Modulation of gel formation and drug-release characteristics of lidocaine-loaded poly(vinyl alcohol)-tetraborate hydrogel systems using scavenger polyol sugars

• Published in: European journal of pharmaceutics and biopharmaceutics 2008-08, Vol.69 (3), p.1135-1146
• Main Authors: Loughlin, Ryan G., Tunney, Michael M., Donnelly, Ryan F., Murphy, Diarmaid J., Jenkins, Mark, McCarron, Paul A.
• Format: Article
• Language: English
• Subjects: Anesthetics, Local - administration & dosage; Biological and medical sciences; Borate; Borates - chemistry; Chemistry, Pharmaceutical; Delayed-Action Preparations; General pharmacology; Hardness Tests; Hydrogel; Hydrogels; Hydrogen-Ion Concentration; Lidocaine - administration & dosage; Lidocaine hydrochloride; Mannitol; Mannitol - chemistry; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(vinyl alcohol); Polymers - chemistry; Polyol; Polyvinyl Alcohol - chemistry; Temperature; Topical delivery; Viscosity
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2008.01.033

Polyol sugars, displaying a plurality of hydroxyl groups, were shown to modulate tetrahydroxyborate (borate) cross-linking in lidocaine hydrochloride containing poly(vinyl alcohol) semi-solid hydrogels. Without polyol, demixing of borate cross-linked PVA hydrogels into two distinct phases was noticeable upon lidocaine hydrochloride addition, preventing further use as a topical system. d-Mannitol incorporation was found to be particularly suitable in circumventing network constriction induced by ionic and pH effects upon adding the hydrochloride salt of lidocaine. A test formulation (4% w/v lidocaine HCl, 2% w/v d-mannitol, 10% w/v PVA and 2.5% w/v THB) was shown to constitute an effective delivery system, which was characterised by an initial burst release and a drug release mechanism dependent on temperature, changing from a diffusion-controlled system to one with the properties of a reservoir system. The novel flow properties and innocuous adhesion of PVA–tetrahydroxyborate hydrogels support their application for drug delivery to exposed epithelial surfaces, such as lacerated wounds. Furthermore, addition of a polyol, such as d-mannitol, allows incorporation of soluble salt forms of active therapeutic agents by modulation of cross-linking density.