title: Novel in situ gelling ocular films for the opioid growth factor-receptor antagonist-naltrexone hydrochloride: fabrication, mechanical properties, mucoadhesion, tolerability and stability studies.
abstract: Naltrexone hydrochloride (NTX) is an innovative drug used in ophthalmology for treatment of ocular surface diseases such as impaired corneal wound healing and severe dry eye. Poor chemical stability has been a major limitation for development of NTX in solution form. The aim of this study was to develop and characterise NTX in situ ocular films for enhanced chemical stability and improved ocular tolerability. The films were prepared from different amorphous polymers and characterised for physicochemical compatibility, moisture-sorption, surface pH, mechanical properties, sterilisability, surface morphology, mucoadhesion, in vitro release, conjunctival irritation and accelerated stability at 40°C/75% relative humidity for 3 months. Glycerin (GLY)-plasticised films exhibited significantly better mechanical properties, compared with polyethylene glycol (PEG) 400 and triethylcitrate (TEC)-plasticised formulations. Superior mucoadhesion was recorded for F7 and F9 plasticised with GLY and PEG 400, respectively. The stability of NTX was significantly enhanced more than 18-times, compared with the solution form. Combination of carboxymethylcellulose sodium (CMC) and sodium alginate (ALG) in a film formulation demonstrated minimal % moisture sorption, good mechanical properties, in vitro release, excellent chemical stability and minimal conjunctival irritation lending them as promising ocular formulations.
authors.affiliation: Drug Discovery, Delivery and Patient (DDDPC) Theme, School of Pharmacy and Chemistry, Kingston University London, Kingston upon Thames, London, UK; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Mina, Egypt. Electronic address: h.abdelkader@kingston.ac.uk.
authors.forename: Hamdy
authors.initials: H
authors.lastname: Abdelkader
authors.affiliation: Vision Cognition and Neuroscience Theme, Faculty of Science, Engineering and Computing, Kingston University London, Kingston upon Thames, London, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pierscionek
authors.affiliation: Drug Discovery, Delivery and Patient (DDDPC) Theme, School of Pharmacy and Chemistry, Kingston University London, Kingston upon Thames, London, UK; School of Pharmacy, The University of Auckland, Auckland, New Zealand.
authors.forename: Raid G
authors.initials: RG
authors.lastname: Alany
mesh_terms: D000268:Adhesiveness; D060433:Administration, Ophthalmic; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003231:Conjunctivitis / Q000188:drug therapy; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005782:Gels; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D009271:Naltrexone / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D011957:Receptors, Opioid / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013314:Stress, Mechanical; D013499:Surface Properties; D013718:Tensile Strength
chemical_list: D004337:Drug Carriers; D005782:Gels; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; D009271:Naltrexone
keywords: Corneal wound healing; In situ gel ocular films; Naltrexone hydrochloride; Plasticisers; Polymers