Analysis of residual crosslinking agent content in UV cross-linked poly(ethylene oxide) hydrogels for dermatological application by gas chromatography

Abstract

Acrylates have been widely used in the synthesis of pharmaceutical polymers. The quantitation of residual acrylate monomers is vital as they are strong irritants and allergens, but after polymerization, are relatively inert, causing no irritation and allergies. Poly(ethylene oxide) (PEO) hydrogels were prepared using pentaerythritol tetra-acrylate (PETRA) as UV crosslinking agent. A simple, accurate, and robust quantitation method was developed based on gas chromatographic techniques (GC), which is suitable for routine analysis of residual PETRA monomers in these hydrogels. Unreacted PETRA was initially identified using gas chromatography–mass spectrometry (GC–MS). The quantitation of analyte was performed and validated using gas chromatography equipped with a flame ionization detector (GC–FID). A linear relationship was obtained over the range of 0.0002%–0.0450% (m/m) with a correlation coefficient (r2) greater than 0.99. The recovery (>90%), intra-day precision (%RSD <0.67), inter-day precision (%RSD <2.5%), and robustness (%RSD <1.62%) of the method were within the acceptable values. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.0001% (m/m) and 0.0002% (m/m), respectively. This assay provides a simple and quick way of screening for residual acrylate monomer in hydrogels.

Effect of Drug Loading Method and Drug Physicochemical Properties on the Material and Drug Release Properties of Poly (Ethylene Oxide) Hydrogels for Transdermal Delivery

“…PETRA was then added into the premixed gel, and the entire mixtures were further stirred for 8 h until homogeneous. The cross-linker concentration was fixed at 5% w / w , as this concentration was found to be optimum in producing gel films with good mechanical properties [ 4 ], as well as being safe for dermatological application [ 6 ]. The viscous mixture was allowed to stand for 16 h to remove entrapped air bubbles before it was cast onto a glass tile (dimension = 30 cm × 30 cm).…”

“…The principal concern of this cross-linking method is the presence of residual acrylate monomer. However, the inclusion of pentaerythritol tetraacrylate (PETRA) as cross-linking agent was evaluated to be safe for dermatological application as long as it is within the maximum acceptable limit of 10% w / w [ 6 ].…”

Novel Injectable Hydrogel Formulations and Gas Chromatography Analysis of the Residual Crosslinker in Formulations Intended for Pharmaceutical and Cosmetic Applications

“…In previous studies, PT has been used as a crosslinker of polyethylene oxide (PEO) hydrogel films synthesised using UV radiation [29]. Other studies suggest that when PT absorbs energy from UV photons, its acrylate group generates reactive-free radicals, which initiates the crosslinking of repeated units of the polymer with PT radicals via recombination [29]. However, it is difficult to induce the free radicals on PT without adding a photoinitiator.…”

Studies on Novel Methods for Formulating Novel Cross-Linked Hydrogel Films of Hyaluronic Acid

“…Therefore, it is important to conduct residual content analysis for PT in the optimised hydrogel films and, subsequently, to adjust the PT amount in the formulation if necessary, so as to ensure that there is no unreacted PT and to establish the biocompatibility of our novel hydrogel films. We will conduct this analysis using the method we previously developed for the quantification of residual PT in PEO hydrogel films [17]. Toxicological studies of PT and similar crosslinking agents on guinea pigs showed that PT had a lower sensitising effect [18].…”