Updates in Ocular Antifungal Pharmacotherapy: Formulation and Clinical Perspectives

Thakkar, Ruchi; Patil, Abhay; Mehraj, Tabish; Dudhipala, Narendar; Majumdar, Soumyajit

doi:10.1007/s12281-019-00338-6

Cited by 12 publications

(11 citation statements)

References 106 publications

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“…Notwithstanding the fact that natamycin is used as the first-line treatment for fungal keratitis, other antifungals such as voriconazole, ketoconazole, and fluconazole, etc. can also be used [ 48 ]. Voriconazole possesses low solubility in the gastric fluid, which may affect the bioavailability as well as the therapeutic outcome.…”

Section: Smart Ocular Delivery Using Stimuli-responsive In Situ Gel Platformmentioning

confidence: 99%

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research

et al. 2021

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Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution–gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.

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Section: Smart Ocular Delivery Using Stimuli-responsive In Situ Gel Platformmentioning

confidence: 99%

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research

et al. 2021

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“…Only 1–5% of the active moiety applied to the ocular surface reaches the deeper intraocular tissues while the remaining amount overflows from the conjunctival sac and/or is lost through the conjunctiva and nasolacrimal drainage and could produce systemic side effects [ 15 , 16 ]. Various techniques to improve ocular bioavailability of drugs such as the addition of mucoadhesive agents [ 17 ] and viscosity enhancers in liquid dosage forms, prodrugs [ 18 , 19 ], ion-exchange resin-based formulations [ 20 ], films [ 21 ], emulsions [ 22 ], implants [ 23 ], in-situ gelling systems [ 24 , 25 ], and controlled systems, such as ocular inserts [ 26 ], have been explored in an effort to overcome the many drawbacks associated with conventional ocular drug delivery systems. These strategies aim to improve retention at the ocular surface or increase transcorneal penetration, or both.…”

Section: Introductionmentioning

confidence: 99%

Design of Topical Ocular Ciprofloxacin Nanoemulsion for the Management of Bacterial Keratitis

et al. 2021

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Bacterial keratitis (BK) is a critical ocular infection that can lead to serious visual disability. Ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LFX) have been accepted as monotherapies by the US Food and Drug Administration for BK treatment. CIP is available commercially at 0.3% w/v concentration as an ophthalmic solution and as an ointment for ocular delivery. Because of solubility issues at physiological pH, CIP precipitation can occur at the corneal surface post instillation of the solution dosage form. Consequently, the ocular bioavailability of CIP is reduced. The ointment dosage form is associated with side effects such as blurred vision, itching, redness, eye discomfort, and eye dryness. This study aimed to design a CIP loaded nanoemulsion (NE; CIP-NE) to facilitate drug penetration into the corneal layers for improved therapeutic outcomes as well as to overcome the drawbacks of the current commercial ophthalmic formulations. CIP-NE formulations were prepared by hot homogenization and ultrasonication, using oleic acid (CIP-O-NE) and Labrafac® Lipophile WL 1349 (CIP-L-NE) as the oily phase, and Tween® 80 and Poloxamer 188 as surfactants. Optimized CIP-NE was further evaluated with respect to in vitro release, ex vivo transcorneal permeation, and moist heat sterilization process, using commercial CIP ophthalmic solution as a control. Optimized CIP-O-NE formulation showed a globule size, polydispersity index, and zeta potential of 121.6 ± 1.5 nm, 0.13 ± 0.01, and −35.1 ± 2.1 mV, respectively, with 100.1 ± 2.0 % drug content and was spherical in shape. In vitro release and ex vivo transcorneal permeation studies exhibited sustained release and a 2.1-fold permeation enhancement, respectively, compared with commercial CIP ophthalmic solution. Autoclaved CIP-O-NE formulation was found to be stable for one month (last time-point tested) at refrigerated and room temperature. Therefore, CIP-NE formulation could serve as an effective delivery system for CIP and could improve treatment outcomes in BK.

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“…Different formulation approaches have been developed to minimize KET side effects, enhance drug therapeutic activity, and sustain drug delivery. KET-loaded nanostructured lipid carriers, nano-sponges, poly(lactide-co-glycolide) nanoparticles, and lipid-polyethylene glycol-based nanoparticles have recently been reported to achieve these goals [ 7 , 8 , 9 , 10 ]. Utilization of these approaches is required for the effective treatment of fungal keratitis.…”

Section: Introductionmentioning

confidence: 99%

Study the Antifungal and Ocular Permeation of Ketoconazole from Ophthalmic Formulations Containing Trans-Ethosomes Nanoparticles

et al. 2021

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Ketoconazole (KET), a synthetic imidazole broad-spectrum antifungal agent, is characterized by its poor aqueous solubility and high molecular weight, which might hamper its corneal permeation. The aim was to develop an ophthalmic formulation loaded with optimized trans-ethosomal vesicles to enhance KET ocular permeation, antifungal activity, rapid drug drainage, and short elimination half-life. Four formulation factors affecting the vesicles’ size, zeta potential, entrapment efficiency, and flexibility of the trans-ethosomes formulations were optimized. The optimum formulation was characterized, and their morphological and antifungal activity were studied. Different ophthalmic formulations loaded with the optimized vesicles were prepared and characterized. The ocular irritation and in vivo corneal permeation were investigated. Results revealed that the drug-to-phospholipid-molar ratio, the percentage of edge activator, the percentage of ethanol, and the percentage of stearyl amine significantly affect the characteristics of the vesicles. The optimized vesicles were spherical and showed an average size of 151.34 ± 8.73 nm, a zeta potential value of +34.82 ± 2.64 mV, an entrapment efficiency of 94.97 ± 5.41%, and flexibility of 95.44 ± 4.33%. The antifungal activity of KET was significantly improved following treatment with the optimized vesicles. The developed in situ gel formulations were found to be nonirritating to the cornea. The trans-ethosomes vesicles were able to penetrate deeper into the posterior eye segment without any toxic effects. Accordingly, the in situ developed gel formulation loaded with KET trans-ethosomes vesicles represents a promising ocular delivery system for the treatment of deep fungal eye infections.

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Updates in Ocular Antifungal Pharmacotherapy: Formulation and Clinical Perspectives

Cited by 12 publications

References 106 publications

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research

Design of Topical Ocular Ciprofloxacin Nanoemulsion for the Management of Bacterial Keratitis

Study the Antifungal and Ocular Permeation of Ketoconazole from Ophthalmic Formulations Containing Trans-Ethosomes Nanoparticles

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