Manu Chaudhary, Kuntal Ganguly


Leachables and extractables are one of the most common sources of contamination in injectables. The amount of these contaminants may increase to toxic levels in case of glyerol based parenteral dosage forms used in neurotherapeutics. Glycerol, a plasticizer, softens the core plastic material and thus the number and amount of leachables increase. Three different glycerol based marketed injectable formulations, two available in plastic [Polypropylene (PP)/Low density poly ethylene (LDPE)] and the other in glass container, were kept under stress and accelerated stability testing and subjected to various tests including gas chromatography-mass spectroscopy (GC-MS) to study the type and amount of leachables. Several new leached out toxic components were identified in case of plastic (PP and LDPE) container and none in case of glass container.

Presence of Bisphenol A at a concentration more than 12 times higher/bottle compared to the recommended maximum allowable dose level (MADL) and di butyl phthalate another highly toxic compound at a concentration 2.7 times higher/bottle than tolerable daily intake decided by National Toxicology Programme are alarming findings. In vivo animal studies confirmed the neuro and endocrine disruptive potential of these impurities as well as hepatotoxicity due to oxidative stress. Thus it is concluded that the glass container is safer option for storing glycerol based products for parenteral use and use of PP and LDPE containers must be strictly prohibited for human safety.



Glycerol, mannitol, parenteral, neurotherapeutic, leachable, endocrine disruption, hepatoxicity, neurotoxicity

Full Text:

Full text in pdf


Amendment to Section 25805 Specific Regulatory Levels: Chemicals Causing Reproductive Toxicity – BPA, 2013, Office of environmental health hazard assessment, Govt. of Canada.

Bibra toxicology advice and consulting. Toxicity profile for oleic acid (1986).Accessed on 26.09.2014. Available online from loads/toxicity-profile-for-oleic-acid-1986/

Bisphenol A – Frequently Asked Questions, Office of environmental health hazard assessment. April 2013, Govt. of Canada.

Ema M, Miyawaki E, Harazono A, Kawashima K. Developmental toxicity evaluation of phthalic acid, one of the metabolites of phthalic acid esters, in rats. ToxicolLett. 1997 ;93(2-3):109-15.

Govt. of Canada. Office of environmental health hazard assessment. Amendment to Section 25805 Specific Regulatory Levels: Chemicals Causing Reproductive Toxicity – BPA. 2013.

Govt. Of Canada.Office of environmental health hazard assessment.Bisphenol A – Frequently Asked Questions April 2013. 2013.

Hodson L, Karpe F. Is there something special about palmitoleate? CurrOpinClinNutrMetab Care.2013 ; 16(2): 225-31.

Mozaffarian D, Cao H, King I B, Lemaitre R N, Song X, Siscovick D S, and Hotamisligil G S. Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes. Am J ClinNutr. 2010; 92(6): 1350–58.

Mucignat-Caretta C Ed.Neurobiology of Chemical Communication. CRC Press, Taylor and Francis Group, Boca Raton, Florida, USA.2010; 1st edition.pp.230.

Pala V, Krogh V, Muti P, Chajes V, Riboli E, Micheli A, Saadatian M, Sieri S, Berrino F. Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study.JNatl Cancer Inst. 2001; 93(14):1088-95.

Pollak A., The story behind kosher plastics.Accessed on 14.07.2014. [1 frame] Available online from

Pubchem compound summary. 12-Bromo-1-dodecanol.Accessed on 26.09.2014. Available online from http://pubchem.ncbi.nlm.nih. gov/summary/summary.cgi?cid=137895

Transport Information Service. Cargo loss prevention information from German marine insurers.Container climate. Accessed on 16.07.2014.[1 Frame]. Available online from /containe/klima/ klima.htm

United States Food and Drug Aministration. Current FDA Perspective on Leachable Impurities in Parenteral and Ophthalmic Drug products.AAPS Workshop on Pharmaceutical Stability -Scientific and Regulatory Considerations for Global Drug Development and Commercialization, 2011, Washington, DC.

United States Consumer Product Safety Commission. Toxicity Review of Di-n-butyl phthalate. Accessed on 14.07.2014. Available online from PageFiles/ 126528/toxicityDBP.pdf

Wijdicks EFM, The practice of emergency and critical care neurology. 2013.Oxford University Press. DOI: 10.1093/med/ 9780195394023.001.0001


  • There are currently no refbacks.

Copyright © 2015 BIOPHARM JOURNAL  - ISSN 2454-1397 & Powered by Sona Nfinity