Spanlastics nanovesicular ocular insert as a novel ocular delivery of travoprost: optimization using Box-Behnken design and in vivo evaluation.

Currently, travoprost is a synthetic prostaglandin F2α analogue used in the treatment of glaucoma, it is delivered by eye drop solution. Due to its very low bioavailability and patient non-compliance, the objective of the current study was to enhance its bioavailability, and prolong its release Spanlastic nano-vesicles gels were designed and optimized using Box-Behnken design. The optimized spanlastic nano-vesicles gel exhibited the lowest particle size (PS), polydispersity index (PDI) and the highest zeta potential (ZP), encapsulation efficiency (EE) and mucoadhesive strength was fabricated into spanlastic nano-vesicles ocular insert by solvent casting. In vivo studies showed enhanced bioavailability of travoprost spanlastic nano-vesicles gel and ocular insert compared to the marketed eye drops (travoswix®), as proven by their higher Cmax and AUC0-∞, in addition to being nonirritant to ocular surfaces. However, spanlastic nano-vesicles ocular insert showed more prolonged effect than spanlastic nano-vesicles gel. According to our study, it can be suggested that travoprost spanlastic nano-vesicles ocular insert is a novel ocular delivery system for glaucoma treatment.

Design, fabrication, and characterization of graft co-polymer assisted ocular insert: a state of art in reducing post-operative pain.

PURPOSE: Targeted delivery of drugs at appropriate concentrations to ocular tissues is required to avoid wastage. Hence, advanced systems that maximize the release of poorly soluble drugs and deliver them at ocular sites must be designed. METHODS: In this study, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol-graft copolymer) was selected as a solubilizer as well as film former for preparing ocular inserts and polyethylene glycol 400 (PEG-400) as a plasticizer. On the basis of an initial phase solubility study, the maximum concentration of Soluplus® possible was used for developing the inserts. An optimized formulation was obtained using a 32-factorial design. Two factors at three levels were used to design the ocular inserts. Soluplus® (X 1) and the plasticizer, PEG-400 (X 2), were set as the independent variables at various levels, and the Rel4h (drug release in 4 h, Y 1) and tensile strength (Y 2) were set as the dependent variables. A pre-formulation study was conducted to select suitable materials. RESULTS: Various physico-chemical parameters of the optimized formulation, including the tensile strength and folding endurance, were studied using FT-IR, DSC, XRD, and SEM. An in vitro dissolution study was conducted to determine the amount of drug released. There was no redness, swelling, or watering of the rabbit eye. CONCLUSION: It was concluded that the ocular inserts of the poorly soluble nepafenac developed using a graft-co-polymer enhanced the solubility and utilization of the drug for a prolonged period.

Nanodispersion-loaded mucoadhesive polymeric inserts for prolonged treatment of post-operative ocular inflammation.

Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded nanodispersion aiming the sustained delivery of the drug to the cornea have been developed and characterised for the treatment of post-operative ocular inflammation. Nanodispersions were prepared by ionic gelation method with various concentrations of chitosan and sodium tripolyphosphate. The developed nanodispersions were analysed for morphology, particle size, dispersion homogeneity, zeta potential, entrapment efficiency and drug release. The nanodispersion that showed the smallest particle size and the highest entrapment efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m films. The formulation with optimum physicomechanical properties was selected to study its ex vivo transcorneal permeation through freshly excised bovine cornea in comparison with the nanodispersion and the marketed eye drops (Acular®). The polymeric ocular film showed greater permeation than aqueous eye drops. Moreover, the ocular film revealed a prolonged anti-inflammatory effect compared to eye drops when applied to inflamed rabbit's eyes.

Novel in situ gelling ocular inserts for voriconazole-loaded niosomes: design, in vitro characterisation and in vivo evaluation of the ocular irritation and drug pharmacokinetics.

This work aimed to develop voriconazole in situ gelling ocular inserts loaded with niosomal suspension. Niosomes and mixed niosomes were prepared using span 40 and span 60 with pluronic L64 and pluronic F127. The entrapment efficiency percentages (EE%), mean vesicle size, polydispersity index (PI), zeta potential and in vitro drug release of these niosomes were evaluated. F3-mixed niosomes prepared with span 60 and pluronic L64 was selected, due to its highest EE; optimum vesicle size with smallest PdI and suitable release pattern of the drug (63% after 8 h). In situ ocular inserts were prepared using sodium carboxymethylcellulose (CMC Na) and sodium alginate (ALG) and characterised for surface morphology, surface pH, water uptake, mucoadhesion and in vitro release. ALG in situ ocular insert (S2) was selected for further in vivo evaluation of the ocular irritation and drug pharmacokinetics in the aqueous humour of rabbit's eyes. S2 in situ gelling ocular insert was non-irritant and showed significantly (p < 0.01) higher Cmax, delayed Tmax and increased bioavailability.

Tamarind seed polysaccharide-metformin insert: Higher ocular retention, slow-release, and efficacy against corneal burn.

Metformin (MET) can be an alternative therapeutic strategy for managing ocular burn primarily because of its pleiotropic mechanism. Longer retention on the ocular surface and sustained release are necessary to ensure the efficacy of MET for ocular application. Although the high aqueous solubility of MET is good for formulation and biocompatibility, it makes MET prone to high nasolacrimal drainage. This limits ocular residence and may be a challenge in its application. To address this, polymers approved for ophthalmic application with natural origin were analyzed through in silico methods to determine their ability to bind to mucin and interact with MET. An ocular insert of MET (3 mg/6 mm) was developed using a scalable solvent casting method without using preservatives. The relative composition of the insert was 58 ± 2.06 %w/w MET with approximately 14 %w/w tamarind seed polysaccharide (TSP), and 28 %w/w propylene glycol (PG). Its stability was demonstrated as per the ICH Q1A (R2) guidelines. Compatibility, ocular retention, drug release, and other functional parameters were evaluated. In rabbits, efficacy was demonstrated in the 'corneal alkali burn preclinical model'. TSP showed potential for mucoadhesion and interaction with MET. With adequate stability and sterility, the insert contributed to adequate retention of MET (10-12 h) in vivo and slow release (30 h) in vitro. This resulted in significant efficacy in vivo.

Development and Evaluation of Different Electrospun Cysteamine-Loaded Nanofibrous Webs: A Promising Option for Treating a Rare Lysosomal Storage Disorder.

Nanofibers can be utilized to overcome the challenges faced by conventional ophthalmic formulations. This study aimed to develop and characterize cysteamine (Cys)-loaded nanofiber-based ophthalmic inserts (OIs) as a potential candidate for the treatment of ophthalmic cystinosis using water-soluble polyvinyl alcohol (PVA)/poloxamer 407 (PO-407) and water-insoluble tetraethoxysilane (TEOS)/PVA nanofibers. Plain and Cys-loaded fibers in different proportions were prepared by the electrospinning method and studied for their morphological, physicochemical, release study, cytocompatibility effects, and stability study. The fiber formation was confirmed by scanning electron microscopy, while Fourier transform infrared spectra showed the most critical peaks for the Cys and the excipients. The release of the Cys was fast from the two polymeric matrices (≤20 min). The release from TEOS/PVA nanofibers is characterized by Case II transport (0.75 < ß < 1), while the release from PVA/PO-407 nanofibers follows Fickian diffusion (ß < 0.75). The cytocompatibility of compositions was confirmed by hen eggs tested on the chorioallantoic membrane (HET-CAM) of chick embryos. All formulations remained stable under stress conditions (40 ± 2 °C, 75 ± 5% relative humidity) regarding morphology and physicochemical characteristics. The developed nanofibrous mats could be an excellent alternative to available Cys drops, with better stability and convenience of self-administration as OIs.

Topical Advances in Mucoadhesive Ocular Drug Delivery System.

The current article mainly highlights mucoadhesive drug delivery with merits like the prolonged holding time at the action site and also provides a controlled rate of drug release for improved therapeutic outcomes. Moreover, mucosal delivery can eliminate problems of the conventional oral route, such as first pass metabolism as well as acid degradation. However, the eye has unique anatomy and physiology that can cause hindrance and challenges in comparison to the other organs of the body. Additionally, conventional delivery vehicles like solutions, suspensions, and ointments have many demerits such as rapid precorneal clearance, subject variability, drainage, and uncontrolled release from the dosage form. Therefore, novel pharmaceutical ophthalmic formulations like gels, nanosuspensions, nano-particles, liposomes, microemulsions, iontophoretic dosage forms, and ocuserts were tried and tested in the past few years for ophthalmic delivery. These novel delivery products provide enhanced solubility and bioavailability in a controlled manner to overcome conventional demerits. Here in this review, we have summarized the improvement of drug studies that are currently underway for eye drug carriers, along with stages and important aspects of novel drug delivery to the eye.

Formulation and Characterization of Electrospun Nanofibers for Melatonin Ocular Delivery.

The poor ocular bioavailability of melatonin (MEL) limits the therapeutic action the molecule could exert in the treatment of ocular diseases. To date, no study has explored the use of nanofiber-based inserts to prolong ocular surface contact time and improve MEL delivery. Here, the electrospinning technique was proposed to prepare poly (vinyl alcohol) (PVA) and poly (lactic acid) (PLA) nanofiber inserts. Both nanofibers were produced with different concentrations of MEL and with or without the addition of Tween® 80. Nanofibers morphology was evaluated by scanning electron microscopy. Thermal and spectroscopic analyses were performed to characterize the state of MEL in the scaffolds. MEL release profiles were observed under simulated physiological conditions (pH 7.4, 37 °C). The swelling behavior was evaluated by a gravimetric method. The results confirmed that submicron-sized nanofibrous structures were obtained with MEL in the amorphous state. Different MEL release rates were achieved depending on the nature of the polymer. Fast (20 min) and complete release was observed for the PVA-based samples, unlike the PLA polymer, which provided slow and controlled MEL release. The addition of Tween® 80 affected the swelling properties of the fibrous structures. Overall, the results suggest that membranes could be an attractive vehicle as a potential alternative to liquid formulations for ocular administration of MEL.

Innovation in the Development of Synthetic and Natural Ocular Drug Delivery Systems for Eye Diseases Treatment: Focusing on Drug-Loaded Ocular Inserts, Contacts, and Intraocular Lenses.

Nowadays, ocular drug delivery still remains a challenge, since the conventional dosage forms used for anterior and posterior ocular disease treatments, such as topical, systemic, and intraocular administration methods, present important limitations mainly related to the anatomical complexity of the eye. In particular, the blood-ocular barrier along with the corneal barrier, ocular surface, and lacrimal fluid secretion reduce the availability of the administered active compounds and their efficacy. These limitations have increased the need to develop safe and effective ocular delivery systems able to sustain the drug release in the interested ocular segment over time. In the last few years, thanks to the innovations in the materials and technologies employed, different ocular drug delivery systems have been developed. Therefore, this review aims to summarize the synthetic and natural drug-loaded ocular inserts, contacts, and intraocular lenses that have been recently developed, emphasizing the characteristics that make them promising for future ocular clinical applications.

Formulation development and in Vitro-Ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: Part I.

This study developed, optimized, characterized, and evaluated bioadhesive, hot-melt extruded (HME), extended-release ocular inserts containing ciprofloxacin hydrochloride (CIP-HCL) to improve the therapeutic outcomes of ocular bacterial infections. The inserts were fabricated with FDA-approved biocompatible, biodegradable, and bioadhesive polymers that were tuned in different ratios to achieve a sustained release profile. The results revealed an inverse relationship between the Klucel™ hydroxypropyl cellulose (HPC, 140,000 Da) concentration and drug release and extended-release profile over 24 h. The CIP-HCL-HME inserts presented stable drug content, thermal behavior, surface pH, and release profiles over three months of room-temperature storage and demonstrated adequate mucoadhesive strength. SEM micrographs revealed a smooth surface. Bacterial growth was not observed on the samples during the in vitro release experiment (0.5-24 h), indicating that a minimum inhibitory concentration (MIC) of 90 against Pseudomonas aeruginosa was achieved. Ex vivo transcorneal permeation studies using excised rabbit corneas revealed that the prepared ocular inserts prolonged the transcorneal flux of the drug compared to commercial eye drops and immediate-release inserts and could reduce the administration frequency to once daily. Therefore, the inserts could increase patient compliance and exhibited prolonged antibacterial activity and thus could provide better therapeutic outcomes against ocular bacterial infections.

An ocular insert with zero-order extended delivery: Release kinetics and mathematical models.

Ocular inserts (InEye®), were prepared based on two distinct formulations of PCL-PEG-PCL block copolymers - one with 33 % and the other with 24 % of PEG 600. Ring-open-polymerisation was used to link ε-caprolactone monomers to PEG hydroxyl end-groups. Molecular weight, PCL/PEG ratio, mass loss and swelling of different polymeric samples where determined. Based on the previously prepared block copolymers, ophthalmic inserts were assembled. These were prepared with an ellipsoidal shape by dripping melted polymer over a micro-tablet of moxifloxacin, used as drug model for this study, which therefore became entrapped in a central core coated with a polymer layer that functioned as a control-release barrier. The release kinetics of the model drug revealed a strong dependence on the PEG percentage on the polymer. Inserts' size and the amount of drug immobilized also had an important effect on the drug release profile. All release profiles followed a zero-order pattern, with 95 % of the drug being release at a constant rate. With drug releases varying from 20 to 200 days, and no initial burst, InEye® performance is unique among drug delivery systems and seems to be a very promising new formulation technology for preparing tailor-made ophthalmic inserts for prolonged and constant release of drug, which is needed for chronic diseases such as glaucoma, where compliance to treatment is essential for preventing optic-nerve lesions.

New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study.

A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open-angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests performed. In this sense, we also demonstrated that the treatment with the 50:50% insert can control the intraocular pressure (IOP) for at least 3 weeks and prevents damage to the retinal ganglion cells (RGCs) compared to the placebo insert. Thus, this indicates thus that the new drug is quite viable and promising in glaucoma treatment.

Sustained release of linezolid in ocular insert based on lipophilic modified structure of sodium alginate.

OBJECTIVES: Ocular inserts are usually polymeric thin films with increased ocular residence time and sustained drug release capacity. Sodium alginate is a biocompatible and biodegradable carrier; however, initial burst release of encapsulated drug within it, is recognized as a challenge. Grafting -addition of functional moieties to a polymer- is a technique to modify polymers' physicochemical properties, including higher ability to control drug release. Linezolid (LNZ) solution is used in consecutive doses in treatment of antibiotic-resistant Gram-positive bacterial infections especially induced by methicillin resistant Staphylococcus aureus (MRSA). MATERIALS AND METHODS: Grafted alginate copolymers were synthesized using butyl methacrylate (BMC) and lauryl methacrylate (LMC) at two different reaction times (12 hr and 24 hr). Copolymerization was evaluated by 1H-NMR, Ft-IR, and TGA. Copolymer safety was examined by cytotoxicity test against HEK-293 cell. Linezolid inserts were prepared using optimized copolymers and characterized. RESULTS: 1H-NMR, Ft-IR, and TGA confirmed the successful grafting of alginate copolymers. ALG-B24 and ALG-L12 showed the highest safety against HEK-293 cell line comparing with intact alginate. Linezolid insert characterization results indicated a slower linezolid release profile related to creation of a lipophilic structure. A better strength property for linezolid loaded ALG-B24 and ALG-L12 inserts was obtained while ALG-L12 showed a stronger adhesive force compared with intact alginate. Antibacterial efficacy on clinical isolated MRSA after 24 hr was similar to linezolid solution. CONCLUSION: Lipophilic alginate copolymer (ALG-L12) showed a sustained release capability while retaining its main feature in strong film forming ability so it seems to be a promising safe carrier.

Development, characterization, and ex vivo evaluation of an insert for the ocular administration of progesterone.

Progesterone (PG) affords neuroprotection in degenerative diseases associated to oxidative stress, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa. The aim of this project was to develop ocular inserts for delivery of PG to the eye. Different inserts with PG in its composition were formulated and the insert with the best characteristics (59% polyvinyl alcohol, 39% polyvinylpyrrolidone K30 and 2% propylene glycol) was selected for ex vivo studies. Physical characteristics and drug release patterns of the insert were analysed. In vitro diffusion studies revealed a controlled diffusion of progesterone. Ex vivo experiments demonstrated similar trans-corneal and trans-scleral PG diffusion (corneal apparent permeability coefficient 6.46 ± 0.38 × 10-7 cm/s and scleral apparent permeability coefficient 5.87 ± 1.18 × 10-7 cm/s; mean ± SD; n = 5). However, the amount of PG accumulated in scleras was statistically higher than in corneas (30.07 ± 9.09 µg/cm2 and 15.56 ± 4.36 µg/cm2 respectively). The PG-loaded inserts (55.6 µg/cm2) were thin, translucent, showed no irritancy (HET-CAM test) and were elastic and robust, all suitable properties for its potential use in the treatment of several ocular diseases.

Development and Characterization of a Novel Peptide-Loaded Antimicrobial Ocular Insert.

Infectious ocular keratitis is the leading cause of blindness worldwide. Bacterial resistance to classical pharmacological treatments raised the interest of researchers towards antimicrobial peptide (AMP)-based therapy. hLF 1-11, a synthetic antimicrobial peptide derived from the N-terminus of human lactoferrin, proved effective against different bacteria and yeast but, like all proteinaceous materials, it is unstable from chemical, physical, and biological points of view. In this study, new freeze-dried solid matrices containing mucoadhesive polymers were prepared and characterized in terms of rheology, hydration time, bioadhesion, drug content, and in vitro release. The formulation HPMC/T2/HA/hLF 1-11fd was selected for the delivery of hLF 1-11, since it showed good drug recovery and no chemical degradation up to at least 6 months (long-term stability). Furthermore, the HPMC/T2/HA/hLF 1-11fd matrix allowed for the release of the drug in a simulated physiological environment, linked to an optimal hydration time, and the peptide antimicrobial activity was preserved for up to 15 months of storage, a very promising result considering the chemical liability of proteinaceous material. For its properties, the freeze-dried matrix developed in this study could be a good platform for the delivery of antimicrobial peptides in the precorneal area to treat infectious phenomena of the ocular surface.

Microfibrillar polymeric ocular inserts for triamcinolone acetonide delivery.

Despite eye drops generally represent the most convenient, simple and patient-friendly formulations to treat ocular diseases, they suffer from poor retention on the ocular surface and low drug bioavailability leading to the necessity of prolonged and continuous treatment over time. Therefore, ocular insert could represent an innovative way to benefit from ocular topical administration while minimizing all the relevant limitation related to this route of administration. Polymeric non-erodible mucoadhesive ocular inserts should be comfortable and should rapidly adhere on the ocular surface, remain in situ for prolonged period, assure a reproducible and controlled drug release as well as act as transcorneal absorption promoters. In this study, a well-known aliphatic polyester, poly(1,4-butylene succinate) (PBS), was used as starting material to produce hydrophobic microfibrillar scaffolds by means of electrospinning technique. Plasma-assisted chemical surface functionalization of the PBS scaffolds with appropriate biopolymers (inulin, α,ß-poly(N-2-hydroxyethyl)-D,L-aspartamide, heparin) was carried out to confer to the final ocular inserts ad hoc properties as wettability, mucoadhesion and cytocompatibility on human corneal epithelial cells, by improving surface hydrophilicity without modifying the bulk properties of the material. The lipophilic drug triamcinolone acetonide was loaded into the obtained ocular insert and release studies were carried out to demonstrate the ability of drug loaded inserts to release the active until 30 days.

Cyclosporine-loaded cross-linked inserts of sodium hyaluronan and hydroxypropyl-ß-cyclodextrin for ocular administration.

This work aimed to develop cyclosporine ocular inserts combining sodium hyaluronate (HA) and hydroxypropyl-ß-cyclodextrin (HPßCD). Four different formulations, cross-linked with poly(ethylene glycol) diglycidyl ether, were studied to elucidate the role of the HA:HPßCD proportion on the physical characteristics and drug release patterns. The inserts (300 µm thickness) showed porous surfaces, high swelling ratios (∼10), and good cytocompatibility with fibroblasts and chorioallantoic membrane (HET-CAM test). Cyclosporine-loaded inserts (∼0.5% w/w drug content) appeared translucent. Release tests carried out under continuous flow of simulated lacrimal fluid revealed a controlled release of cyclosporine during the first 1 h. Conversely, differences among formulations were evidenced when the inserts were immersed in plenty volume of fluid; inserts with low content in HPßCD released the drug faster. These later inserts also facilitated cyclosporine accumulation into sclera (5.6-32.7 µgdrug/gsclera). Thus, cross-linked HA:HPßCD inserts appear as a suitable platform for peptide drug release to the ocular surface.

In vitro characterization of a controlled-release ocular insert for delivery of brimonidine tartrate.

Glaucoma is the second leading cause of blindness in the US. Brimonidine tartrate (BT) is a modern anti-glaucoma agent that is currently administered as frequently as a thrice-daily topical eye drop medication. Accordingly, compliance with BT regimens is low, limiting overall effectiveness. One attempt that has previously proved effective in addressing non-adherence is the formation of ocular inserts, such as the Ocusert(®), whose diffusion-based control released an older drug (pilocarpine) for a week-long period. Modern controlled drug-release technology provides an avenue for extending the release of practically any drug (including new drugs such as BT) for as long as 1 month from a singular insert. Currently, no controlled-release formulations for BT exist. This work outlines the development and characterization of a BT-releasing ocular insert designed from poly(lactic co-glycolic) acid/polyethylene glycol (PEG). It was found that a formulation containing 15% PEG can be created that produces a linear BT-release profile corresponding to BT eye drop delivery estimates. Additionally, these inserts were shown, through the use of atomic force microscopy and scanning electron microscopy, to have smooth surfaces and physical properties suitable for ophthalmic use.

Ocular insert for sustained delivery of gatifloxacin sesquihydrate: Preparation and evaluations.

BACKGROUND: Many polymeric systems have been used to fabricate ocular inserts for improve ocular bioavailability and retention to drug of which matrix systems have shown advantages of reduce dosing frequency and increased corneal residence time. The objective of the present investigation was to prepare and evaluate ocular inserts of gatifloxacin. MATERIALS AND METHODS: Ocular insert was made from an aqueous dispersion of gatifloxacin, sodium alginate, polyvinyl alcohol, and glycerin by solvent casting method. Ocular insert (5.5 mm) was cross-linked by CaCl(2) and was coated with Eudragit RL-100 or Eudragit RS-100. The ocular inserts were characterized for thickness; uniformity of weight, drug content uniformity, % moisture absorption or moisture loss, and surface pH. The in vitro diffusion studies were carried out by putting insert on Millipore membrane filter (0.8 µm) fixed between donor and receptor compartment of an all glass modified Franz diffusion cell. RESULTS: The thickness and drug content of ocular insert were found in the range of 0.11 ± 0.003 to 0.24 ± 0.010 mm and 0.718 ± 0.002 to 0.867 ± 0.007 mg, respectively. The surface pH, % moisture absorption or moisture loss and weight variation values were obtained in satisfactory range. The cross-linked ocular insert coated with Eudragit RL-100 shows maximum drug permeation i.e. 89.53 % ± 0.43 at 11 h. The stability studies suggest that all ocular insert remained stable, showed lesser degradation rate and maximum shelf life. CONCLUSION: Ocular inserts of gatifloxacin were prepared successfully by using solvent casting method for sustained drug delivery. The cross-linked and Eudragit RL-100 coated ocular insert of gatifloxacin provides better in vitro drug release and sustained upto 11 h.

Azithromycin novel drug delivery system for ocular application.

BACKGROUND: Azithromycin (AZT) is a macrolide antibiotic derived from and similar in structure to erythromycin. Oral administration of AZT is effective for the treatment of trachoma; however, topical formulations are difficult to develop because of the drug's hydrophobicity. The aim of this study is to formulate a novel topical ophthalmic delivery system of AZT. MATERIALS AND METHODS: In the present study, ocular inserts of AZT are prepared using alginate, carbopol, and hydroxypropyl methylcellulose (HPMC) to solve the said formulation problem of drug and to facilitate ocular bioavailability. Ocular inserts were prepared by film casting method and the prepared films were subjected to investigations for their physical and mechanical properties, swelling behaviors, ex vivo bioadhesion, and in vitro drug release. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test for ocular irritation potential. RESULTS: The physicochemical, bioadhesive, and swelling properties of films were found to vary significantly depending on the type of polymers used and their combinations. The alginate films exhibited greater bioadhesion and showed higher tensile strength and elasticity than the carbopol films. HPMC addition to the films significantly affected the properties of ocular inserts. Carbopol:HPMC (30:70)-based ocular inserts sustained drug release for longest span of 6 h. The release profile of AZT showed that drug release was by both diffusion and swelling. The formulation was found to be practically nonirritant in ocular irritation studies. CONCLUSION: AZT can therefore be developed as an ocular insert delivery system for the treatment of ocular surface infections.