Conventional Eye Drops Research Articles

Handling Test of Eye Drop Dispenser—Comparison of Unit-Dose Pipettes with Conventional Eye Drop Bottles

The aims of this study were to investigate how elderly people handle single-use eye drop dispensers (unit-dose pipettes) and to compare the performance with conventional eye drop bottles. In this open-label study, the handling of unit-dose pipettes and conventional eye drop bottles was compared in 41 elderly people who had little or no prior regular use of eye drop dispensers. The participants tested both types of dispenser once, and the following 7 variables were studied: ease/difficulty of opening the dispenser; influence of the size for handling of the dispenser; influence of the shape for handling of the dispenser; observation of the contents in the dispenser; the feeling of the dispenser in the hand; ease/difficulty of drop instillation on the eye from the dispenser; and overall performance of the eye drop dispenser. The dispensers contained isotonic saline, and a visual analog scale was used for assessment of each of the above variables. The mean age of the participants was 73 years. A statistically significant difference in favor of the unit-dose pipettes was found with respect to observation of the contents in the dispenser, ease of administration, and the overall performance. Women regarded the unit-dose pipettes generally better than the bottles, but such a difference was not seen in men. The study participants managed the unit-dose pipettes at least as well as the conventional eye drop bottles. If anything, the unit-dose pipettes appeared to be easier to use.

Ion- and pH-activated novel in-situ gel system for sustained ocular drug delivery

Poor bioavailability (<1%) of drugs from conventional eye drops is mainly due to the various precorneal loss factors which include rapid tear turnover, systemic drug absorption through naso-lachrymal duct, transient residence time of the drug solution in the cul-de-sac and the relative impermeability of the drugs to corneal epithelial membrane. The present study describes the formulation and evaluation of chitosan and gellan gum based novel in-situ gel system activated by dual physiological mechanisms. Chitosan (a pH-sensitive polymer) in combination with gellan gum (an ion-activated polymer) were used as gelling agent. Timolol maleate, the drug which is frequently used for glaucoma therapy was used as model drug to check the efficacy of the formulation. The developed formulation was characterized for various in vitro parameters, for example, clarity, gelation pH, isotonicity, sterility, viscosity, transcorneal permeation profile, and ocular irritation. Ocular retention was studied by gamma scintigraphy and a significant increase in retention time was observed. The formulation was also found to be nonirritant and well tolerable. The developed system can be a viable alternative to conventional eye drops for the treatment of various ocular diseases and is suitable for clinical application.

Carbopol/Chitosan Based pH Triggered In Situ Gelling System for Ocular Delivery of Timolol Maleate

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic preparations due to rapid precorneal elimination, dilution and nasolacrimal drainage of the drug may be vanquished by the use of in situ gelling systems that are instilled as drops in to the eye and undergo a sol-gel transition in the cul-de-sac. Timolol eye drops may cause systemic side effects in glaucoma patients due to absorption of the drug into systemic circulation. In situ gelling system of this drug can provide localized effect with reduced contraindications, improved patient compliance and better therapeutic index. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antiglaucoma drug, timolol maleate (TM) based on the concept of pH-triggered in situ gelation. Polyacrylic acid (carbopol) was used as the gelling agent in combination with chitosan (amine polysaccharide), which was acted as a viscosity-enhancing agent. Formulations were evaluated for pH, viscosity, gelling capacity and drug content. The 0.4% w/v carbopol/0.5% w/v chitosan based in situ gelling system was in liquid state at room temperature and at the pH formulated (pH 6.0) and underwent rapid transition into the viscous gel phase at the pH of the tear fluid (lacrimal fluid) (pH 7.4). The in vitro drug release and in vivo effects of the developed in situ gelling system were compared with that of Glucomol® (a 0.25% TM ophthalmic solution), 0.4% w/v carbopol solution as well as liposomal formulation. The results clearly demonstrated that developed carbopol-chitosan based formulation was therapeutically efficacious and showed a fickian (diffusion controlled) type of release behaviour over 24 h periods. The developed system is thus a viable alternative to conventional eye drops and can also prevent the rapid drainage as in case of liposomes.

Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery

Poor ocular bioavailability of drugs (<1%) from conventional eye drops (ie, solution, suspension, and ointments) is mainly due to the physiologic barriers of the eye. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. In our current work, we develop and evaluate a new colloidal system, that is, poly(dl-lactide- co-glycolide) (PLGA) nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal residence time and ocular penetration. Nanoparticles were prepared by nanoprecipitation technique and characterized for various properties such as particle size, zeta potential, in vitro drug release, statistical model fitting, stability, and so forth. Microbiological assay was carried out against Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was studied in albino rabbits by gamma scintigraphy after radiolabeling of sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The developed nanosuspension showed a mean particle size in the range of 180 to 190 nm, suitable for ophthalmic application with zeta potential of –22 mV. In vitro release from the developed nanosuspension showed an extended release profile of sparfloxacin according to the Peppas model. Acquired gamma camera images showed good retention over the entire precorneal area for the developed nanosuspension compared with that of a marketed formulation. The marketed drug formulation cleared very rapidly from the corneal region and reached the systemic circulation through the nasolacrimal drainage system, as significant radioactivity was recorded in kidney and bladder after 6 hours of ocular administration, whereas the developed nanosuspension cleared at a very slow rate ( P < .05) and remained at the corneal surface for longer duration, as no radioactivity was observed in the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the nonirritant property of the developed nanosuspension. The developed lyophilized nanosuspension was found to be stable for a longer duration of time than the conventional marketed formulation with a good shelf life. From the Clinical Editor Poor ocular bioavailability of drugs (<1%) from conventional eye drops is mainly due to the eye physiological barriers. In this study, a new colloidal system, PLGA nanoparticle for sparfloxacin ophthalmic delivery was demonstrated to improve precorneal residence time and ocular penetration. The developed lyophilized nanosuspension was found to be stable for longer duration of time than conventional marketed formulations.

Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studies

AbstractMost ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol‐to‐gel transition in the cul‐de‐sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti‐inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH‐triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E15LV), which acted as a viscosity enhancer. The prepared formulations were characterized for clarity, pH, drug content, rheology, and in vivo drug release. Clarity, pH, and drug content of the developed formulations were found to be satisfactory. The developed formulation showed pseudo‐plastic rheology. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also importantly is the ease of instillation afforded and decreased frequency of instillation resulting in better patient acceptance. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.

Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.

Development and Characterization of 99mTc-timolol Maleate for Evaluating Efficacy of In Situ Ocular Drug Delivery System

In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive technique. For scintigraphy study, the drug timolol maleate was radiolabeled (99m)Tc by direct labeling method using SnCl(2).2H(2)O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug ((99m)Tc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images and the time-activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test and formulation was found to be practically nonirritant. The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner.

A Single Intraoperative Sub-Tenon’s Capsule Injection of Triamcinolone and Ciprofloxacin in a Controlled-Release System for Cataract Surgery

To compare intraoperative injection of triamcinolone and ciprofloxacin in a controlled-release system (DuoCat) with prednisolone and ciprofloxacin eye drops after cataract surgery. In this randomized, double-masked, controlled trial, a total of 135 patients undergoing cataract surgery were randomly allocated to two groups: 67 patients treated after surgery with prednisolone 1% and ciprofloxacin 3% eye drops four times daily (week 1), three times daily (week 2), twice daily (week 3), and once daily (week 4) and 0.3% ciprofloxacin drops four times daily (weeks 1 and 2), and 68 patients treated at the end of surgery with a sub-Tenon's injection of 25 mg triamcinolone and 2 mg ciprofloxacin in biodegradable microspheres. The patients were examined on postoperative days 1, 3, 7, 14, and 28. The main outcome measures were postoperative anterior chamber cell and flare, intraocular pressure (IOP), lack of anti-inflammatory response, and presence of infection. No significant differences were observed between the groups in anterior chamber cell (P > 0.14) and flare (P > 0.02) at any postoperative visits. The mean (99% confidence interval) differences in IOP between the prednisolone and triamcinolone groups on days 1, 3, 7, 14, and 28 were -0.4 mm Hg (-2.1 to 1.3), 0.0 mm Hg (-1.4 to 1.3), 0.0 mm Hg (-1.1 to 1.1), -0.2 mm Hg (-1.1 to 0.8), and -0.1 mm Hg (-1.1 to 0.9), respectively. No patient had a postoperative infection. One injection of DuoCat had a therapeutic response and ocular tolerance that were equivalent to conventional eye drops in controlling inflammation after cataract surgery. (ClinicalTrials.gov number, NCT00431028.).

Fluoroquinolones compared to 1% azithromycin in DuraSite&amp;reg; for bacterial conjunctivitis [from Lichenstein and Granet] and Response to correspondence [from Friedlaender and Protzko] ||FREE PAPER||

Fluoroquinolones compared to 1% azithromycin in DuraSite&amp;reg; for bacterial conjunctivitis [from Lichenstein and Granet] and Response to correspondence [from Friedlaender and Protzko] ||FREE PAPER||

Modelling ocular pharmacokinetics of fluorescein administered as lyophilisate or conventional eye drops

The objective of this evaluation was to model ocular pharmacokinetics of fluorescein administered as conventional eye drops and as lyophilisate to healthy volunteers in order to assess the relative bioavailability of the lyophilisate formulation. A total of 44 healthy subjects received equivalent doses of fluorescein as lyophilisate to one eye and as eye drops to the fellow eye in three individual studies. Fluorescein concentrations in the cornea and anterior chamber were measured by fluorophotometry. Data were analyzed by noncompartmental methods (WinNonlin software) and by compartmental population pharmacokinetic methods (NONMEM software). Compared to eye drops, both maximum fluorescein concentrations (C(max)) and the areas under the concentration-time curve (AUC(0-t )) values of fluorescein in the cornea and anterior chamber for lyophilisate were increased in the noncompartmental analysis: mean lyophilisate C(max) in the studies was 6.3- to 14.6-fold higher and mean AUC(0-t ) was 4.7- to 8.9-fold higher for ocular concentrations in the three studies. A three-compartment open model with first-order elimination from the anterior chamber adequately described population data. Estimated fluorescein systemic bioavailability (F) via the ocular route from lyophilisate relative to eye drops was 3.7-fold higher (95% CI 2.6-4.8). The data clearly show a considerably superior intraocular bioavailability of fluorescein when given as lyophilisate compared to conventional eye drops. There is a clear pharmacokinetic advantage of the lyophilisate preparation.

Ocular Poloxamer-Based Ciprofloxacin Hydrochloride In Situ Forming Gels

The purpose of this study was to develop poloxamer-based in situ gelling formulations of ciprofloxacin hydrochloride (HCl) aiming at prolonging corneal contact time, controlling drug release, enhancing ocular bioavailability, and increasing patient compliance. The in situ forming gels were prepared using different concentrations of poloxamer 407 (P407) and poloxamer 188 (P188). Mucoadhesives such as hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were added to the formulations to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their in vitro drug release, sol–gel transition temperature, rheological behavior, and mucoadhesion force. The in vivo antimicrobial efficacy of selected ciprofloxacin HCl in situ gelling formulations was studied on infected rabbit's eyes and compared with that of the marketed conventional eye drops. The gelation temperature of the prepared formulations ranged from 28.00 to 34.03°C. Increasing the concentrations of P407, HPMC, and HEC increased the viscosity and mucoadhesion force of the preparations and decreased the in vitro drug release. Ciprofloxacin HCl in situ forming gel formulae composed of P407/P188/HPMC (18/13/1.5%, wt/wt), and P407/P188/HEC (18/13/0.5%, wt/wt) showed optimum release and mucoadhesion properties and improved ocular bioavailability as evidenced by an enhanced therapeutic response compared with the marketed conventional eye drops.

Gelrite‐Based In Vitro Gelation Ophthalmic Drug Delivery System of Gatifloxacin

The conventional ophthalmic solutions have demonstrated poor bioavailability and low therapeutic response due to rapid precorneal elimination of drug, which could be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol‐gel transition in the cul‐de‐sac. The present work describes the formulation of an ophthalmic delivery system of an antibacterial agent, Gatifloxacin, based on the concept of ion‐activated in situ gelation; the rheological properties of the formulation and in vitro release of the drug were evaluated. Gelrite gellan gum, a novel vehicle for ophthalmic delivery system, which gels in the presence of mono/divalent cations present in the tear fluid, was used as the gelling agent. The developed formulation showed pseudoplastic rheology and was therapeutically efficacious and provides sustained release of the drug over a 12‐hour period. The developed system is thus a viable alternative to conventional eye drops.

Mucoadhesive microparticles engineered for ophthalmic drug delivery

Although topical drug delivery is a convenient route of administration to treat various eye diseases, it has serious limitations due to rapid clearance of the formulation from the surface of the eye. In this study, we engineered microparticles for both sustained drug delivery and prolonged residence time on the extraocular surface. Microparticles were fabricated by emulsification using poly(lactic- co-glycolic acid) (PLG) and poly(ethylene glycol) (PEG) as the core material and mucoadhesion promoter, respectively. The particle size was controlled to be less than 10 μm to avoid eye irritation and for eventual clearance through the lacrimal canals. In vitro mucoadhesion tests showed that PLG microparticles with PEG adhered better to the mucous membrane under the conditions employed in this study compared to the microparticles without PEG. When an aqueous suspension of microparticles with PEG was administered topically to the rabbit eye in vivo, microparticles were seen for up to 30 min on the ocular surface in the cul-de-sac, which was a dramatic increase in residence time as compared to conventional eye drop formulations. We conclude that mucoadhesive microparticles are promising vehicles for ophthalmic drug delivery.

This issue of Acta

The cover photograph shows enhanced optical coherence tomography (OCT) and comes from the article by Soliman et al. in this issue. Costa and Arcieri review hypotony maculopathy, including the definition, mechanisms, clinical findings and treatment of this condition. The editorial discusses the physiological consequences of hypotony in light of Starling’s law. Sigurðsson et al. in Iceland show that topical application supplies steroids in significant concentration to the posterior segment of the rabbit eye and suggest that the topical route may replace intravitreal injections in steroid treatment for retinal disease. Paccola et al. in Brazil and the USA demonstrate that postoperative inflammation after vitrectomy may be controlled either by a single subtenon injection of triamcinolone or by conventional prednisolone eye drops. Khanna et al. in India describe 48 patients with histologically confirmed sarcoidosis involving the eye, more frequently as posterior than anterior uveitis. Soliman et al. in Copenhagen use enhanced OCT to describe different morphological patterns of diabetic macular oedema and suggest that these indicate the severity of the disease. The cover photo comes from this paper. Fosmark and associates in Oslo demonstrate that levels of hydroimidazolone, an advanced glycation end product, in the vitreous are associated with diabetic retinopathy level. This may relate to blood–retinal barrier breakdown. Joussen et al. in Germany describe the design of a multicentre study to investigate the role of heavy silicone oils in proliferative vitreoretinopathy. The results of the clinical trial will be forthcoming in Acta in years to come. You and associates in China and Germany report from the Beijing Eye Study, where 0.7% of individuals have myelinated retinal nerve fibres and this has no clinical consequence. Minami et al. in Osaka study the effect of intraocular infusion pressure in vitreous surgery in rabbits. They suggest that ganglion cells may suffer from high intraocular pressure in this situation. Kjeka and associates in Bergen find photoptic ERG useful to predict neovascularization in patients with central retinal vein occlusion. Kirwan et al. in Dublin suggest that morphine analgesia may replace general anaesthesia in children who need laser treatment for retinopathy of prematurity. Vouri and Mäntyjärvi in Turku report for the first time that colour vision may be impaired in eyes with tilted optic discs. Delyfer et al. from Bordeaux contribute case reports on cytomegalovirus retinitis following intravitreal triamcinolone injections. Georgeopoulos et al. in Athens find capsular tension rings to be useful in eyes with traumatic zonular dialysis, which need cataract surgery. Wong et al. in Hong Kong find nylon and polyglactin sutures to be satisfactory in pterygium surgery. Caines and associates in Uppsala find that children with spina bifida have a high risk of stabismus, refractive error and subnormal vision. Muen et al. in Liverpool find periventricular leukomalacia in children who present with strabismus. Yazici and Akova from Turkey suggest that dacryocystorhinostomy may be performed bilaterally at the same time. In the Perspectives in Ophthalmlogy section, Sundling and associates in Norway survey Norwegian optometrists and report on their practice patterns, referrals and the disease prevalence of their patients. Kawana et al. in Japan use OCT to evaluate anterior chamber angle recession. Margolis et al. in Cleveland show a case with macular involvement resulting from breast cancer. I hope that each reader of Acta finds something of interest in this issue. You are invited to contribute letters to the editor regarding the subjects discussed in these articles.

Poly( N-isopropylacrylamide)–chitosan as thermosensitive in situ gel-forming system for ocular drug delivery

A novel copolymer, poly( N-isopropylacrylamide)–chitosan (PNIPAAm–CS), was investigated for its thermosensitive in situ gel-forming properties and potential utilization for ocular drug delivery. The thermal sensitivity and low critical solution temperature (LCST) were determined by the cloud point method. PNIPAAm–CS had a LCST of 32 °C, which is close to the surface temperature of the eye. The in vivo ocular pharmacokinetics of timolol maleate in PNIPAAm–CS solution were evaluated and compared to that in conventional eye drop solution by using rabbits according to the microdialysis method. The C max of timolol maleate in aqueous fluid for the PNIPAAm–CS solution was 11.2 μg/ml, which is two-fold higher than that of the conventional eye drop, along with greater AUC. Furthermore, the PNIPAAm–CS gel-forming solution of timolol maleate had a stronger capacity to reduce the intra-ocular pressure (IOP) than that of the conventional eye drop of same concentration over a period of 12 h. In addition, the MTT assay showed that there is little cytotoxicity of PNIPAAm–CS at concentration range of 0.5–400 μg/ml. These results suggest that PNIPAAm–CS is a potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bio-availability, efficacy, and compliance of some eye drugs.

Sustained Ocular Drug Delivery from a Temperature and pH Triggered Novel In Situ Gel System

Various ocular diseases like glaucoma, conjunctivitis, and dry eye syndrome require frequent drug administration. Poor ocular bioavailability of drugs (< 1%) from conventional eye drops is due mainly to the precorneal loss factors that include rapid tear turnover, nonproductive absorption, transient residence time in the cul-de-sac, and the relative impermeability of the drugs to corneal epithelial membrane. These problems may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac. Our present work describes the formulation and evaluation of an ocular delivery system of timolol maleate based on the concept of both temperature and pH-triggered in situ gelation. Pluronic F-127 (a thermosensitive polymer) in combination with chitosan (pH-sensitive polymer also acts as permeation enhancer) was used as gelling agent. The developed formulation was characterized for various in vitro parameters e.g., clarity, gelation temperature and pH, isotonicity, sterility, rheological behavior, drug release profile, transcorneal permeation profile, and ocular irritation. Developed formulation was clear, isotonic solution, that converted into gel at temperatures above 35°C and pH 6.9–7.0. A significant higher drug transport across corneal membrane and increased ocular retention time was observed using the developed formulation. The developed system is a viable alternative to conventional eye drops for the treatment of glaucoma and various other ocular diseases.

Study on the Ocular Pharmacokinetics of Ion-Activated In Situ Gelling Ophthalmic Delivery System for Gatifloxacin by Microdialysis

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of the drug may be overcome by the use of gel system. The present work was conducted to evaluate the relative bioavailability of ion-activated in situ ophthalmic gel of gatifloxacin by microdialysis. The conventional ophthalmic solution of gatifloxacin was used as reference. The AUC of test group is 3.8-fold vs. the reference group (1.4316 ± 0.1327 μg·mL−1·h vs. 0.3756 ± 0.0380 μg·mL−1·hr) (P < 0.05), and the Cmax of test group vs. the control group is 3.0-fold (0.3363 ± 0.0634 μg·mL−1 vs. 0.1112 ± 0.0151 μg·mL−1) (P < 0.05). The Tmax of test group is longer than that of reference group (2.0 ± 0.67 hr vs. 0.667 ± 0.17 hr) (P < 0.1), and Ke of test group is lower than that of reference group. The developed formulation has a higher bioavailability and longer residence time in aqueous humor than conventional ophthalmic solutions. The developed system is a viable alternative to conventional eye drops.

Microparticle systems based on polymer-drug interaction for ocular delivery of ciprofloxacin I. In vitro characterization

The interaction of polyelectrolytes with oppositely charged drugs can result in a reduction of polymer solubility and the formation of microparticles. Treating conjunctivitis with conventional eye drop formulations of ciprofloxacin (CPX) hydrochloride requires instillations at least three to four times a day. Patient compliance and drug efficacy can be significantly improved by increasing the residence time of the formulation in the conjunctival sac. This can be achieved by using a microparticle system, especially if coadministered with mucoadhesive polymers capable of interacting with both the formulation and the precorneal mucus. In this study, a microparticle system based on CPX and chondroitin sulphate (CS) was developed by slowly stirring aqueous solutions of CS into drug solutions. Ionic interaction between the drug and the oppositely-charged polymer resulted in a very fine precipitate (CPX/CS) from which the drug is released after the ions in the medium are displaced. The objective of this study was the in vitro characterization of CPX/CS microparticles, with particular attention to drug polymer interaction and particle size. The behavior of CPX/CS in a tear system model was assessed for comparison with a commercial eye drop solution. Mucoadhesive polymers such as carbomer, Na carboxymethylcellulose, gelatin and hydroxypropylcellulose were added to improve mucoadhesion. The effect of these polymers on drug release was also studied.

Ion-Activated, Gelrite®-Based in Situ Ophthalmic Gels of Pefloxacin Mesylate: Comparison with Conventional Eye Drops

The purpose of our work was to develop an ophthalmic delivery system of a flouroquinolone antibiotic, pefloxacin mesylate, based on the concept of ion-activated in situ gelation. Gelrite® gellan gum, a novel ophthalmic vehicle, that gels in the presence of mono- or divalent-cations present in the lacrimal fluid, was used as the gelling agent. The developed formulation was compared with marketed eye drops in efficacy of treatment of bacterial conjunctivitis that was induced artificially in rabbits. The formulations were evaluated for rheological characteristics, in vitro release behavior, antimicrobial efficacy, and efficacy against bacterial conjunctivitis.We found that in situ gelling formulations passed the test for sterility. The formulations exhibited a first-order release pattern over 12 hr in in vitro release studies. The developed formulation was effective against selected micro-organisms in antimicrobial efficacy studies. The shelf lives of formulation was >2 years. The formulation demonstrated better therapeutic efficacy compared with standard eye drops because it improved the clinical parameters monitored for prolonged periods. The developed formulations can be considered as a viable alternative to conventional eye drops.

Sustained ophthalmic delivery of gatifloxacin fromIn situgelling system

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid precorneal elimination of drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, gatifloxacin, based on the concept of ion-activated systems. Sodium alginate was used as the gelling agent in combination with hydroxy propyl methyl cellulose (Methocel E50LV), which acted as a viscosity enhancing agent. The developed formulations were therapeutically efficacious, stable, non-irritant and provided sustained release of the drug over an eight hour period. The developed system is thus a viable alternative to conventional eye drops.