A&C produces two high purity GMP grades of Polyethylene Glycol 400 (PEG 400) excipient that far exceed the most stringent quality, safety, purity and suitability requirements for pharmaceutical use.
What is PEG 400?
PEG 400 is a clean, simple, somewhat viscous, colourless and odourless liquid polyethylene glycol. Many PEGs are possible with varying chain lengths from tens to hundreds or even thousands of repeating ethylene oxide links in their chains. PEG 400 is one of the shorter polymers having a nominal average molecular weight, Mn, of 400, which corresponds to a chain length of about 8-9 links. It is highly valued in pharmaceutical applications due to its low toxicity and its exceptional ability to solubilise polar APIs (Active Pharmaceutical Ingredients). PEG 400 is generally considered stable, non-reactive, soluble in all proportions with water and also soluble in acetone, alcohols, benzene, glycerine, glycols and aromatic hydrocarbons. This versatile excipient has found application in topical, ophthalmic, oral and parenteral dosage forms. It is recognised worldwide as an effective solvent or API ‘vehicle’ and has monographs in the major national Pharmacopoeias.
Is there a problem with commercial grade PEG 400?
While generally considered stable all PEGs are somewhat susceptible to oxidative degradation(1). Many studies have shown that these excipients will degrade through oxidative pathways forming peroxides when exposed to air. Peroxides, when present, can be catalytic in PEG degradation ultimately causing loss of viscosity and increasing acidity over time. These degradation pathways also exist in the absence of oxygen if the peroxide and other impurities pre-exist in the excipient prior to drug formulation. PEG degradation and impurities can adversely affect the drug stability(2). Presence of peroxide, aldehyde, residual reactants, moisture and trace acids can all lead to adverse effects. Most pharmaceutical grade PEGs 400 easily meet monograph specifications but can still contain sufficient trace impurities that drug formulations may experience early drug product degradation in dosage forms where PEG 400 is used.
What do the regulators require?
The EU and North American regulators require PEG 400 to be manufactured with excipient GMP controls that meet the regional Pharmacopoeial requirements of the governing monograph specifications only. As such, allowable levels of trace impurities can still have a negative impact on PEG 400 both for the excipient raw material and drug products that are formulated with it. For highly sensitive APIs in drug formulations a very Refined PEG 400 is worth consideration as it can lead to enhanced drug stability.
A&C manufactures two high purity GMP grades of PEG 400
A&C produces two grades of PEG 400. The first meets all requirements for GMP and USP-NF specifications. The second is further purified through a proprietary process that exhaustively removes trace impurities without affecting the nature or purity of the PEG 400 itself. This Refined PEG 400 has demonstrably enhanced stability which is further protected by a specially selected container closure system with nitrogen overlay to maintain the ingredient until it is ready for use.
• Polyethylene Glycol 400 NF
o An excipient grade GMP manufactured ingredient complying to IPEC GMP standard
o Meets USP-NF requirements
o Truly GMP and GDP compliant start to finish, full supply chain transparency
• Polyethylene Glycol 400 Refined Multi-Compendial Low Endotoxin
o A highly refined grade ingredient that meets the IPEC GMP standard
o Meets USP-NF and Ph. Eur. Compendia
o Trace impurities are exhaustively removed to levels far below requirements leading to enhanced product stability
o BET testing (additional specification)
A&C prides itself on strict controls, holds ISO 9001:2015 and EXCiPACT quality certifications, has a Drug Establishment license from Health Canada for manufacturing APIs and is audited by Health Canada and the US FDA.
If you use PEG 400 for pharmaceutical applications with sensitive APIs then we believe you should strongly consider our Refined product because of its low impurities and enhanced stability.
(1) Bergh M. et al., Formation of formaldehyde and peroxides by air oxidation of high purity polyethylene surfactants, Contact Derm 39(1), 14, 1998
(2) Taneja V. et al., Purity of PEG 400 affects API stability, Amer Assoc Pharm Sci Annual Meeting 2006