Ocular Inserts – A Potential Ocular Controlled Drug Delivery Systems

Ocular drug delivery is one of the most challenging delivery tasks faced by Pharmaceutical researchers. Major barriers in ocular medication are the ability to maintain a therapeutic level of the drug at the site of action for a sustained duration. The ophthalmic preparations are available as sterile, buffered, isotonic solution. Various types of dosage forms are applied as the delivery system for the ocular delivery of drugs. The most prescribed dosage form is the eye drop solution as drops are easier to administer. Suspensions, gelled systems, ointment are also used for prolonged therapeutic action. Evaluation of ophthalmic preparations should be non-irritating to the ocular tissue. Homogenous i.e., particles uniformly dispersed, smooth, free from lumps and agglomerates. It should not cause blurred vision. Also it should not cause intolerable foreign body sensation. The formulation will be Sterile and adequately preserved or physically and chemically stable. New ocular drug delivery systems: Using eye drops to administer drugs needs frequent application. Prolonged drug release can be achieved using ophthalmic inserts, solid devices placed in the eye, but the inserts must then be removed when they are no longer needed. Different new drug delivery systems which are designed in such a way that they release the drug at predetermined and predictable rates thus eliminating the frequent administration of the drug for example ocular insert. The systems generally include controlled, delayed and or sustained release bioerodible implantable elements having multiple layers of different materials and/or different concentrations of materials. The elements generally include an inner layer, or core, including a therapeutic agent, and one or more outer layers made of polymeric materials, for example substantially pure polymeric materials. In the area of topical ocular administration, important efforts concern the design and the conception of new ophthalmic drug delivery systems able to prolong the residence time. The purpose of this review is to provide an update on the current knowledge within this field of ocular drug delivery.

The Second Annual Ophthalmic Drug Development and Delivery Summit was held on 19 – 20 September 2006 in San Diego, CA, US. The 2-day symposium, having a highly focused theme, was packed with cutting-edge science, insightful overviews and networking opportunities. With a total of 11 recognized specialists presenting reviews and recent results in the advancement of ocular drug development and delivery, the invited expert speaking faculty presented the latest preclinical and clinical developments in novel ophthalmic therapies and drug delivery technology. The talks included various case studies from primary investigators and pharmaceutical companies touching upon key topics: updates on current clinical trials, study design issues, sustained delivery to the eye, views of the vitreous space as a drug reservoir, new developments in dry and wet age-related macular degeneration and diabetic retinopathy, formulation for optimal drug delivery, differences and similarities in developing drugs for the eye compared with other targets, pharmacokinetics, novel ocular delivery methods and devices, delivery of proteins and peptides, focal drug delivery, non-invasive drug delivery to the eye, neuroprotection challenges, in vitro and in vivo models for glaucoma and angiogenesis for early efficacy estimation, and toxicology. Overall, the 2-day annual symposium continues to grow as an efficient platform for fostering discussion on a range of scientific topics and challenges and avenues for building collaborative partnerships in ophthalmic drug development.

Precise Fabrication of Ocular Inserts Using an Innovative Laser-Driven CaliCut Technology: In Vitro and in Vivo Evaluation

Ocular route of drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. The anatomy, physiology and biochemistry of the eye render this organ exquisitely impervious to foreign substances. The challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage In spite of extensive pharmacological and clinical data pointing to the usefulness and advantages of solid devices for topical drug delivery to the eye, liquid, and to a smaller extent, gel-type preparations appear to enjoy the continued interest of manufacturers and ophthalmologists. The main purpose of preparing ocular insert is to increase ocular bioavailability of drug. Ocular inserts maintain the drug concentration within a desired range. Fewer administrations are required so they increase patient compliance. In the present update, the advantages, disadvantages and requirement for success of ocular inserts, and examine the few inserts which are available on the market or are being developed by pharmaceutical companies for drug delivery. In this review, we have focused on the present era of ocuserts helps in treating eye diseases. Â

Therapeutic nanoemulsions in ophthalmic drug administration: Concept in formulations and characterization techniques for ocular drug delivery

Ocular drug delivery poses significant challenges in maintaining therapeutic drug levels at the targeted site for an extended period. Traditional ocular medications, such as eye drops, often necessitate frequent administration and may lead to issues like corneal crystalline deposits. In response to these challenges, novel formulations like ocular inserts have emerged. Ocular inserts are specialized drug delivery systems designed for ophthalmic application, offering controlled release, and prolonged drug activity. This review explores the benefits of ocular inserts over conventional dosage forms, highlighting their ability to enhance ocular residence time and bioavailability through slow, constant drug release. Additionally, the review covers the physiology of the eye and various preparation and evaluation methods of ocular inserts, providing insights into their potential as effective alternatives in ocular drug delivery.

Controlled release of drugs to the eye tissues is still an important, though challenging topic of research in the area of pharmaceutical technology. The eye is an organ highly protected from extraneous compounds by anatomical, functional and biochemical mechanisms. Such defences often limit the time of contact of the formulation with the eye surface and lead to an insufficient bioavailability of the applied drugs, especially at the level of eye posterior segment. Many nanotechnology strategies have been exploited for the diagnosis and cure of ocular diseases. They range from medical application of nanomaterials, including controlled drug and gene delivery systems, to nanoelectronic biosensors, to nanodevices for in vivo imaging and diagnosis, to implantable biomaterials for tissue regeneration and prolonged targeted therapy. Nanosized ocular drug delivery systems have shown important results in ocular drug delivery in the last years, both as topical applications on the eye surface or after intraocular administration. These colloidal carriers can be suitably engineered to overcome corneal and retinal barriers to drug penetration, protect the encapsulated drug, and prolong its activity by a controlled and/or prolonged site-specific release profile. Although the basic research on ophthalmic delivery systems supplies many technological approaches, very few of them have been able to reach a clinical relevance or to be translated into pre-industrial or industrial applications. The main reason lies in the complexity and specificity of the formulation parameters that ophthalmic products always require to tackle the high sensitivity of ocular tissues. This review surveys some of the more recent patents regarding nanotechnology applications to ophthalmic controlled and targeted drug delivery. Keywords: Nanotechnology, Ophthalmic Drug Delivery, Controlled drug delivery, dendrimers, intraocular release, intravitreal delivery, iontophoresis, liposomes, microparticles, nanocarriers, nanoemulsions, nano-eye drops, nanoparticles, ocular therapy, SLN

Purpose: The poor bioavailability of drugs in the ocular delivery systems is an important issue and development of delivery systems with prolonged release profile could be in a major importance. This study aims to develop an ocular delivery system using electrospun nanofibers to be a candidate insert for delivery of triamcinolone acetonide.Methods: For this purpose, three different chitosan-based formulations were prepared by electrospinning method, and electrospun nanofibers were compared to a formulation comprising hydrophobic polymers (Eudragit S100 and Zein). The electrospun nanofibers were characterized by SEM and FTIR analyses. The release profile and release kinetic models of all the formulations were also examined.Results: The SEM photographs of electrospun nanofibers revealed that among the four designed formulations, formulation obtained by electrospinning of chitosan and PVP possessed the best quality and the minimum size (120 ±30 nm) , which resulted the most uniform and bead-free nanofibers. This formulation also possessed the prolonged release profile of triamcinolone acetonide and was the only electrospun nanofiber following the zero-order kinetic profile. Due to the small diameter and uniformity of this formulation, the prolonged and well controlled release profile, it could be taken into account as a candidate to overcome the drawbacks of the commonly used ocular delivery systems and be used as ocular insert.Conclusion: This study confirmed the ability of electrospun nanofibers to be used as ocular inserts for delivery of ophthalmic drugs.

The eye is God's most wonderful creation of all the sense organs in the human body since it allows us to see numerous objects both near and far away. An ocular implant is a cutting-edge device for treating eye diseases. The design and development of an ocular insert has always been a difficulty for pharmaceutical researchers and manufacturers. Ocuserts, also known as ophthalmic inserts, are "sterile preparations in the form of solid or semisolid, whose size and shape are specially designed to be applied to the eyes". Solvent casting, the Glass Substrate technique, and hot melt extrusion were used to create ocuserts. The inserts can be classed as insoluble, soluble, or biodegradable based on their solubility. The drug's release from the insert is determined by its diffusion, osmosis, and bioerosion. The ocuserts' objective is to enhance pharmaceutical contact with conjunctiva tissue, resulting in constant dose release. Uniform ocular drug levels reduce systemic side effects, minimise doses, and improve patient compliance. Preparing ocular inserts aims to enhance medication bioavailability. Ocular inserts keep medication concentrations within the appropriate range. Using fewer administrations leads to better patient compliance. The page covers the eye's many parts and anatomy, along with an explanatory image.This study aims to offer an update on current understanding in ocular medication delivery. Also, this review focuses on the current usage of ocuserts to treat eye disorders.

Ocular diseases may be treated via different routes of administration, such as topical, intracameral, intravitreal, oral and parenteral. Among them the topical route is most accepted by patients, although it provides in many cases the lowest bioavailability. Indeed, when a topical formulation reaches the precorneal area, i.e., the drug absorption and/or action site, it is rapidly eliminated due to eye protection mechanisms such as blinking, basal and reflex tearing, and naso-lacrimal draining. To avoid this and to reduce the frequency of dosing, various strategies have been developed to prolong drug residence time after topical administration. These strategies include the use of viscosity increasing and mucoadhesive excipients as well as combinations thereof. From the drug delivery system point of view, liquid and semisolid formulations are preferred over solid formulations such as ocular inserts and contact lenses. Furthermore, liquid and semisolid formulations can contain nano- and microcarrier systems that contribute to a prolonged residence time. Within this review an overview about the different types of excipients and formulations as well as their performance in valid animal models and clinical trials is provided.

Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed.

Topical ocular drug delivery systems: Innovations for an unmet need

Journal of Ocular Pharmacology and TherapeuticsVol. 29, No. 2 Featured ColumnEyes on New Product Development: Ophthalmic Drug DeliveryGary D. NovackGary D. NovackSearch for more papers by this authorPublished Online:13 Mar 2013https://doi.org/10.1089/jop.2013.1503AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Eyes on New Product Development: Ophthalmic Drug Delivery." , 29(2), pp. 90–91FiguresReferencesRelatedDetailsCited byMicelles: Promising Ocular Drug Carriers for Anterior and Posterior Segment Diseases Meltem Ezgi Durgun, Sevgi Güngör, and Yıldız Özsoy24 July 2020 | Journal of Ocular Pharmacology and Therapeutics, Vol. 36, No. 6Nanomedicines in the future of pediatric therapyAdvanced Drug Delivery Reviews, Vol. 73 Volume 29Issue 2Mar 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Gary D. Novack.Eyes on New Product Development: Ophthalmic Drug Delivery.Journal of Ocular Pharmacology and Therapeutics.Mar 2013.90-91.http://doi.org/10.1089/jop.2013.1503Published in Volume: 29 Issue 2: March 13, 2013PDF download

Introduction Glaucoma is a group of progressive optic neuropathies resulting in irreversible blindness. It is associated with an elevation of intraocular pressure (>21 mm Hg) and optic nerve damage. Reduction of the intraocular pressure (IOP) through the administration of ocular hypotensive eye drops is one of the most common therapeutic strategies. Patient adherence to conventional eye drops remains a major obstacle in preventing glaucoma progression. Additional problems emerge from inadequate patient education as well as local and systemic side effects associated with adminstering ocular hypotensive drugs. Areas covered Sustained-release drug delivery systems for glaucoma treatment are classified into extraocular systems including wearable ocular surface devices or multi-use (immediate-release) eye formulations (such as aqueous solutions, gels; ocular inserts, contact lenses, periocular rings, or punctual plugs) and intraocular drug delivery systems (such as intraocular implants, and microspheres for supraciliary drug delivery). Expert opinion Sustained release platforms for the delivery of ocular hypotensive drugs (small molecules and biologics) may improve patient adherence and prevent vision loss. Such innovations will only be widely adopted when efficacy and safety has been established through large-scale trials. Sustained release drug delivery can improve glaucoma treatment adherence and reverse/prevent vision deterioration. It is expected that these approaches will improve clinical management and prognosis of glaucoma.

Next-generation polymer-based nanofiber ocular inserts: fabrication innovations, therapeutic applications, regulatory perspectives, and future directions.