title: Characterisation and in vitro stability of low-dose, lidocaine-loaded poly(vinyl alcohol)-tetrahydroxyborate hydrogels.
abstract: Poly(vinyl alcohol) hydrogels cross-linked with the tetrahydroxyborate anion possess textural and rheological properties that can be used as novel drug-loaded vehicles for application to traumatic wounds. However, addition of soluble drug substances causes concentration-dependent phase separation and rheological changes. The aim of this work was to investigate the effect of adding a local anaesthetic, but keeping the concentration low in an attempt to prevent these changes. Cross-linked hydrogels prepared from three grades of poly(vinyl alcohol) were characterised rheologically. Temperature sweep studies showed an elevated complex viscosity upon moving from 25°C to 80°C, which remained high for 48 h following completion of the cycle. Adhesion to model dermal surfaces achieved a maximum of 2.62 N cm(-2) and were greater than that observed to epidermal substrates, with a strong dependence on the rate of detachment used during testing. An optimised formulation (6% w/w PVA (31-50; 99) and 2% w/w THB) containing lidocaine hydrochloride loaded to an upper maximum concentration of 1.5% w/w was assessed for phase separation and drug crystallisation. After six months, crystallisation was present in formulations containing 0.7% and 1.5% lidocaine HCl. Changes in pH in response to increases in lidocaine loading were low. Drug release was shown to operate via a non-Fickian process for all three concentrations, with 60% occurring after approximately 24h. It can be concluded that using a low concentration of lidocaine hydrochloride in hydrogels based on poly(vinyl alcohol) will result in crystallisation. Furthermore, these hydrogels are unlikely to induce rapid anaesthesia due to the low loading and slow release kinetics.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes, Ulster University, Cromore Road, Coleraine, Co. Londonderry BT52 1SA, UK; Faculty of Pharmacy, Pharmaceutical Technology Department, University of Tanta, Tanta 31111, Egypt.
authors.forename: D H
authors.initials: DH
authors.lastname: Abdelkader
authors.affiliation: Faculty of Pharmacy, Pharmaceutical Technology Department, University of Tanta, Tanta 31111, Egypt.
authors.forename: M A
authors.initials: MA
authors.lastname: Osman
authors.affiliation: Faculty of Pharmacy, Pharmaceutical Technology Department, University of Tanta, Tanta 31111, Egypt.
authors.forename: S A
authors.initials: SA
authors.lastname: El-Gizawy
authors.affiliation: Sunderland Pharmacy School, University of Sunderland, Sunderland SR1 3SD, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Faheem
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes, Ulster University, Cromore Road, Coleraine, Co. Londonderry BT52 1SA, UK. Electronic address: p.mccarron@ulster.ac.uk.
authors.forename: P A
authors.initials: PA
authors.lastname: McCarron
mesh_terms: D000268:Adhesiveness; D000779:Anesthetics, Local / Q000737:chemistry*; D000818:Animals; D001881:Borates / Q000737:chemistry*; D003460:Crystallization; D065546:Drug Liberation; D004355:Drug Stability; D020100:Hydrogels / Q000737:chemistry*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D012212:Rheology; D012867:Skin / Q000737:chemistry; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D001881:Borates; D020100:Hydrogels; D011142:Polyvinyl Alcohol; D008012:Lidocaine
keywords: Lidocaine hydrochloride; PVA–THB hydrogels; Texture analysis; Topical delivery; Viscoelasticity