Int J Pharm. 2019 Jul 20;566:111-125. doi: 10.1016/j.ijpharm.2019.05.059. Epub 2019 May 23.

Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma.

International journal of pharmaceutics

Mohammad Tighsazzadeh, John C Mitchell, Joshua S Boateng

PMID: 31129346 DOI: 10.1016/j.ijpharm.2019.05.059

Abstract

Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.

Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.

Keywords: Composite films; Glaucoma; HPMC; Hyaluronic acid; Mucoadhesion ocular delivery; Timolol

Substances

• Adrenergic beta-Antagonists
• Hypromellose Derivatives
• Timolol
• Hyaluronic Acid

MeSH terms

• Administration, Ophthalmic
• Adrenergic beta-Antagonists / administration & dosage*
• Adrenergic beta-Antagonists / chemistry
• Cell Survival / drug effects
• Drug Delivery Systems*
• Drug Liberation
• Glaucoma / drug therapy
• HeLa Cells
• Humans
• Hyaluronic Acid / administration & dosage*
• Hyaluronic Acid / chemistry
• Hypromellose Derivatives / administration & dosage*
• Hypromellose Derivatives / chemistry
• Timolol / administration & dosage*
• Timolol / chemistry

Publication Types

• Journal Article