Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drops through excised goat, sheep, and buffalo corneas

The purpose of this investigation was to evaluate the effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drop through freshly excised goat, sheep, and buffalo corneas. Aqueous isotonic ophthalmic solutions of moxifloxacin hydrochloride of different concentrations (pH 7.2) or 0.5% (wt/vol) solutions of different pH or 0.5% solutions (pH 7.2) containing different preservatives were made. Permeation characteristics of drug were evaluated by putting 1 mL formulation on freshly excised cornea (0.50 cm²) fixed between donor and receptor compartments of an all-glass modified Franz diffusion cell and measuring the drug permeated in the receptor (containing 10 mL bicarbonate ringer at 37°C under stirring) by spectrophotometry at 291 nm, after 120 minutes. Statistical analysis was done by one-way analysis of variance (ANOVA) followed by Dunnett’s test. Increase in drug concentration in the formulation resulted in an increase in the quantity permeated but a decrease in percentage permeation. Increase in pH of the solution from 5.5 to 7.2 increased drug permeation, indicating pH-dependent transport. Compared with control formulation, moxifloxacin 0.5% (wt/vol) solution (pH 7.2) containing disodium edetate (EDTA) (0.01% wt/vol) produced significantly (P<.05) higher permeation with all the corneas. Formulation with benzyl alcohol significantly (P<.05) increased permeation with buffalo cornea compared with its control. Presence of benzalkonium chloride (BAK) (0.01% wt/vol) and EDTA (0.01% wt/vol) in the formulation increased permeation to the maximum with all the corneas. The results suggest that moxifloxacin 0.5% ophthalmic solution (pH 7.2) containing BAK (0.01%) and EDTA (0.01%) provides increased in vitro ocular availability through goat, sheep, and buffalo corneas. Published: February 10, 2006 Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi-110017, India     

Effect of preservative,antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine

The influence of formulation additives, e.g. preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine from 0.5%(w/v) aqueous drop was studied using goat cornea. Permeation characteristics of drug, from selected formulations, through excised rabbit cornea were also evaluated. Aqueous solution of ketorolac tromethamine (0.5% w/v), pH 6.5 or 7.0 having ionic strength 0.2, was prepared. To this solution perservatives either alone or in combination with other additives were added to have drops of various composition. Permeation studies with goat cornea showed maximum permeation of ketorolac tromethamine from formulation containing benzalkonium chloride and disodium edetate. Increase in viscosity of drop resulted in decreased permeation of drug. Formulation containing benzalkonium chloride and disodium edetate also increased permeation of drug through rabbit cornea. Cumulative permeation of drug through rabbit cornea was found to be 2.3-2.4 fold higher than that observed with goat cornea.     

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®.     

Permeation through cornea

The permeability of the cornea to drugs is clinically important because it is the major factor determining the efficacy of topically applied ophthalmic preparations. With this perspective, the present article gives a brief update and overview of corneal structure and proposed mechanisms of permeation. Physiological, physicochemical and formulation factors affecting drug permeation through cornea are highlighted. Influence of ocular penetration enhancers on drug permeation is also discussed.     

Thiolated pectin nanoparticles: Preparation, characterization and ex vivo corneal permeation study

The objective of present study was to prepare thiolated pectin nanoparticles and to evaluate them for ocular delivery. Thiolated pectin nanoparticles were prepared by ionotropic-gelation technique using magnesium chloride as the ionic cross-linker and timolol maleate as the model drug. The results revealed that increasing the concentration of magnesium chloride results in significant increase in particle size, while % entrapment is decreased significantly by increase in the concentration of thiolated pectin. The optimal formulation having particle size of 237 nm and % entrapment of 94.6% was obtained at concentrations of thiolated pectin - 0.01% (w/v) and magnesium chloride - 0.01% (w/v). On comparative evaluation, thiolated pectin nanoparticulate formulation provided significantly higher ex vivo corneal permeation of timolol maleate across the excised goat cornea than the conventional aqueous solution.     

Carboxymethyl tamarind kernel polysaccharide nanoparticles for ophthalmic drug delivery

Tropicamide-loaded carboxymethyl tamarind kernel polysaccharide (CMTKP) nanoparticles were prepared and evaluated for ocular delivery. Preparation of ionotropically gelled CMTKP nanoparticles was optimized employing three-levels, two-factor central composite design. Concentration of polymer and crosslinker had significant synergistic effect on particle size and % encapsulation efficiency. The optimal calculated parameters were concentrations of CMTKP 0.10% (w/v) and calcium chloride 0.11% (w/v). The optimized tropicamide-loaded CMTKP formulation showed ex vivo corneal permeation of tropicamide across isolated goat cornea comparable to its aqueous solution. Further, the mucoadhesive and non-irritant nature of CMTKP nanoparticles indicate their suitability as ocular delivery system.     

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU. Published: February 16, 2007     

In vivo ocular availability of ketorolac following ocular instillations of aqueous,oil, and ointment formulations to normal corneas of rabbits: A technical note

Conclusions  In vivo ocular availability of ketorolac was evaluated following ocular instillation of aqueous, oil, and ointment formulations to normal corneas of rabbits and monitoring ketorolac concentration in aqueous humor by HPLC. Compared with aqueous drop, sesame and soybean oil drops of ketorolac provided higher ocular availability followed by ophthalmic ointment. The ointment formulation provided maximum sustained effect. Ketorolac aqueous drop with BAC and EDTA improved the rate of ocular absorption though not the extent. Published: October 24, 2005     

Mucoadhesive bilayer tablets of propranolol hydrochloride

The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5∶1 (F2) had the maximum percentage of in vitro drug release without disinte-gration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satis-factory (7.0±1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good biodhesive strength (28.9±0.99 g) and sustained in vitro drug permeation (68.65%±3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration. Published: September 21, 2007     

Nanoemulsion based gel for transdermal delivery of meloxicam: Physico-chemical,mechanistic investigation

AimsThe aim of the present investigation was to develop a nanoemulsion (NE) gel formulation for the transdermal delivery of meloxicam (MLX) in order to ensure maximum controlled and sustained drug release capacity.Main methodsThe MLX containing NE gel was prepared and characterized for particle size, zeta potential, pH, rheology, in vitro drug release, in vitro skin permeation, and in vitro hemolysis. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) of MLX-NE gel treated rat skin was performed to investigate the skin permeation mechanism of meloxicam from NE gel. Skin permeation potential of the developed gel formulation was assessed using confocal laser scanning microscopy (CLSM). The in vivo toxicity of MLX-NE gel was assessed by histopathological examination in rat. The rat paw edema test was performed to evaluate the anti-inflammatory activity of MLX-NE gel.Key findingsPercutaneous absorption studies demonstrated a higher permeation of meloxicam from NE gel, than the drug solution. FTIR and DSC studies supported stratum corneum lipid extraction as a possible penetration enhancer mechanism for MLX-NE gel. CLSM studies confirmed the permeation of the NE gel formulation to the deeper layers of the skin (up to 130 μm). MLX-NE gel turned out to be non-irritant, biocompatible, and provided maximum inhibition of paw edema in rats over 24 h in contrast to MLX solution.SignificanceThe nanoemulsion gel formulation may hold promise as an effective alternative for the transdermal delivery of meloxicam.     

Feasibility of transdermal delivery of fluoxetine

Feasibility of developing a transdermal drug delivery of fluoxetine has been investigated. Permeation studies of fluoxetine across human cadaver skin were carried out using Franz diffusion cells. The receptor phase consisted of pH 7.4 phosphate buffer maintained at 37°C. Permeation enhancement of fluoxetine, either in the salt or base form, was achieved using various enhancers like azone, SR-38, and ethanol. Various O/W microemulsion systems of fluoxetine were developed to study their effect on the skin permeation of fluoxetine. The results indicated that ethanol at 65% vol/vol was able to increase the permeation of fluoxetine the most, while microemulsion systems showed decrease in the permeation of fluoxetine. The permeation of fluoxetine obtained using a 65% vol/vol ethanolic solution was found to be sufficient to deliver the required dose (20–80 mg) from a patch of feasible size. The results seem promising for developing a transdermal drug delivery system of fluoxetine. Published: September 30, 2005     

Preparation and Evaluation of Thermosensitive Liposomal Hydrogel for Enhanced Transcorneal Permeation of Ofloxacin

Ofloxacin, available as ophthalmic solution, has two major problems: first, it needs frequent administration every 4 hours or even every 1 hour to treat severe eye infection; second, there is formation of white crystalline deposit on cornea due to its pH-dependent solubility, which is very low at pH of corneal fluid. In order to provide a solution to previous problems, ofloxacin in this study is prepared as topically effective in situ thermosensitive prolonged release liposomal hydrogel. Two preparation procedures were carried out, leading to the formation of multilamellar vesicles (MLVs) and reverse-phase evaporation vesicles (REVs) at pH 7.4. Effects of method of preparation, lipid content, and charge inducers on encapsulation efficiency were studied. For the preparation of in situ thermosensitive hydrogel, chitosan/β-glycerophosphate system was synthesized and used as carrier for ofloxacin liposomes. The effect of addition of liposomes on gelation temperature, gelation time, and rheological behaviors of the hydrogel were evaluated. In vitro transcorneal permeation was also determined. MLVs entrapped greater amount of ofloxacin than REVs liposomes at pH 7.4; drug loading was increased by including charge-inducing agent and by increasing cholesterol content until a certain limit. The gelation time was decreased by the addition of liposomes into the hydrogel. The prepared liposomal hydrogel enhances the transcorneal permeation sevenfold more than the aqueous solution. These results suggested that the in situ thermosensitive ofloxacin liposomal hydrogel ensures steady and prolonged transcorneal permeation, which improves the ocular bioavailability, minimizes the need for frequent administration, and decreases the ocular side effect of ofloxacin.     

Ciprofloxacin as Ocular Liposomal Hydrogel

The purpose of this study was to prepare and characterize an ocular effective prolonged-release liposomal hydrogel formulation containing ciprofloxacin. Reverse-phase evaporation was used for preparation of liposomes consisting of soybean phosphatidylcholine (PC) and cholesterol (CH). The effect of PC/CH molar ratio on the percentage drug encapsulation was investigated. The effect of additives such as stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively, were studied. Morphology, mean size, encapsulation efficiency, and in vitro release of ciprofloxacin from liposomes were evaluated. For hydrogel preparation, Carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency of 73.04 ± 3.06% was obtained from liposomes formulated with PC/CH at molar ratio of 5:3 and by increasing CH content above this limit, the encapsulation decreased. Positively charged liposomes showed superior entrapment efficiency (82.01 ± 0.52) over the negatively charged and the neutral liposomes. Hydrogel containing liposomes with lipid content PC, CH, and SA in molar ratio 5:3:1, respectively, showed the best release and transcorneal permeation with the percentage permeation of 30.6%. These results suggest that the degree of encapsulation of ciprofloxacin into liposomes and prolonged in vitro release depend on composition of the vesicles. In addition, the polymer hydrogel used in preparation ensure steady and prolonged transcorneal permeation. In conclusion, ciprofloxacin liposomal hydrogel is a suitable delivery system for improving the ocular bioavailability of ciprofloxacin.     

Nanoemulsions as vehicles for transdermal delivery of aceclofenac

The aim of the present study was to investigate the potential of a nanoemulsion formulation for transdermal delivery of aceclofenac. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudoternary phase diagrams. The prepared nanoemulsions were subjected to different thermodynamic stability tests. The nanoemulsion formulations that passed thermodynamic stability tests were characterized for viscosity, droplet size, transmission electron microscopy, and refractive index. Transdermal permeation of aceclofenac through rat abdominal skin was determined by Franz diffusion cell. The in vitro skin permeation profile of optimized formulations was compared with that of aceclofenac conventional gel and nanoemulsion gel. A significant increase in permeability parameters such as steady-state flux (J(ss)), permeability coefficient (K(p)), and enhancement ratio (E(r)) was observed in optimized nanoemulsion formulation F1, which consisted of 2% wt/wt of aceclofenac, 10% wt/wt of Labrafil, 5% wt/wt of Triacetin, 35.33% wt/wt of Tween 80, 17.66% wt/wt of Transcutol P, and 32% wt/wt of distilled water. The anti-inflammatory effects of formulation F1 showed a significant increase (P < .05) in percent inhibition value after 24 hours when compared with aceclofenac conventional gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of aceclofenac.     

Use of Fish Scale-Derived BioCornea to Seal Full-Thickness Corneal Perforations in Pig Models

The aim of this study was to test the use of BioCornea, a fish scale-derived collagen matrix for sealing full-thickness corneal perforations in mini-pigs.Two series of experiments were carried out in 8 Lan-Yu and 3 Göttingen mini-pigs, respectively. A 2mm central full thickness corneal perforation was made with surgical scissors and 2mm trephines. The perforations were sealed immediately by suturing BioCornea to the wounded cornea. The conditions of each patched cornea were followed-up daily for 3 or 4 days. Status of operated eyes was assessed with slit lamp examination or optical coherence tomography (OCT). Animals were sacrificed after the study period and the corneas operated were fixated for histological examination.Both OCT imaging and handheld slit lamp observations indicated that a stable ocular integrity of the perforated corneas was maintained, showing no leakage of aqueous humor, normal depth of anterior chamber and only mild swelling of the wounded cornea. Hematoxylin and eosin staining of the patched cornea showed no epithelial ingrowths to the perforated wounds and no severe leucocyte infiltration of the stroma.The fish scale-derived BioCornea is capable to seal full-thickness corneal perforation and stabilize the integrity of ocular anterior chamber in pre-clinic mini-pig models. BioCornea seems to be a safe and effective alternative for emergency treatment of corneal perforations.     

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.     

Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets

The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating tablet (RDT) of the taste-maske drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8∶2 did not show drug release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1∶1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t₉₀, 60 seconds) in SGF compared with marketed formulation (t₉₀, 240 seconds;P<.01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity. Published: June 22, 2007     

Once-daily sustained-release matrix tablets of nicorandil: Formulation and in vitro evaluation

The objective of the present study was to develop once-daily sustained-release matrix tablets of nicorandil, a novel potassium channel opener used in cardiovascular diseases. The tablets were prepared by the wet granulation method. Ethanolic solutions of ethylcellulose (EC), Eudragit RL-100, Eudragit RS-100, and polyvinylpyrrolidone were used as granulating agents along with hydrophilic matrix materials like hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, and sodium alginate. The granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, and in vitro release studies. The granules showed satisfactory flow properties, compressibility, and drug content. All the tablet formulations showed acceptable pharmacotechnical properties and complied with in-house specifications for tested parameters. According to the theoretical release profile calculation, a oncedaily sustained-release formulation should release 5.92 mg of nicorandil in 1 hour, like conventional tablets, and 3.21 mg per hour up to 24 hours. The results of dissolution studies indicated that formulation F-I (drug-to-HPMC, 1∶4; ethanol as granulating agent) could extend the drug release up to 24 hours. In the further formulation development process, F-IX (drug-to-HPMC, 1∶4; EC 4% wt/vol as granulating agent), the most successful formulation of the study, exhibited satisfactory drug release in the initial hours, and the total release pattern was very close to the theoretical release profile. All the formulations (except F-IX) exhibited diffusion-dominated drug release. The mechanism of drug release from F-IX was diffusion coupled with erosion.     

Preparation and evaluation of chitosan/carrageenan beads for controlled release of sodium diclofenac

The polyelectrolyte complex (PEC) hydrogel beads based on chitosan (CS) and carrageenan (CR) have been studied as a controlled release device to deliver sodium diclofenac (DFNa) in the simulated gastrointestinal condition. Various factors potentially influencing the drug release (ie, CS/CR proportion, DFNa content, types and amount of cross-linking agents) were also investigated. The optimal formulation was obtained with CS/CR proportion of 2/1 and 5% (wt/vol) DFNa. The controlled release of the drug from this formulation was superior to other formulations and was able to maintain the release for approximately 8 hours. Upon cross-linking with glutaric acid and glutaraldehyde, the resulting beads were found to be more efficient for prolonged drug release than their non-cross-linking counterparts. The bead cross-linked with glutaraldehyde was able to control the release of the drug over 24 hours. The difference in the drug release behavior can be attributed to the differences in ionic interaction between the oppositely charged ions and to the concentrations of the drug within the beads, which depends on the compositions of the formulation and the pH of the dissolution medium. The release of drug was controlled by the mechanism of the dissolution of DFNa in the dissolution medium and the diffusion of DFNa through the hydrogel beads.     

Development of Timolol-Loaded Galactosylated Chitosan Nanoparticles and Evaluation of Their Potential for Ocular Drug Delivery

This study was conducted to develop timolol maleate (TM)-loaded galactosylated chitosan (GC) nanoparticles (NPs) (TM-GC-NPs) followed by optimization via a four-level and three-factor Box–Behnken statistical experimental design. The optimized nanoparticles showed a particle size of 213.3?±?6.83 nm with entrapment efficiency of 38.58?±?1.31% and drug loading of 17.72?±?0.28%. The NPs were characterized with respect to zeta potential, pH, surface morphology, and differential scanning calorimetry (DSC). The determination of the oil–water partition coefficient demonstrated that the TM-GC-NPs had a high liposolubility at pH 6 as compared to timolol-loaded chitosan nanoparticles (TM-CS-NPs) and commercial TM eye drops. The in vitro release study indicated that TM-GC-NPs had a sustained release effect compared with the commercial TM eye drops. Ocular tolerance was studied by the hen’s egg chorioallantoic membrane (HET-CAM) assay and the formulation was non-irritant and could be used for ophthalmic drug delivery. The in vitro transcorneal permeation study and confocal microscopy showed enhanced penetration, and retention in the cornea was achieved with TM-GC-NPs compared with the TM-CS-NPs and TM eye drops. Preocular retention study indicated that the retention of TM-GC-NPs was significantly longer than that of TM eye drops. The in vivo pharmacodynamic study suggested TM-GC-NPs had a better intraocular pressure (IOP) lowering efficacy and a prolonged working time compared to commercial TM eye drops (P?≤?0.05). The optimized TM-GC-NPs could be prepared successfully promising their use as an ocular delivery system.