Conventional Ophthalmic Solutions Research Articles

FORMULATION AND EVALUATION OF CETIRIZINE HYDROCHLORIDE pH TRIGGED IN-SITU OCULAR GEL

Objective: In the present research work, the aim was to prepare pH trigged in-situ ocular gel of Cetirizine Hydrochloride (CTZ) to improve its local bioavailability at the eye surface. Methods: CTZ in-situ ocular gel was prepared by the pH-trigged method. In-situ CTZ ocular gel was prepared by a pH-sensitive gelling agent (Carbomer) with a one-viscosity builder polymer (HPMC E4M). All formulation was evaluated for appearance, pH, viscosity at different pH, gelling capacity, % drug content, and drug release. Nine formulations were prepared and optimized successfully using 32 factorial designs. Optimization was done by DoE software version Version 13.0.10.064. Results: All nine formulations of in-situ ocular gel were subjected to evaluation. Out of 9 formulations, F3 had a good gelling capacity with the minimum amount of polymer. The appearance of the optimized formulation was translucent and homogenous. The pH of the F3 formulation is 5.55±0.07, which is good for maintaining formulation in the solution stage. Viscosity at 20 RPM of F3 formulation at pH 5.5 is 837.30±1.00 cps; this range of viscosity has good flow properties. Viscosity at 20 RPM of F3 formulation at pH 7.4 is 6800.74±1.58cps; this range of viscosity has a good gelling capacity which helps to drug retain at the eye surface. Drug content is 100.16±0.53%. Drug release at 300 min is 69.22±2.12, it can say that the drug may be retained for more than 300 min at the eye surface, which is good for reducing dosing frequency. Conclusion: CTZ was successfully formulated in pH triggered in-situ gelling system using Carbomer 974P in combination with HPMC E4M. The prepared in-situ gel is easily converted from solution stage to gel stage at the pH of the eye so we can say that the drug in the in-situ ocular gel is more bioavailable than conventional ophthalmic solution In vitro results indicated that the in-situ gel system is a viable alternative to conventional ocular drops by virtue of its ability to sustain drug release.

Formulation Development and Characterisation of Gemifloxacin Mesylate and Loteprednol Etabonate Ophthalmic Ocuserts

Gemifloxacin Mesylate is a fluoroquinolone antibacterial drug preferably used in the treatment of bacterial conjunctivitis. The addition of Loteprednol Etabonate enhances the anti-inflammatory activity of the developed formulation. The objective of the present work was to develop ocular inserts of Gemifloxacin Mesylate with Loteprednol Etabonate and thereby evaluate its potential as a sustained ocular delivery system. Poor bioavailability and poor therapeutic responses are associated with conventional ophthalmic solutions due to many pre-corneal constraints. These constrain trigger the researcher's mind to formulate a controlled and sustained drug delivery system. Ocular inserts based on the solvent cast technique were formulated and characterized by in vitro drug release studies using a flow-through apparatus that simulated the eye conditions. Compatibility of Gemifloxacin Mesylate, Loteprednol Etabonate, polymer, and excipients was checked based on preformulation studies. Different combinations of Gemifloxacin Mesylate, Loteprednol Etabonate, Carbopol 974, 98 981, PEG 400, and glycerine were formulated by the solvent cast method and evaluated. Clarity, smoothness, surface pH, drug content, and in-vitro drug release study were the various parameters evaluated on the formulated ocusert. Formula GLE 74 fulfilled the needs of all organoleptic parameters and also the in-vitro release study. Based on in vitro correlation stability studies, it was concluded that this ocular inserts formulation could be a promising controlled release formulation.

The use of sea water as a homemade remedy for infectious conjunctivitis-any cause for alarm?

Abstract Aim This study sought to ascertain the usefulness of sea water (SW) in the treatment of infectious conjunctivitis as a homemade medicine. Methods The SW was collected at the sea shore (Gulf of Guinea) in Cape Coast, into a sterile container and kept at 4 °C. This was prepared into different concentrations for assaying in comparison to Normal Saline (NS) and Autoclaved Sea water (AS) which was prepared in the laboratory. The pH, ionic concentration and salinity of SW and NS were determined prior to the antimicrobial assay. Conventional ophthalmic solutions of Chloramphenicol (CH) Gentamycin (Gen), Ciprofloxacin (Cipro) and Tobramycin (Tobra) were used as standards for comparison. The antibacterial susceptibility test was performed against the strains of Staphylococcus spp, Bacillus. spp, Corynebacterium spp, Pseudomonas spp, Haemophilus spp and Klebseilla spp. isolated from clinical cases of infectious conjunctivitis. Minimum inhibition concentrations (MIC) and minimum bactericidal concentration (MBC) were determined for all test agents. Results AS, NS and CH showed bacteriostatic activity against all gram positive bacteria with MIC values of 350–560 µg/mL, 36,000 µg/mL and 5000 µg/mL respectively. NS did the same against only Pseudomonas spp. All Gen, Cipro and Tobra revealed bactericidal activity against all bacteria with MIC and (MBC) value of 3000 µg/mL. However, SW showed no antimicrobial effect but rather introduced other additional bacteria upon subculturing. Conclusion The use of SW as a homemade therapy for infectious conjunctivitis is a risky practice, however, when autoclaved could be beneficial against Gram positive bacteria. Alternatively, normal saline could serve the purpose of first aid homemade therapy for infectious conjunctivitis.

Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel

Context: Conventional ophthalmic solutions often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of drug in the pre-corneal area.Objectives: Above problem can be overcome by the use of in situ gel forming systems that are instilled as drops in to the eye and undergo a sol–gel transition in the cul-de-sac.Methods: An ion sensitive polymer gellan gum was used as gelling agent which formed immediate gel and remained for extended time period. Nanoparticles of moxifloxacin, prepared by solvent evaporation, were separated by freeze drying. The rheological properties and in vitro drug release test of in situ gel loaded with nanoparticles were evaluated and compared with marketed preparation. In vitro release study demonstrated diffusion controlled release for moxifloxacin from formulations over a period of 12 h.Results: The developed formulation was stable and showed enhanced contact time minimizing the frequency of administration. Confocal microscopy showed clear permeation of drug loaded nanoparticles across L/S of cornea.Conclusion: The formulation of moxifloxacin was found liquid at the formulated pH and formed gel in the presence of mono or divalent cations. The gel formed in situ showed sustained drug release over a period of 10–12 h. The formulations were less viscous before instillation and formed strong gel after instilling it into cul-de-sac. It is thus concluded that by adopting a systematic formulation approach, an optimum point can be reached in the shortest time with minimum efforts to achieve desirable rheological and in vitro release property for in situ gel forming system.

Evaluation of gatifloxacin pluronic micelles and development of its formulation for ocular delivery.

The purpose of the present study was to enhance the solubility of gatifloxacin by developing self-assembling pluronic micelles of gatifloxacin for ocular delivery, to overcome the problem of poor bioavailability and therefore lesser therapeutic response exhibited by conventional ophthalmic solutions of the drug. Gatifloxacin was loaded in micelles by solid dispersion method using Pluronic F127 and evaluated for particle size, drug loading, loading efficiency, in vitro transcorneal permeation study, in vitro drug release, solubility studies, microbiological studies, ex vivo mucoadhesive strength, and ocular safety studies. The drug loading and drug loading efficiency studies revealed that gatifloxacin/Pluronic F127 ratio of 0.25/2.52g offered good drug loading (9.96%), high loading efficiency (90%), and acceptable particle size of 176nm (polydispersity index 0.345). Hen's egg test chorioallantoic membrane (HET-CAM) assay with 0 score in 8h and ocular safety test with score of 2 indicate the nonirritant property of the developed pluronic micelles. In vitro transcorneal permeation studies through excised goat cornea indicated increase in ocular availability with no corneal damage. In vitro drug release data of optimized formulation provided sustained release over a period of 8h. Optimized formulation was found to possess acceptable transcorneal permeation and antimicrobial efficacy when compared to marketed eye drops. The solubility studies of gatifloxacin from these lyophilized pluronic micelles revealed 18.67-fold increase in comparison to gatifloxacin suspension in water. The pluronic micelles could enhance ocular bioavailability of gatifloxacin, prolong its residence time in the eyes, and may lead to reduced instillation frequency, thereby resulting in better patient compliance.

Comparison of systemic absorption between ofloxacin ophthalmic in situ gels and ofloxacin conventional ophthalmic solutions administration to rabbit eyes by HPLC–MS/MS

In recent years, many pharmaceutical scientists have focused on developing the in situ gel-forming systems to overcome the poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug. The present work was to compare the systemic absorptions of ophthalmic ofloxacin in situ gel with the conventional ofloxacin eye drop after topical instillation to rabbit eyes by HPLC-MS/MS method and also determine the relative contribution of the nasal and the conjunctival mucosae to systemic ofloxacin absorption following topical instillation. The systemic AUC, Cmax, Tmax and Ke for ophthalmic in situ gel and ophthalmic solution after ocular instillation were 202.63±118.85 and 202.25±57.74 ng mL(-1) h, 54.22±28.31 and 48.4±25.97 ng mL(-1), 1.08±0.20 and 1.25±0.88 h, 0.0576±0.0207 and 0.0388±0.0248, respectively. And the values for the ratios of the AUC of anterior chamber of rabbit eye to blood plasma, AUCac/AUCpl, for ofloxacin conventional eye drop and in situ gel were 0.25 and 0.52, respectively. Statistic results showed that there was no significant difference in systemic absorption between the test groups and the reference groups (P>0.05) as both formulations have an AUCsa/AUCpl of 0.35. Therefore, the ophthalmic in situ gel may not decrease the drugs systemic absorption when administered in an equivalent dose as ophthalmic solutions into the rabbit eyes.

Controlled ocular drug delivery of ofloxacin using temperature modulated in situ gelling system

Background: The designing of ocular dosage form off ers complicated issues. Numerous protective mechanisms are present in the eye to prevent the absorption of drug candidate from the corneal membrane. 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 in situ gel forming systems, which are instilled as drops into the eye and then undergo a sol-gel transition in the cul-de-sac. In situ forming polymeric formulations drug delivery systems is in sol form before administration in the body, but once administered, undergoes gelation in situ to form a gel. The formulation of gel depends upon factors like temperature modulation, pH changes, presence of ions, and ultraviolet irradiation, from which drug gets released in sustained and controlled manner. Objective: The present investigation deals with formulation and evaluation of Pluronic; based in situ gel of ofloxacin. Material and Method: Pluronic as gelling agent, HPMC as viscosity modifying agent was used. Ofloxacin was used as Active Pharmaceutical Ingredient. Results: In vitro drug release studies indicated that the formulated in situ gel retained the drug better than the conventional dosage forms. The formulations were therapeutically efficacious, sterile, stable, and provided controlled release of the drug over a period of time. Conclusion: The results demonstrate that the developed system is an alternative to conventional ophthalmic drops, patient compliance, industrially-oriented, and economical.

DESIGN AND CHARACTERIZATION OF SUSTAINED RELEASE LEVOFLOXACIN OCULAR INSERTS

Levofloxacin is a fluoroquinolone antibacterial drug effective in the treatment of bacterial conjunctivitis. The objective of the present work was to develop ocular inserts of levofloxacin and evaluate their potential for sustained ocular delivery. Conventional ophthalmic solution shows the poor bioavailability and therapeutic response due t many pre-corneal constraints. These constrains necessitates the controlled and sustained drug delivery to become standard one in modern pharmaceutical era Matrix type ocular inserts were prepared by the film casting technique in Teflon coated Petri dishes and characterized in vitro by drug release studies using a flow through apparatus that simulated the eye conditions. Nine formulations were developed, which differed in the ratio of polymers - chitoson, polyvinyl alcohol (PVA). All the formulations were subjected to evaluation of thickness, weight variation, folding endurance, drug content uniformity, in vitro release study, Surface pH, Swelling Studies (Swelling Index), % Moisture absorption, Release Kinetics, and Ocular Irritation Studies. On the basis of in vitro drug release studies, the formulation L9 was found to be better than the other formulations and it was selected as an optimized formulation.

Design and evaluation of thermoreversible in situ gelling system of forskolin for the treatment of glaucoma

The contact time of a vehicle on the cornea is of utmost importance for ophthalmic drug delivery. The poor bioavailability and therefore poor therapeutic response exhibited by the conventional ophthalmic solutions due to pre-corneal elimination of a drug may be overcome by the use of the in situ gel forming systems, which upon instillation as drops into the eye, undergo a sol-gel transition in the cul-de-sac. The purpose of this work was to develop an ophthalmic delivery system of the forskolin, based on the concept of temperature activated in situ gelation. Poloxamer 407 (Pluronic F-127) is a block copolymer made of poly (oxy ethylene) and poly (oxy propylene). The sol-gel transition is induced by an increase in temperature; however, it depends on the concentration of the polymer and presence of other additives. The developed formulations were therapeutically efficacious (on albino New Zealand rabbit model); reducing intra ocular pressure (IOP) for 12 hours and showed sol-gel phase transition (gelling) temperature of 22°C and sustained drug release 72% ± 0.056% in vitro behavior over a period of 4 h.

Effect of salts on gelation and drug release profiles of methylcellulose-based ophthalmic thermo-reversible in situ gels

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of thermo-reversible in situ gel. The purpose of this study was to examine the influence of different salts on the gelation, rheology and drug release of in situ gel based on methylcellulose. The gel temperature of 1% w/v methylcellulose (MC) was 60°C. It was found that 5–7% w/v sodium chloride (NaCl), 8–9% w/v potassium chloride (KCl), or 5% w/v sodium bicarbonate (NaHCO3) was capable of decreasing the gel temperature below physiological temperature, i.e. 37°C. Rheological studies indicated a large increase in viscosity at 37°C with the addition of salts in MC solutions. The duration of drug release from MC solution was 1.5 h. The significant observation was that the duration of drug release increased from 1.5 h to 3–5 h from salted MC solutions depending on the concentration and the type of salt. So, it can be concluded that the salted MC solutions were a better alternative than the MC solution to enhance the ocular bioavailability of the drug.

Drug delivery to eye: Special reference to nanoparticle.

Controlled and sustained delivery of ophthalmic drugs continues to remain a major focus area in the field of pharmaceutical drug delivery with the emergence of new, more potent drugs and biological response modifiers that may also have very short biological half-lives. The major objective of clinical therapeutics is to provide and maintain adequate concentration of drugs at the site of action. In ocular drug delivery, the physiological constraints imposed by the protective mechanisms of the eye lead to poor absorption of drugs with very small fractions of the instilled dose penetrating the cornea and reaching the intraocular tissues. The anatomy, physiology, and biochemistry of the eye render this organ highly impervious to foreign substances. A significant challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage. Development of newer, more sensitive diagnostic techniques and novel therapeutic agents continue to provide ocular delivery systems with high therapeutic efficacy. Conventional ophthalmic solution, suspension, and ointment dosage forms no longer constitute optimal therapy for these indications. Nanoparticles and nanosuspensions are showing a better application as compare to conventional delivery sysyems. Polymer nanoparticles proposed are reported to be devoid of any irritant effect on cornea, iris, and conjunctiva and thus appear to be a suitable inert carrier for ophthalmic drug delivery. The benefits of having the drug in the form of a nanoparticulate suspension are: reduction in the amount of dose, drug release for a prolonged period of time, higher drug concentrations in the infected tissue, longer residence time of nanoparticles on the cornea surface, reduction systemic toxicity of drug. Keywords: Nanoparticle; polymer; ocular; bioavailability

Once a day ocular inserts for sustained delivery of levofloxacin: Design, formulation and evaluation

Levofloxacin is a fluoroquinolone antibacterial drug effective in the treatment of bacterial conjunctivitis.The objective of the present work was to develop ocular inserts of levofloxacin and evaluate their potential for sustained ocular delivery. Conventional ophthalmic solution shows the poor bioavailability and therapeutic response due to many pre-corneal constraints. These constrains necessitate the controlled and sustained drug delivery to become a standard one in the modern pharmaceutical era. Matrix-type ocular inserts were prepared by the film-casting technique in Teflon-coated Petri dishes and characterized in vitro by drug release studies using a flow-through apparatus that simulated the eye conditions. Nine formulations were developed, which differed in the ratio of polymers polyethylene oxide (PEO), hydroxypropyl cellulose (HPC) and ethyl cellulose (EC). All the formulations were subjected to evaluation of thickness, weight variation, folding endurance and drug content uniformity and in vitro release study. On the basis of in vitro drug release studies, the formulation with PEO/EC (F9) was found to be better than the other formulations (release of 101.35% within 24 hrs) and it was selected as an optimized formulation, which was further subjected to in vivo studies and ageing studies. The in vitro result revealed that formulation F9 followed a perfect zero-order kinetics release (n 5 1.03) and the rest of the formulations released the drug by super case II kinetics (n . 1). It was also observed that increasing the proportion of PEO and HPC to EC increases the rate of release of Levofloxacin. On the basis of in vitro and in vivo correlation stability studies, it can be concluded that this ocular inserts formulation can be a promising once-a-day controlled release formulation.

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.

Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin

Conventional ophthalmic solutions often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of the drug in the precorneal area. To solve these problems, we developed a thermosensitive in situ gelling and mucoadhesive ophthalmic drug delivery system containing puerarin based on poloxamer analogs (21% (w/v) poloxamer 407/5% (w/v) poloxamer 188) and carbopol (0.1% (w/v) or 0.2% (w/v) carbopol 1342P NF). The combined solutions would convert to firm gels under physiological condition and attach to the ocular mucosal surface for a relative long time. The incorporation of carbopol 1342P NF not only did not affect the pseudoplastic behavior with hysteresis of the poloxamer analogs solution and leaded to a higher shear stress at each shear rate, but also enhanced the mucoadhesive force significantly. In vitro release studies demonstrated diffusion-controlled release of puerarin from the combined solutions over a period of 8 h. In vivo evaluation (the elimination of puerarin in tear and intraocular pressure-lowering effect) indicated the combined solutions had better ability to retain drug than poloxamer analogs or carbopol alone. It appears that ocular bioavailability can be increased more readily by using the in situ gelling and mucoadhesive vehicle.

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.

Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and then 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 in situ gelation. Alginate (Kelton ®) was used as the gelling agent in combination with HPMC (Methocel E50Lv) which acted as a viscosity-enhancing agent. The rheological behaviors of all formulations were not affected by the incorporation of gatifloxacin. Both in vitro release studies and in vivo pre-corneal retention studies indicated that the alginate/HPMC solution retained the drug better than the alginate or HPMC E50Lv solutions alone. These results demonstrate that the alginate/HPMC mixture can be used as an in situ gelling vehicle to enhance ocular bioavailability and patient compliance.

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.

Preparation and Evaluation of Sustained Ophthalmic Gel of Enoxacin

ABSTRACTThe 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 a gel system. The present work describes the formulation and evaluation of an ophthalmic delivery system containing an antibacterial agent, enoxacin, based on the concept of ophthalmic sustained gel, in which 2-hydroxypropyl-beta-cyclo-dextrin (HP-β-CD) was used as a penetration enhancer in combination with hydroxypropylmethylcellulose (Methocel F4M) which acted as a vehicle. The developed formulation was therapeutically efficacious, nonirritant, and provided sustained release of the drug over 8 h period in vitro and 7 h period in vivo. The developed system is a viable alternative to conventional eye drops.

Age and Sex Differences in Meibomian Gland Lipids

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and then 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 in situ gelation. Alginate (Kelton®) was used as the gelling agent in combination with HPMC (Methocel E50Lv) which acted as a viscosity-enhancing agent. The rheological behaviors of all formulations were not affected by the incorporation of gatifloxacin. Both in vitro release studies and in vivo pre-corneal retention studies indicated that the alginate/HPMC solution retained the drug better than the alginate or HPMC E50Lv solutions alone. These results demonstrate that the alginate/HPMC mixture can be used as an in situ gelling vehicle to enhance ocular bioavailability and patient compliance.

Ion-Activated In Situ Gelling Systems for Sustained Ophthalmic Delivery of Ciprofloxacin Hydrochloride

The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the 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. Our present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, CPH, 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 alone and in combinations with sodium alginate as the gelling agent. The developed formulations were therapeutically efficacious and provided sustained release of the drug over an 8-hr period in vitro.