Ocular Formulations Research Articles

Self-assembled hexagonal liquid crystalline gels as novel ocular formulation with enhanced topical delivery of pilocarpine nitrate

The aim of this paper was to develop hexagonal liquid crystalline (HII) gels that can be used as a novel ocular delivery system for pilocarpine nitrate (PN). HII gels were prepared by a vortex method using phytantriol/triglyceride/water (71.15: 3.85: 26, w/w) ternary system. The gels were characterized by crossed polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry and rheology. And, in vitro drug release behavior and ex vivo corneal permeation were investigated. Finally, preocular residence time evaluation, eye irritation test, histological examination and miotic tests were studied in vivo and compared with carbopol gel. Based on various characterization techniques, the inner structure of the gels were HII mesophase and exhibited a pseudoplastic fluid behaviour. In vitro release results revealed that PN could be released continuously from HII gel over a period of 24 h. The ex vivo apparent permeability coefficient of HII gel was 3.15-fold (P < 0.01) higher than that of the Carbopol gel. Compared with Carbopol gel, HII gel displayed longer residence time on the eyeballs surface using fluorescent labeling technology. Furthermore, the HII gel caused no ocular irritation was estimated by corneal hydration levels, Draize test and histological inspection. Additionally, in vivo miotic study showed that HII gel had a remarkably long-lasting decrease in the pupil diameter of rabbits. In conclusion, HII gels would be a promising sustained-release formulation for ocular drug delivery.

Formulation and Characterization of Glutathione-Loaded Bioadhesive Hydrogel for Ocular Delivery

Glutathione may prevent age-related, oxidative damage to ocular tissues but has poor corneal penetration. Hydrogel formulations were investigated to determine an optimized ocular delivery system. The rheology and texture profile of formulations were investigated at 25°C. The 1% w/v glutathione was incorporated into systems demonstrating desirable characteristics for ocular vehicles and physical characteristics re-determined. In vitro cumulative glutathione delivery across the bovine cornea was measured over 8 hours at 32°C in Franz diffusion cells. Carbopol-containing Poloxamer systems exhibited shear-thinning behavior desirable for ocular formulations whilst Polyvinyl alcohol (PVA) and Polyacrylic acid (PAA) systems exhibited Newtonian behavior. Of the glutathione-containing systems, 0.2% w/v Carbopol 1342 was the most viscous with a viscosity of 960 cP at a shear rate of 100 sec-1. All formulations significantly increased the amount of glutathione delivered across the cornea (relative to an aqueous solution of glutathione) with the exception of 0.1% w/v Carbopol 940 (p=0.12). Formulations containing 0.1% w/v Carbopol 934, 0.1% w/v Carbopol 1342 and 0.2% w/v Carbopol 940 improved penetration dramatically (ca. 30%); but were not significantly different from each other. Therefore, Carbopol and Poloxamer formulations demonstrated enhanced penetration of glutathione across the cornea. The 0.2% w/v C940-containing-Poloxamer formulation was determined to be the most promising drug delivery system for ocular delivery of glutathione.

FORMULATION, OPTIMIZATION, AND EVALUATION OF IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OPHTHALMIC DRUG DELIVERY

Objective: The present study emphasizes the synthesis, optimization, and evaluation of ocular in-situ gel for ophthalmic drug delivery against conjunctivitis.&#x0D; Methods: Pre-formulation studies on the drug and polymers were carried out, which included the study of various physicochemical properties of the drug and drug-polymer compatibility studies. The 12 different formulations were further pre-optimised by Taguchi method for determining the number of influential factors. Furthermore, the formulation optimization was done by using ‘Box–Behnken’ design (BBD) (Design expert 10 software) for assessing the effect of formulation variables on product characteristics viz. viscosity, gelation temperature (GT), and mean release time (MRT). About 13 suggested runs of the experiment were carried out and formulations were optimised. Finally, three batches of the optimised formulation were prepared and evaluated for in vitro drug release, isotonicity of formulation, anti-microbial potential, ocular irritancy, and accelerated stability testing.&#x0D; Results: Pre-formulation study confirmed the purity, solubility, and compatibility of drug measured by λmax, partition coefficient, stability study, and Fourier-transform infrared spectroscopy (FTIR) analysis. Taguchi screening method suggested about 12 different formulations and 3 most prominent influential factors including viscosity, GT, and drug release. 13 different formulations designed based on ‘BBD’ method were further optimised by considering the most influential factors suggested by Taguchi screening. The in vitro evaluation of the optimised formulation gave satisfactory results in terms of drug release, and anti-microbial activity. It was found to be isotonic with no ocular irritancy. Further, the preparation immediately transformed from sol to gel upon administration into cul-de-sac region of the eye due to multi-dimensional approaches utilised for in-situ gel formation namely temperature change Pluronic, ion sensitivity due to Gellan-gum, pH sensitivity because of Carbopol.&#x0D; Conclusion: The optimised in-situ gelling ocular drug formulation showed promising potency for ophthalmic drug delivery with no irritancy due to the multifactorial mechanism.

Pharmacognostical and Phytochemical Evaluation of Pilla Shukra Nashaka Anjana Varti – an ocular Ayurvedic Formulations

Pharmacognostical and Phytochemical Evaluation of Pilla Shukra Nashaka Anjana Varti – an ocular Ayurvedic Formulations

Comprehensive review of ophthalmic drug delivery systems for effective antibiotic therapy

Background: Ophthalmic drug delivery presents a unique challenge due to the complexity of ocular anatomy and the barriers to drug absorption. Current ocular formulations struggle with issues such as low bioavailability and rapid drug elimination, necessitating advancements in drug delivery systems to enhance therapeutic efficacy. Aim: This review aims to evaluate various ophthalmic drug delivery systems specifically for antibiotic therapies, addressing their efficacy in overcoming ocular barriers and improving drug retention. Methods: A comprehensive literature review was conducted, focusing on different ophthalmic drug delivery systems including topical formulations (eye drops, ointments, hydrogels, and contact lenses), novel systems (in situ gels, nanoparticles, and emulsions), and advanced techniques like intraocular injections. Key developments and challenges associated with each method were analyzed to assess their impact on drug bioavailability and therapeutic outcomes. Results: Traditional ophthalmic delivery methods, such as eye drops and ointments, are limited by factors such as rapid drug clearance and poor bioavailability. Innovations such as in situ gelling systems, nanoparticles, and emulsions have shown promise in extending drug residence time and enhancing bioavailability. Specifically, nanoparticles offer targeted delivery and prolonged action, while hydrogels and emulsions improve drug solubility and stability.

Preparation and characterization of novel, mucoadhesive ofloxacin nanoparticles for ocular drug delivery

The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation, resulting in low ocular bioavailability. Mucoadhesive chitosan (CS)/ tripolyphosphatesodium (TPP) and chitosan (CS)/ tripolyphosphatesodium (TPP)-alginate (ALG) nanoparticles were investigated for the prolonged topical ophthalmic delivery of ofloxacin. A modified ionotropic gelation method was used to produce ofloxacin-loaded nanoreservoir systems. The ofloxacin-loaded CS/TPP and CS/TPP-ALG nanoparticles were characterized for particle size, morphology, zeta potential, encapsulation efficiency, subsequent release and corneal penetration study. The designed nanoparticles have a particle size from 113.8 nm to 509 nm and zeta potential from 16.2 mV to 40.3 mV and encapsulation efficiency values ranging from 19.7% to 33.1%. Nanoparticles revealed a release during the first hours, followed by a more gradual drug release. The ofloxacin-loading CS/TPP or CS/TPP-ALG NPs developed are pronounced penetration enhancing effect as compared to OFX solution (5-6.5 times). Thus, these nanoparticles have a strong potential for ocular drug delivery.

Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication

Glaucoma treatment with ocular medications requires overcoming the corneal barrier to drug penetration. Liposomes have a great corneal penetration ability and affinity while suffering from poor stability and low entrapment of hydrophilic drugs accompanied by rapid drug release. This work aims to develop a new, effective and stable glaucoma medication with sustained drug release properties; Timolol maleate gelatinized core liposomes. A full factorial design was utilized to study the effects of three formulation variables on drug loading and vesicle particle size. Vesicles were prepared by the thin-film hydration method, and characterized for in-vitro drug release and stability. Intra-ocular pressure (IOP) reduction was evaluated in-vivo on glaucomatous rabbit’s eyes. The safety profile was assessed using histopathological examinations. Gelatin significantly increased the drug entrapment percentage reaching 50% with a particle size of 38.81 µm. Sustained drug release was recorded compared to a marketed product and to a conventional liposomal formulation. The prepared vesicles caused the highest reduction in IOP accompanied by safe histological findings. This work provided a new, safe and effective ocular glaucoma medication; Timolol maleate gelatinized core liposomes, solving the main problems of ocular liposomal formulations of hydrophilic drugs, suitable for the pharmaceutical industry and comprising abundant and relatively cheap components.

Pharmacognostical and Phytochemical Evaluation of Gutika Anjana - An Ocular Ayurvedic Formulation

Pharmacognostical and Phytochemical Evaluation of Gutika Anjana - An Ocular Ayurvedic Formulation

DEVELOPMENT AND EVALUATION OF CIPROFLOXACIN HYDROCHLORIDE LOADED OCULAR INSERT BY USING “PLANTAGO OVATA” AS NATURAL POLYMER

Objective: The present work focus in the direction of “Development and evaluation of Ciprofloxacin Hydrochloride loaded ocular insert by using “plantago ovata” as natural polymer”. The current work was carried out to evaluate the control release profile of ocular insert. Natural polymer in ocular insert was used for studying the long acting property. Natural polymer is also used to enhance the bioavailability of drug and reduce toxicity. It is also used to increase the duration of action of drug for prolongs action and gives better in vitro performance as compare than to the conventional ocular formulation.Methods: Solvent casting method was used in the formulation of Ciprofloxacin Hydrochloride loaded ocular inserts. Different ocular insert formulations of varying polymer concentration were prepared. Ocular insert formulation H-1 to H-3 was prepared by using different concentration of HPMC and formulation P-1 to P-4 was prepared by using different concentration of Plantago Ovata.Results: The ocular inserts formulation was within the acceptable limits. All the pre formulation parameters of polymers such as derived properties, compressibility index, Hausner’s ratio, viscosity, melting point, swelling ratio, loss on drying, PH of mucilage solution and pre formulation of active pharmaceutical ingredient such as estimation of drug by using UV spectroscopy, determination of melting point, solubility, partition coefficient and FTIR for compatibility study of drug and excipient were evaluation. FTIR analysis also confirmed no drug-excipient interaction.Conclusion: Prepared inserts in the present study were semitransparent. The mixing of the drug in to the polymer is uniform, due to this; the drug content of all formulation is good. Formulation P4 was selected because it showed better release profile, drug content and other physicochemical properties than other formulated batch when compare. All the prepared inserts showed in vitro drug release for the period of 4 h as compare to the marketed formulation. An in vitro drug release study revealed that ocular formulation gives a prolong action. The formulation was found to be long acting.

Biodegradable Microspheres as Intravitreal Delivery Systems for Prolonged Drug Release. What is their Eminence in the Nanoparticle Era?

Drug administration to the posterior segment of the eye has many challenges due to the natural barriers and consequent problems of low and unpredictable bioavailability. There is an increasing need for managing severe posterior eye diseases, such as age-related macular degeneration, diabetic retinopathy, etc. Most of these diseases, if left untreated, lead to blindness. Traditional ocular formulations and topical administrations are almost inefficient and the drug delivery to the back of the eye requires direct administrations through intravitreal injections of innovative drug delivery systems. These systems must be easily injectable, able to release the drug for a prolonged period of time (to overcome the problem of repeated administrations) and made of biodegradable/biocompatible polymers. Among these delivery systems, microspheres still have an important role. This overview wants to highlight the use of microspheres as intravitreal systems to overcome the challenges of back of the eye diseases. Studies have shown that microspheres are able to enhance the intravitreal half-life and thus bioavailability of many drugs, protecting them from degradation. Furthermore, personalized therapies can be made by changing the amount of administered microspheres. This review focuses on the materials (polymers) used for the preparation of the microparticulate systems and comparative remarks are made with respect to the use of nanoparticles.

Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.

Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only available as 0.1% ophthalmic suspension (Nevanac®). This study utilized hydroxypropyl-β-cyclodextrin (HPBCD) to increase the water solubility and trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the liquid and solid states were confirmed by phase solubility, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses. Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and osmolality as that of Nevanac®) and pig eye trans-corneal permeation was studied versus Nevanac®. Furthermore, nepafenac content in cornea, sclera, iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was studied in a continuous isolated pig eye perfusion model in comparison to the suspension and Nevanac®. Permeation studies using porcine corneas revealed that the solution formulation had a permeation rate 18 times higher than Nevanac®. Furthermore, the solution had 11 times higher corneal retention than Nevanac®. Drug distribution studies using porcine eyes revealed that the solution formulation enables detectable levels in various ocular tissues while the drug was undetectable by Nevanac®. The ocular solution formulation had a significantly higher drug concentration in the cornea compared to the suspension or Nevanac®.

LC–MS analysis to determine the biodistribution of a polymer coated ilomastat ocular implant

Ilomastat is a matrix metalloproteinase inhibitor (MMPi) that has shown the potential to inhibit scarring (fibrosis) by mediating healing after injury or surgery. A long lasting ocular implantable pharmaceutical formulation of ilomastat is being developed to mediate the healing process to prevent scarring after glaucoma filtration surgery. The ilomastat implant was coated with water permeable and biocompatible phosphoryl choline polymer (PC1059) displayed extended slow release of ilomastat in vitro and in vivo. The ocular distribution of ilomastat from the implant in rabbits at day 30 post surgery was determined by the extraction of ilomastat and its internal standard marimastat from the ocular tissues, plasma, aqueous humour and vitreous fluid followed by capillary-flow liquid chromatography (cap-LC), the column effluent was directed into a triple quadrupole mass spectrometer operating in product scan mode. The lower limits of quantification (LLOQs) were 0.3 pg/μL for ocular fluids and plasma, and 3 pg/mg for ocular tissues. The extraction recoveries were 90–95% for ilomastat and its internal standard from ocular tissues. Ilomastat was found in ocular fluids and tissues at day 30 after surgery. The level of ilomastat was 18 times higher in the aqueous humour than vitreous humour. The concentration ranking of ilomastat in the ocular tissues was sclera > bleb conjunctiva > conjunctiva (rest of the eye) > cornea. Mass spectrometry analysis to confirm the presence of ilomastat in the ocular tissues and fluids at day 30 post-surgery establishes the extended release of ilomastat can be achieved in vivo, which is crucial information for optimisation of the ilomastat coated implant.

FORMULATION AND OPTIMIZATION OF THERMOSENSITIVE IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OCULAR DRUG DELIVERY

Objective: The present study has focused on development and optimization of thermosensitive in-situ ocular drug delivery system for the treatment of conjunctivitis.Methods: Thermosensitive in-situ hydrogel formulation of moxifloxacin hydrochloride was developed by dispensing variable concentration of pluronic F-127, gellan-gum, and carbopol in distilled water. Viscosity, gelation temperature and mean release time (MRT) were measured by using ‘Brookfield' viscometer LV-III (spindle no. 40), rheological techniques and dissolution apparatus respectively. Optimization for ideal formulation was carried by ‘Box–Behnken' design on the basis of prime factors of the formulation including viscosity, gelation temperature, and MRT. Moreover, the optimized formulation was evaluated for accelerated stability study by in vitro drug release, anti-microbial potential by ‘Kirby-Bauer disk diffusion' method and ocular irritancy assay were done by in vivo analysis.Results: Optimised thermosensitive in-situ gel, when administered into cul-de-sac region of the eye, it was immediately transformed from sol to gel by multi-dimensional mechanism due to plurionic, gellan-gum, carbopol. The optimized formulation minimizes the chances of formulation failure as well as the concentration on individual polymer which dependence on a single mechanism of gelation. The final optimised formulation consists of plurionic (11.50% w/v), gellan-gum (0.32% w/v), carbopol (0.3% w/v), shows optimum therapeutic effect. Moreover, the accelerated stability study, anti-microbial potential, and ocular irritancy confirmed the biocompatibility of optimized in-situ drug-containing gel with high potency and stability.Conclusion: Thus, optimized in-situ drug-containing gel with multifactorial approaches showed promising ocular formulation having minimum side effect and high therapeutic efficacy.Â

In-vitro Drug Release and Ex-vivo Corneal Permeation of Dexamethasone and Curcumin Nanodispersions Using Facilitated Simultaneous RP-HPLC Technique

Since the designs of optimal ocular nanodispersion formulations for dexamethasone and curcumin permeation via the cornea are lacking, the aim of this study was to establish the corneal permeability of dexamethasone and curcumin across goat eyes. For that, a facilitated RP-HPLC method with PDA detection has been developed and validated for the simultaneous estimation of dexamethasone and curcumin. The chromatographic estimation was achieved using Eclipse XDB C8 analytical column and the mobile phase consisting of acetonitrile: water (42: 58 % v/v) run at a flow rate of 1.0 mL/min with an injection sample volume of 200 μL. The UV detection was carried out at 281 nm using PDA detector. The developed method was able to separate the drug peaks with retention time of 3.5 and 10.8 min for the dexamethasone and curcumin, respectively. The method was validated for its linearity, system precision, method precision, analyst variation, inter/ intraday variations, detection limits and robustness. Hence the developed method was found to be selective and sensitive as both peaks were well separated with a moderate analysis time and could be used for the routine analysis in drug developmental research.

Effects of chitosan and chitosan N-acetylcysteine solutions on conjunctival epithelial cells

# Aim of the study Chitosan, a partially deacetylated polysaccharide derived from chitin, and chitosan-N-acetylcysteine (C-NAC), a thiolated chitosan, both show enhanced retention times on the ocular surface when compared to other polymers commonly used in eye drops. To evaluate these compounds as adjuvants for ocular drug delivery or uptake of topically administered conjunctival vaccines, biochemical characteristics of both polymers were investigated in vitro and in vivo. # Methods Human conjunctival epithelial (HCjE) cells were used to investigate biocompatibility of buffered chitosan and C-NAC containing formulations. Cellular uptake was studied using fluorescein-isothiocyanate (FITC)-labelled polymers. Transepithelial electrical resistance (TEER) measurements were performed to determine effects of chitosan on tight junctions of stratified HCjE cells in vitro. In vivo uptake of topically applied chitosan into conjunctival epithelial cells was investigated in guinea pigs. # Results Minimal effects on cell viability were seen with both compounds after application for 30 min in a concentration of 0.1%. In vitro uptake into HCjE cells was only observed with the chitosan containing solution. An effect on tight junctions was demonstrated by significantly (P < .05) decreasing TEER levels 60 min after incubation with chitosan. In vivo, FITC-labelled chitosan was detected within guinea pig conjunctival epithelial cells 120 min after topical administration. No adverse effects were observed. # Conclusions Results demonstrated that chitosan is taken up into conjunctival epithelial cells in vitro and in vivo, therefore fulfilling some of the requirements of an adjuvant for conjunctival mucosal vaccines. C-NAC is also well tolerated but not taken up by cells, making it a good candidate for ocular formulations supposed to persist on the ocular surface for an extended period of time.

Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery

A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk biodegradable hydrogel made from triblock copolymers with poly(ethylene glycol) (PEG) center blocks and hydrophobic biodegradable polyester blocks such as poly(lactide-co-glycolide) (PLGA), Poly(lactic acid) (PLA), or Poly(lactide-co-caprolactone) (PLCL) blocks. This system is engineered to flow as a liquid solution at room temperature for facile injection into the eye and then quickly gel as it warms to physiological body temperatures (approximately 37 °C). The hydrogel acts as an ocular depot that can release three different drug molecules at programmed rates and times to provide optimal release of each species. In this manuscript, the hydrogel is configured to release a broad-spectrum antibiotic, a potent corticosteroid, and an ocular hypotensive, three ophthalmic therapeutic agents that are essential for post-operative management after ocular surgery, each drug released at its own timescale. The delivery platform is designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Hydrophobic blocks, such as PLCL, were utilized to prolong the release duration of the biomolecules. This system also enables customization by being able to vary the initial drug loading to linearly tune the drug dose released, while maintaining a constant drug release profile over time. This minimally invasive biodegradable multi-drug delivery system is capable of replacing a complex ocular treatment regimen with a simple injection. Such a depot system has the potential to increase patient medication compliance and reduce both the immediate and late term complications following ophthalmic surgery. Statement of SignificanceAfter ocular surgery, patients routinely receive multiple medications including antibiotics, steroids and ocular hypotensives to ensure optimal surgical outcomes. The current standard of care for postoperative treatment after ocular surgery involves using eye drops daily, which has limited effectiveness mainly due to poor patient adherence. To improve patient experience and outcomes, this article presents the first thermoresponsive hydrogel able to release multiple drug molecules for the application of post-operative treatment following ocular surgery. By varying the parameters such as hydrogel type and polymer hydrophobicity, the drug release profile, duration and dosage can finely be tuned. The approach presented in this article can readily be applied to other applications by simply changing the drug loaded in the drug delivery system.

Supramolecular nanofibers of dexamethasone derivatives to form hydrogel for topical ocular drug delivery.

The low bioavailability exhibits by conventional ocular formulation owing to rapid precorneal clearance and lower corneal permeability can be overcame by the application of the gelling system. In the present study, a prodrug supramolecular hydrogel derived from succinated dexamethasone (Dex-SA) was fabricated using a pH hydrolytic strategy and explored as a "self-delivery" system for ophthalmic drugs. The self-assembled Dex-SA supramolecular hydrogel exhibited a typical nano-fibrous microstructure and was thixotropic. Both dexamethasone (Dex) and Dex-SA prodrug sustainably released from Dex-SA supramolecular hydrogel in a period of 120 h in vitro release study, and the initial pH value of hydrogel significantly influence on the release ratio of Dex/Dex-SA. Furthermore, the lyophilized Dex-SA supramolecular hydrogel displayed long-term stability without causing any apparent hydrolysis of Dex-SA at -20 °C over 30 day and quickly re-formed a hydrogel after dissolving into aqueous solution. The formed Dex-SA supramolecular hydrogel had lower cytotoxicity than Dex at drug concentration up to 2.5 mM, and exhibited a comparable anti-inflammatory efficacy to a Dex sodium phosphate (Dexp) aqueous solution in lipopolysaccharide-activated RAW264.7 macrophages. Topical instillation of the Dex-SA supramolecular hydrogel showed excellent intraocular biocompatibility and it was not an irritant in rabbit eyes. More importantly, the Dex-SA supramolecular hydrogel provided a prolonged precorneal retention and significantly enhanced the ocular bioavailability over Dexp aqueous solution after topical instillation. Overall, this work illustrates an effective approach for the development of prodrug supramolecular hydrogels to extend the precorneal retention and enhance ocular bioavailability of drugs after topical instillation.

Ocular Drug Delivery and Novel Formulations: A Review

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.

Methods for Testing Ocular Toxicity: Current Status

The developed ophthalmic formulations should be tested for ocular toxicity testing like draize eye test. Rapid growth in the field of ocular toxicity testing replaces the usage of animals and to adopt the modified protocols. The researchers have to develop properly validated and regulatory approved options to animal testing. Alternative ocular toxicity testing is based on corneal structure and mechanism through which the specific ocular formulation causes irritation to the eyes. Several alternative assay methods have been introduced in the field of ocular toxicity testing like in vitro organotypic model for testing ocular toxicity and several other methods like Bovine Corneal Opacity and Permeability Assay (BCOP Assay), isolated chicken eye test, isolated rabbit eye test and Hen's egg-test on the chorioallantoic membrane. The ultimate aim of alternate methods of ocular toxicity testing is to develop properly validated and regulatory approved best practices. Hence this review highlights the development in the field of alternative ocular toxicity testing methods.

Chitosan Nanoparticles as a Mucoadhesive Drug Delivery System for Ocular Administration.

Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs’ bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (∆η). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.