H. A review on: Preservatives used in pharmaceuticals and impacts on health. IRE J 2022; 5(7): 131-40.
[10]
Hammad MA, Müller BW. Solubility and stability of tetrazepam in mixed micelles. Eur J Pharm Sci 1998; 7(1): 49-55.
[http://dx.doi.org/10.1016/S0928-0987(98)00006-2] [PMID: 9845777]
[11]
Constantinides PP, Tustian A, Kessler DR. Tocol emulsions for drug solubilization and parenteral delivery. Adv Drug Deliv Rev 2004; 56(9): 1243-55.
[http://dx.doi.org/10.1016/j.addr.2003.12.005] [PMID: 15109767]
[12]
Komatsu E, Yamazaki H, Abe K, et al. Influence of temperature on the efficacy of 2-phenoxyethanol as a preservative for adsorbed diphtheria-purified pertussis-tetanus combined vaccine. J Health Sci 2002; 48(1): 89-92.
[http://dx.doi.org/10.1248/jhs.48.89]
[13]
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.
[http://dx.doi.org/10.1002/jps.20976] [PMID: 17722087]
[14]
Scott VWS. Antimicrobial preservative efficacy and microbial content testing. In: Cosmetic Microbiology. (2nd ed.). CRC Press: Florida 2006; p. 36.
[15]
Al-Hiti , Mustafa MA. Influence of inoculum history upon the reproducibility and predictivity of tests for preservative efficacy. PhD Thesis The University of Manchester 1982.
[16]
Johnson R, Steer R. Methylparaben monograph. In: Handbook of Pharmaceutical Excipients. (5th ed.). Pharmaceutical Press 2006; pp. 466-70.
[17]
Garner N, Siol A, Eilks I. Parabens as preservatives in personal care products. Chem Action 2014; 103: 36-43.
[18]
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.
[http://dx.doi.org/10.1002/jps.21101] [PMID: 17823956]
[19]
Rowe RC, Sheskey PJ, Weller PJ. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: London 2006.
[20]
García MR, Cabo ML. Optimization of E. coli inactivation by benzalkonium chloride reveals the importance of quantifying the inoculum effect on chemical disinfection. Front Microbiol 2018; 9: 1259.
[http://dx.doi.org/10.3389/fmicb.2018.01259] [PMID: 29997577]
[21]
Daniels R, Knie U. Galenics of dermal products? vehicles, properties and drug release. J Dtsch Dermatol Ges 2007; 5(5): 367-83.
[http://dx.doi.org/10.1111/j.1610-0387.2007.06321.x] [PMID: 17451381]
[22]
Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. (6th eds..). Pharmaceutical Press: London 2009; pp. 506-9.
[23]
Pastorova I, de Koster CG, Boon JJ. Analytical study of free and Ester bound benzoic and cinnamic acids of gum benzoin resins by GC–MS and HPLC–frit FAB–MS. Phytochem Anal 1997; 8(2): 63-73.
[http://dx.doi.org/10.1002/(SICI)1099-1565(199703)8:2<63::AIDPCA337>3.0.CO;2-Y.]
[24]
Furrer P, Mayer JM, Gurny R. Ocular tolerance of preservatives and alternatives. Eur J Pharm Biopharm 2002; 53(3): 263-80.
[http://dx.doi.org/10.1016/S0939-6411(01)00246-6] [PMID: 11976014]
[25]
Cahill E. Benzyl alcohol monograph. Handbook of pharmaceutical excipients. Pharmaceutical Press 2006.
[26]
Dodov MG, Goracinova K, Simonoska M, Trajkovic-Jolevska S, Ribarska JT, Mitevska MD. Formulation and evaluation of diazepam hydrogel for rectal administration. Acta Pharm 2005; 55(3): 251-61.
[PMID: 16375836]
[27]
Owen SC. Cetrimide monograph. In: Rowe RC, Sheskey PJ, Weller PJ, Eds. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: Londaon. 2006; pp. 152-4.
[28]
Kasper K, Kremling C, Geerling G. Toxicity of a new moistening agent and preservative in vitro. Ophthalmologe 2008; 105(6): 557-62.
[http://dx.doi.org/10.1007/s00347-007-1640-8] [PMID: 18214492]
[29]
Smock E, Demertzi E, Abdolrasouli A, Azadian B, Williams G. Antiseptic efficacy of povidone iodine and chlorhexidine gluconate skin preparation solutions used in burns surgery. In: J Burn Care Res 2018; 39(3): 440-4.
[PMID: 29897541]
[30]
Burstein NL. Preservative alteration of corneal permeability in humans and rabbits. Invest Ophthalmol Vis Sci 1984; 25(12): 1453-7.
[PMID: 6511230]
[31]
Leikin JB, Paloucek FP, Eds. Chlorhexidine gluconate. Poisoning and Toxicology Handbook. CRC Press: Florida 2007; p. 1378.
[32]
Nema S. Chlorocresol monograph. In: Rowe RC, Sheskey PJ, Weller PJ, Eds. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: Florida 2006; pp. 171-3.
[33]
Bloomfield MS, Prebble KA. The determination of the preservative, chlorocresol, in a pharmaceutical formulation by flow injection analysis. J Pharm Biomed Anal 1992; 10(10-12): 775-8.
[http://dx.doi.org/10.1016/0731-7085(91)80079-O] [PMID: 1298382]
[34]
Jassim ZE, Al-Akkam EJ. A review on strategies for improving nasal drug delivery systems. Drug Invent Today 2018; 2: 10.
[35]
Mcindoe LME. Chloroxylenol monograph. In: Rowe RC, Sheskey PJ, Weller PJ, Eds. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: London 2006.
[36]
Wilson M, Mowad C. Chloroxylenol. Dermatitis 2007; 18(2): 120-1.
[PMID: 17498419]
[37]
Amidon GE. Propionic acid monograph. In: Rowe RC, Sheskey PJ, Weller PJ, Eds. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: London 2006.
[38]
Galichet LY. m-Cresol monograph In: Rowe RC, Sheskey PJ, Weller PJ, Eds. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: London. 2006.
[39]
Benesch R, Benesch RE. Polarographic studies of organic mercury compounds. J Am Chem Soc 1951; 73(7): 3391-6.
[http://dx.doi.org/10.1021/ja01151a115]
[40]
Weller PJ. Thimerosal monograph. In: Rowe RC, Sheskey PJ, Weller PJ, Eds. Handbook of Pharmaceutical Excipients. Pharmaceutical Press: London 2006.
[41]
Khandke L, Yang C, Krylova K, Jansen KU, Rashidbaigi A. Preservative of choice for Prev(e)nar 13™ in a multi-dose formulation. Vaccine 2011; 29(41): 7144-53.
[http://dx.doi.org/10.1016/j.vaccine.2011.05.074] [PMID: 21651942]
[42]
Soni MG, Burdock GA, Taylor SL, Greenberg NA. Safety assessment of propyl paraben: A review of the published literature. Food Chem Toxicol 2001; 39(6): 513-32.
[http://dx.doi.org/10.1016/S0278-6915(00)00162-9] [PMID: 11346481]
[43]
Matthews C, Davidson J, Bauer E, Morrison JL, Richardson AP. PHydroxybenzoic acid esters as preservatives. II. Acute and chronic toxicity in dogs, rats, and mice. J Am Pharm Assoc 1956; 45(4): 260-7.
[http://dx.doi.org/10.1002/jps.3030450420] [PMID: 13319106]
[44]
Sado I. Synergistic toxicity of official permissible preservative food additives. Nippon Eiseigaku Zasshi Jpn J Hyg 1973; 28(5): 463-76.
[http://dx.doi.org/10.1265/jjh.28.463] [PMID: 4800146]
[45]
Adler-Hradecky C, Kelentey B. On the toxicity and local analgesic activity of p-hydroxybenzoic acid esters. Arch Int Pharmacodyn Ther 1960; 128: 135-42.
[PMID: 13681509]
[46]
Sokol H. Recent developments in the preservation of pharmaceuticals. Drug Stand 1952; 20: 89-106.
[47]
Schuebel K. The toxicology of the new food preservatives p-chlorobenzoic add and esters of p-oxyben-zoic acid. Munch Med Wochenschr 1930; 77: 13-4.
[48]
Johnson W, Bergfeld WF, Belsito DV, et al. Safety assessment of benzyl alcohol, benzoic acid and its salts, and benzyl benzoate. Int J Toxicol 2017; 36(S3): 5S-30S.
[http://dx.doi.org/10.1177/1091581817728996] [PMID: 29243541]
[49]
Bax NMA, van der Zee DC, Turner NM, Rademaker CMA, Gemke RJBJ. Cetrimide overdose. Surg Endosc 1997; 11(9): 967-8.
[http://dx.doi.org/10.1007/s004649900501] [PMID: 9294287]
[50]
Helgeland K, Heyden G, Rölla G. Effect of chlorhexidine on animal cells in vitro. Eur J Oral Sci 1971; 79(2): 209-15.
[http://dx.doi.org/10.1111/j.1600-0722.1971.tb02011.x]
[51]
Yost LJ, Rodricks JD, Turnbull D, et al. Human health risk assessment of chloroxylenol in liquid hand soap and dishwashing soap used by consumers and health-care professionals. Regul Toxicol Pharmacol 2016; 80: 116-24.
[http://dx.doi.org/10.1016/j.yrtph.2016.06.003] [PMID: 27316554]
[52]
Bruch MK. Chloroxylenol: An old-new antimicrobial. In: Hanbook Disinfect Antiseptics. Marcel Dekker, Inc., New York, NY 1996; pp. 265-94.
[53]
Nakamura H, Yokoyama Y, Motoyoshi S, et al. The pharmacological profile of 2-(8-methyl-10,11-dihydro-11-oxodibenz[b,f]oxepin-2-yl)propionic acid (AD-1590), a new non-steroidal anti-inflammatory agent with potent antipyretic activity. Arzneimittelforschung 1983; 33(11): 1555-69.
[PMID: 6607053]
[54]
Clements CJ. The evidence for the safety of thiomersal in newborn and infant vaccines. Vaccine 2004; 22(15-16): 1854-61.
[http://dx.doi.org/10.1016/j.vaccine.2003.11.017] [PMID: 15121295]
[55]
Smith MI. The pharmacological action of certain phenol esters, with special reference to the etiology of so-called ginger paralysis (second report). Public Heal Reports 1930; 2509-24.
[56]
Shen X, Sun X, Xie Q, et al. Antimicrobial effect of blueberry (Vaccinium corymbosum L.) extracts against the growth of Listeria monocytogenes and Salmonella enteritidis. Food Control 2014; 35(1): 159-65.
[http://dx.doi.org/10.1016/j.foodcont.2013.06.040]
[57]
Bower CK, Schilke KF, Daeschel MA. Antimicrobial properties of raisins in beef jerky preservation. J Food Sci 2003; 68(4): 1484-9.
[http://dx.doi.org/10.1111/j.1365-2621.2003.tb09671.x]
[58]
Abouzeed YM, Zgheel F, Elfahem AA, et al. Identification of phenolic compounds, antibacterial and antioxidant activities of raisin extracts. Open Vet J 2019; 8(4): 479-84.
[http://dx.doi.org/10.4314/ovj.v8i4.20] [PMID: 30775288]
[59]
Benkeblia N. Antimicrobial activity of essential oil extracts of various onions (Allium cepa) and garlic (Allium sativum). Lebensm Wiss Technol 2004; 37(2): 263-8.
[http://dx.doi.org/10.1016/j.lwt.2003.09.001]
[60]
Turgis M, Han J, Caillet S, Lacroix M. Antimicrobial activity of mustard essential oil against Escherichia coli O157:H7 and Salmonella typhi. Food Control 2009; 20(12): 1073-9.
[http://dx.doi.org/10.1016/j.foodcont.2009.02.001]
[61]
Şengün Yİ, Yücel E. Antimicrobial properties of wild fruits. Biolog Divers Conserv 2015; 8(1): 69-77.
[62]
Gaafar AA, Salama ZA, Askar MS, El-Hariri DM, Bakry BA. In vitro antioxidant and antimicrobial activities of Lignan flax seed extract (Linumusitatissimum, L.). Int J Pharm Sci Rev Res 2013; 23(2): 291-7.
[63]
Erdem ME, Koral S, Kay??? , Çebi H, Keskin? . Investigation of the Sources of Transmission of Total Mesophyll Bacteria and Some Pathogenic Microorganisms in Anchovy Fish (Engraulis encrasicholus) Caught in Trabzon Province.2010. Vet Hekim Der Derg 2013; 84(1): 26-35.
[64]
Connolly P, Bloomfield SF, Denyer SP. A study of the use of rapid methods for preservative efficacy testing of pharmaceuticals and cosmetics. J Appl Bacteriol 1993; 75(5): 456-62.
[http://dx.doi.org/10.1111/j.1365-2672.1993.tb02802.x] [PMID: 8300446]
[65]
Peter G, Marge R. An Update On Parabens. Dermatologist 2008; 30(5): 1-5.
[66]
Vandenberg LN, Bugos J. Assessing the public health implications of the food preservative propylparaben: Has this chemical been safely used for decades. Curr Environ Heal reports 2021; 8(1): 1-17.
[http://dx.doi.org/10.1007/s40572-020-00300-6]
[67]
Barr L, Metaxas G, Harbach CAJ, Savoy LA, Darbre PD. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum. J Appl Toxicol 2012; 32(3): 219-32.
[http://dx.doi.org/10.1002/jat.1786] [PMID: 22237600]
[68]
Nasa P. Safety margin of cosmetics: A review. World J Pharm Res 2014; 3(5): 1024-34.
[69]
Warbanski M. The ugly side of the beauty industry. Herizons Mag 2007; 21(1): 24-8.
[70]
Sasseville D. Hypersensitivity to preservatives. Dermatol Ther 2004; 17(3): 251-63.
[http://dx.doi.org/10.1111/j.1396-0296.2004.04028.x] [PMID: 15186371]
[71]
Cornell EM, Janetos TM, Xu S. Time for a makeover‐cosmetics regulation in the United States. J Cosmet Dermatol 2019; 18(6): 2041-7.
[http://dx.doi.org/10.1111/jocd.12886] [PMID: 30950176]
[72]
Nair B, Elmore AR. Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite. Int J Toxicol 2003; 22(S2): 63-88.
[http://dx.doi.org/10.1080/10915810305077X] [PMID: 14555420]
[73]
Marceaux JC, Dilks LS, Hixson S. Neuropsychological effects of formaldehyde use. J Psychoactive Drugs 2008; 40(2): 207-10.
[http://dx.doi.org/10.1080/02791072.2008.10400632] [PMID: 18720671]
[74]
Zachariae C, Hall B, Cottin M, Cupferman S, Andersen KE, Menné T. Experimental elicitation of contact allergy from a diazolidinyl urea-preserved cream in relation to anatomical region, exposure time and concentration. Contact Dermat 2005; 53(5): 268-77.
[http://dx.doi.org/10.1111/j.0105-1873.2005.00712.x] [PMID: 16283905]
[75]
Doi T, Takeda A, Asada A, Kajimura K. Characterization of the decomposition of compounds derived from imidazolidinyl urea in cosmetics and patch test materials. Contact Dermat 2012; 67(5): 284-92.
[http://dx.doi.org/10.1111/j.1600-0536.2012.02073.x] [PMID: 22564140]
[76]
Aakhus AE, Warshaw EM. Allergic contact dermatitis from cetyl alcohol. Dermatitis 2011; 22(1): 56-7.
[http://dx.doi.org/10.2310/6620.2011.10086] [PMID: 21291645]
[77]
Moser CL, Meyer BK. Comparison of compendial antimicrobial effectiveness tests: A review. AAPS Pharm Sci Tech 2011; 12(1): 222-6.
[http://dx.doi.org/10.1208/s12249-010-9575-9] [PMID: 21221871]
[78]
Monographs NPG. United States pharmacopeia and national formulary USP 41–NF 36. In: Rockville, MD: The United States Pharmacopeial Convention, Inc. 2018.
[79]
Leon S, Isadore K. Drugs and the pharmaceutical sciences. Eds, Generic Drug Product Development Solid Oral Dosage Forms. (In: 2nd eds..). CRC Press: Florida. 2013; 397.
[80]
Marles RJ, Barrett ML, Barnes J, et al. United States pharmacopeia safety evaluation of spirulina. Crit Rev Food Sci Nutr 2011; 51(7): 593-604.
[http://dx.doi.org/10.1080/10408391003721719] [PMID: 21793723]

Rights & Permissions Print Cite
Article Metrics
35
2
© 2024 Bentham Science Publishers | Privacy Policy