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Loteprednol etabonate is a soft corticosteroid that is rapidly deactivated after reaching the general circulation, displaying good local activity and a high therapeutic index without inducing systemic side effects. In 2021, Kala Pharmaceuticals launched Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% in the U.S. for the short-term (up to 2 weeks) treatment of the signs and symptoms of dry eye disease. Approval by the Food and Drug Administration (FDA) was based on results from one phase II trial and three phase III trials showing Eysuvis significantly improved both the signs and symptoms of dry eye disease and was well tolerated. Eysuvis is a novel loteprednol etabonate nanosuspension formulation developed by Kala using its AMPPLIFY mucus-penetrating particle (MPP) drug delivery technology. Use of this MPP formulation results in enhanced penetration of loteprednol etabonate into target tissue on the ocular surface. Eysuvis is the first FDA-approved ocular corticosteroid indicated for dry eye disease., (Copyright 2022 Clarivate Analytics.)

We report two patients who developed toxic keratopathy following high-dose cytarabine chemotherapy and whose symptoms resolved following topical loteprednol etabonate 0.5% treatment. A 25-year-old woman and a 26-year-old man with acute myeloid leukemia were referred to our department with symptoms of ocular discomfort, photophobia, and blurred vision after consolidation chemotherapy. Central corneal epithelial microcysts were observed bilaterally in both patients, and in vivo confocal microscopy showed highly reflective disseminated granular and irregular intraepithelial opacities, mainly in the basal epithelial layers. Loteprednol etabonate 0.5% relieved both patients' symptoms in less than a week, and the microcysts disappeared in 2 to 3 weeks of treatment. Although there is no standardized treatment protocol for cytarabine-induced corneal toxicity, dexamethasone 0.1% and prednisolone phosphate 1.0% were reported to be effective in the resolution of discomfort and symptoms. In the two patients we report herein, loteprednol etabonate 0.5% four times daily was also effective in suppressing the symptoms.

Dry eye disease (DED) is a common ocular condition that can impair vision and may adversely impact quality of life. Due to the inflammatory nature of this disorder, topical corticosteroids are an effective treatment option, particularly for moderate-to-severe DED when first-line treatments, such as ocular lubricants, are insufficient. Loteprednol etabonate (LE) is a retrometabolically designed corticosteroid with a low propensity to cause corticosteroid-related adverse effects, such as elevated intraocular pressure (IOP). This review was conducted to provide an assessment of published studies on the use of LE for treatment of inflammation associated with DED. Twelve prospective and 2 retrospective studies evaluating LE ophthalmic suspension 0.5% and 2 prospective studies evaluating LE ophthalmic gel 0.5% were identified. LE given as monotherapy or with artificial tears (AT) improved signs of DED, especially among patients with a more pronounced inflammatory component, and also improved DED symptoms compared to baseline and/or control. Treatment with LE before cyclosporine A (CsA) therapy reduced stinging upon CsA initiation and provided more rapid relief of DED signs and symptoms than CsA plus AT alone. In patients with meibomian gland dysfunction, LE alone, or in addition to eyelid scrubs/warm compresses, reduced clinical signs and symptoms, and tear proinflammatory cytokine levels. Overall, LE was safe and well tolerated, with minimal effects on IOP. While larger and longer-term studies are warranted, these data support the use of LE as a safe and effective treatment option for DED.

Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ 1 -cortienic acid (Δ 1 -CA). The simple high-performance liquid chromatography method using acetic acid gradient was developed for the simultaneous determination of LE and its acidic metabolites. LE was hydrolyzed in rat plasma with a half-life of 9 min. However, LE hydrolysis was undetectable in rat liver and intestine. LE hydrolysis in rat plasma was completely inhibited by paraoxon and bis(p-nitrophenyl) phosphate, thus identifying carboxylesterase as the LE hydrolase. Rat plasma carboxylesterase had a K m of 6.7 μM for LE. In contrast to the disappearance rate of LE in rat plasma, the formation rate of 17α-monoester and Δ 1 -CA was markedly low, and a main hydrolysate of LE was not detected in rat plasma. The metabolism of LE proceeded via different pathways in human and rat plasma. LE was slowly hydrolyzed by paraoxonase in human plasma to 17α-monoester with a half-life of 12 h, but by carboxylesterase in rat plasma to yield undetectable products, presumed to include the unstable 17β-monoester.

Introduction: Topical corticosteroids are an important pharmacotherapy for the management of various inflammatory conditions affecting the anterior segment of the eye. However, medications in this class are associated with well-known risks including increased intraocular pressure (IOP) and development of cataracts. The topical corticosteroid loteprednol etabonate (LE) was developed with the specific intention of minimizing these side effects., Areas Covered: The focus of this review is to examine published efficacy and safety data for LE, a drug engineered to undergo rapid metabolism to inactive metabolites with the goal of improved safety. Two decades of clinical research focused on LE formulations are reviewed, including the use of LE in combination with tobramycin. The cumulative body of experience affirms the concept that the molecular design of LE confers certain safety benefits without compromising the desired anti-inflammatory efficacy of a topical corticosteroid., Expert Opinion: Loteprednol etabonate is a mainstay for topical therapy of a wide variety of commonplace and niche conditions of the ocular surface and the anterior segment, including in the healing post-operative patient. Its versatility and safety allow eye care providers to recommend both acute induction as well as chronic maintenance therapy with appropriate follow-up.

The purpose of the present study was to develop loteprednol etabonate (LE) loaded poly(d,l-lactide co-glycolide) (PLGA) nanoparticles (NPs) and study their penetration profile into the excised goat cornea. In the present study, LE loaded PLGA NPs were prepared by solvent evaporation with high speed homogenization method and the penetration profile was studied using confocal laser scanning microscopy (CLSM). Rhodamine (Rd) was used as a fluorescent marker to prepare Rd-LE-PLGA-NPs. The NPs were characterized for particle size, X-ray diffraction (XRD), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), drug entrapment, and permeation profile. Intense fluorescence observed across the depths of goat corneal tissue suggested an improved penetration profile of NPs. The entrapment efficiency and mean diameter of the optimized formulation (F5) were found to be 96.31 ± 1.68% and 167.6 ± 0.37 nm, respectively. These findings indicate that LE loaded PLGA NPs may serve as a potential drug carrier for ocular administration in eye disease.

Loteprednol etabonate (LE) is a soft corticosteroid that maintains therapeutic activity with much reduced adverse effects. Yet, its ocular bioavailability is hindered by its poor aqueous solubility. Early attempts of LE complexation with cyclodextrins (CDs) did not involve the study of the effects of various complexation methods on the characteristics of the complexes formed. Formulation of complexes into different delivery systems as well in vitro and in vivo assessments has not been accomplished in the earlier studies. In this study, complexation of LE with each of hydroxypropyl-β-cyclodextrin (HP-β-CD) and β-cyclodextrin (β-CD) by kneading, freeze drying, and co-precipitation was attempted. These complexes were incorporated into gels, drops, and ocuserts using hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and sodium alginate (ALG). These formulae were examined with respect to drug content, pH, viscosity, in vitro release, and stability for 6 months. Kinetic analysis of release data was done. Selected formulations were assessed for their efficacy in the treatment of ocular allergic conjunctivitis and their ocular bioavailability in rabbits' eyes. All formulations exhibited accepted drug content, pH, and viscosity. The drug release was increased by complexation particularly with HP-β-CD in the order of ocuserts ≥ drops > gels, being the highest for HPMC preparations that also exhibited the greatest stability and anti-inflammatory activity especially in case of LE-HP-β-CD complexes. Ocuserts of co-precipitated LE-HP-β-CD using HPMC (5% w/w) and Carbopol 934P (0.1% w/w) provided a significantly enhanced stability (p < 0.05), ocular anti-inflammatory efficacy (p < 0.05), and ocular bioavailability (p < 0.0001), to be represented as a potential ocular delivery system of LE.

Purpose: To compare the efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T) ophthalmic suspensions in reducing select signs of blepharitis., Methods: Data were pooled from two studies (one from the USA; one from China) of adults (n = 627) with blepharokeratoconjunctivitis treated with LE/T or DM/T four times daily for 2 weeks (safety population). Efficacy analyses included 495 eyes (247 LE/T, 248 DM/T) with any baseline sign of blepharitis., Results: At Day 15, the least squares mean change from baseline in composite blepharitis severity was similar between LE/T (-2.86) and DM/T (-2.99) (90% CI for mean treatment difference: -0.35, 0.11). Intraocular pressure (IOP) increases ≥10 mmHg over baseline were reported for 1 US patient (DM/T group) and 19 Chinese patients (6 LE/T; 13 DM/T)., Conclusions: LE/T was similarly effective in reducing the signs of blepharitis compared with DM/T, but demonstrated a better safety profile with respect to changes in IOP.

The soft drug approach is successful in obtaining high local therapeutic efficacy without systemic adverse effects, because soft drugs are designed to be bioconverted to inactive form by hydrolytic enzymes in systemic circulation. However, there is little information about the exact nature of these metabolic enzymes. In this study, the human enzymes for biotransformation of soft drugs were investigated. Loteprednol etabonate (LE) and etiprednol dicloacetate (ED) were designed from Δ 1 -cortienic acid (Δ 1 -CA), the inactive metabolite of prednisolone, by introducing two labile ester bonds to restore the corticosteroidal activity. We found that LE and ED were mainly deactivated in human plasma rather than the liver. Inactive monoesters were produced, but the second hydrolysis to Δ 1 -CA was much slower. ED was hydrolyzed 10 times faster than LE in plasma (t 1/2 =1.35±0.08, 12.07±0.52h respectively). Paraoxonase 1 that attached with high density lipoprotein (HDL) was found to be the major hydrolase for LE and ED in human plasma as demonstrated by enzyme inhibition and stimulation experiments and the hydrolysis in lipoproteins-rich plasma fractions. Human serum albumin (HSA) showed slight hydrolase activity against ED but not LE. LE was slowly hydrolyzed in liver (clearance: 0.21±0.04 and 2.41±0.13ml/h/kg in liver and plasma, respectively) but ED wasn't hydrolyzed at all, so LE has superior metabolism in two sites. The difficult diffusion of HDL into tissues from blood suggests the stable presence of LE at the administration site, while ED might be deactivated by its relatively rapid chemical hydrolysis and hydrolase activity of HSA, in the interstitial fluid of the administration tissue. Moreover, deactivation in plasma and strong protein binding (around 98%) minimize the adverse effects of LE and ED in the systemic circulation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the study was to determine the concentrations of Flarex ® and Lotemax ® when shaken and not shaken. Many patients fail to shake or inappropriately shake suspensions of corticosteroids before instillation as directed. This study was designed to help determine what concentration of corticosteroid these patients are receiving. In addition, independent confirmation of loteprednol etabonate ophthalmic gel dose uniformity was determined and compared as a possible alternative., Methods: Drug concentrations of shaken versus unshaken Flarex and Lotemax were determined over a 20-day simulated tapered course in our institutional laboratory. Collected samples were analyzed by reversed-phase high-performance liquid chromatography with photodiode array detection at 240 nm., Results: Flarex had a mean concentration of 93.7% of the declared concentration when shaken and 7.25% when not shaken. The difference between these groups was statistically significant (P = 0.0001). Lotemax had a mean concentration of 96.74% of the declared concentration when shaken and a mean concentration of 98.97% when not shaken. The difference between these groups was not statistically significant (P = 0.194)., Conclusions: Flarex maintains dose uniformity when shaken. When not shaken, it has poor dose uniformity. Lotemax was consistent whether shaken or not in our study and can be considered to eliminate the variability of poor patient compliance with shaking. The manufacturers of both drugs recommend shaking before application.

Background: Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications., Methods: The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied., Results: The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively., Conclusion: The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A novel cationic nanoemulsified in-situ ophthalmic gel of loteprednol etabonate (LE) was developed to improve the permeability and retention time of formulations for overall improvement of drug's ocular bioavability. Capryol 90 (oil phase), tween 80 (surfactant) and transcutol P (cosurfactant) was selected as formulation excipients to construct pseudoternary phase diagrams and nanoemulsion region was recognized from diagrams. Spontaneous emulsification method was used to manufacture LE nanoemulsion and it was optimized using 3 2 factorial design by considering the amount of oil and the ratio of surfactant to cosurfactant (S mix ) as independent variables and evaluated for various physicochemical properties. Optimized NE was dispersed in Poloxamer 407 and 188 solution to form nanoemulsified sols that were predictable to transform into in-situ gels at corneal temperature. Drug pharmacokinetics of sterilized optimized in situ NE gel, NE-ISG2 [0.69% w/w Capryol 90, 0.99%w/w S mix (3:1), 13% Poloxamer 407, 4% w/w Poloxamer 188] and marketed formulation were assessed in rabbit aqueous humor. The in-situ gels were clear, shear thinning in nature and displayed zero-order drug release kinetics. NE-ISG2 showed the minimum ocular irritation potential and significantly (p < 0.01) higher C max and AUC (0-10 h) , delayed T max , extended mean residence time and improved (2.54-fold times) bioavailability compared to marketed formulation.

Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations-including a gel, an ointment, and a suspension of LE in combination with tobramycin-have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.

This study reports on the development of a novel mucoadhesive and biocompatible shell-crosslinked nanogel system based on poly(butylene adipate) (PBA) and N-succinyl chitosan (S-Cs) by coupling reaction with a new formulation method. For this purpose, two different molecular weights of dendrimerized PBA with amine terminated functional groups were synthesized separately and characterized well by FT-IR, (1)HNMR and GPC. The PBA nanoparticles containing loteprednol etabonate (LPE) prepared by O/W emulsion technique were reacted immediately with modified carboxylated chitosan via carbodiimide chemistry. TEM photographs of the nanoparticles and crosslinked nanoparticles displayed a spherical morphology closely corresponding to the results obtained by DLS. On The other hand, biodegradability, biocompatibility and bioadhesiveness of the prepared nanoparticles were also studied. It is concluded that the core-shell structured nanogels can be used as novel ocular drug delivery systems with appropriate loading capacity for slightly water soluble LPE as an anti-inflammatory drug., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: This meta-analysis was designed to assess the efficacy, as well as the safety of loteprednol etabonate (LE) ophthalmic suspension compared with placebo and other commonly used eye drops for treatment of allergic conjunctivitis., Methods: Comprehensive searches of randomized controlled trials were carried out in a database of Medline, Embase, and the Cochrane Library. Eight qualified studies were included. This study assessed the reduction from baseline in scores of cardinal signs and symptoms, proportion of patients with improvement of allergic signs and symptoms, and incidence of clinically significant intraocular pressure (IOP) elevation (IOP elevation ≥10 mmHg)., Results: The results showed that topical LE was significantly superior to placebo in reduction from baseline in signs scores (standardized mean difference [SMD] = -0.48; 95% confidence interval [CI] = -0.65 to -0.32) and symptoms scores (weighted mean difference [WMD] = -0.51; 95% CI = -0.64 to -0.38) of allergic conjunctivitis, and as effective as olopatadine and fluorometholone acetate. Topical LE was associated with a higher improvement rate of signs (risk ratio [RR] = 1.53; 95% CI = 1.26-1.86; I (2 )= 57%) and symptoms (RR = 1.29; 95% CI = 1.15-1.46; I (2 )= 54%) than placebo and the positive control treatment. Clinically significant IOP elevation was more frequent in the group of LE than the group of control treatment (pooled odds ratio = 3.03; 95% CI = 1.04-8.80), which was affected by the response to corticosteroid of the individual patient and the wearing of contact lenses., Conclusions: Topical LE is effective in treating allergic conjunctivitis. However, it should be used with caution due to the higher incidence of IOP elevation compared with placebo and olopatadine. A large-scale trial would be required to confirm the effect of different concentrations of LE on IOP.

Ciprofloxacin hydrochloride being a fluoroquinolone antibacterial drug is very frequently preferred in the treatment of bacterial conjunctivitis by the eye specialists. Addition of loteprednol etabonate only adds up to the anti-inflammatory activity of the developed formulation. The objective of the present work was to develop ocular inserts of ciprofloxacin hydrochloride with loteprednol etabonate and further evaluate its potential as a sustained novel ocular drug delivery system. Ophthalmic solutions, suspensions are known for its poor bioavailability and poor therapeutic responses due to many pre-corneal constraints. The researchers usually get triggered with these constrains and strive to formulate controlled and sustained drug delivery system. Ocular inserts based on solvent cast technique were formulated and characterized for in vitro drug release studies using a flow through apparatus that simulated the eye conditions. Compatibility of ciprofloxacin hydrochloride, loteprednol etabonate, polymer and excipients were checked as preliminary preformulation studies. Different combinations of ciprofloxacin hydrochloride, loteprednol etabonate, carbopol 974, 980, 981, polyethylene glycol 400 and glycerine were formulated by solvent cast method and optimized on was evaluated. Fabricated ocuserts were evaluated for its clarity, smoothness, surface pH, drug content and in vitro drug release study to find the optimized film. Formula ciprofloxacin hydrochloride with loteprednol etabonate and carbopol 980 was found to be the best formulation fulfilling the needs of all organoleptic parameters and also the in vitro release study. Based on in vitro correlation and stability studies, it was concluded that this ocular insert formulation could be a promising controlled release formulation for the researchers. [ABSTRACT FROM AUTHOR]

CYP3A is one of the most important classes of enzymes and is involved in the metabolism of over 70% drugs. While several selective CYP3A4 inhibitors have been identified, the search for a selective CYP3A5 inhibitor has turned out to be rather challenging. Recently, several selective CYP3A5 inhibitors have been identified through high-throughput screening of ~ 11,000 compounds and hit expansion using human recombinant enzymes. We set forth to characterize the three most selective CYP3A5 inhibitors in a more physiologically relevant system of human liver microsomes to understand if these inhibitors can be used for reaction phenotyping studies in drug discovery settings. Gomisin A and T-5 were used as selective substrate reactions for CYP3A4 and CYP3A5 to determine IC50 values of the two enzymes. The results showed that clobetasol propionate and loteprednol etabonate were potent and selective CYP3A5 reversible inhibitors with selectivity of 24-fold against CYP3A4 and 39-fold or more against the other major CYPs. The selectivity of difluprednate in HLM is much weaker than that in the recombinant enzymes due to hydrolysis of the acetate group in HLM. Based on the selectivity data, loteprednol etabonate can be utilized as an orthogonal approach, when experimental fraction metabolized of CYP3A5 is greater than 0.5, to understand CYP3A5 contribution to drug metabolism and its clinical significance. Future endeavors to identify even more selective CYP3A5 inhibitors are warranted to enable accurate determination of CYP3A5 contribution to metabolism versus CYP3A4. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common condition that affects mainly older individuals and women. It is characterized by reduced tear production and increased tear evaporation. Symptoms include burning, irritation, tearing, and blurry vision. This paper reviews key trials of various new DED treatments, including their mechanism of action, study outcomes, safety, and efficacy. The paper also includes a critical assessment of the trial's validity and potential pharmacy applications of these new treatments. The literature search was conducted through PubMed, the Cochrane Central Register of Controlled Trials, and Google Scholar. The keywords "Dry Eye Disease", "lifitegrast", "cyclosporine", "loteprednol etabonate", "varenicline nasal spray", and "perfluorohexyloctane" were used to identify these medications' landmark trials. The articles deemed these medications safe and efficacious, with minimal side effects. Our randomized controlled trial validity comparison found the trials robust with predominantly low bias. Cyclosporine and loteprednol are effective when artificial tears fail, while perfluorohexyloctane reduces tear film evaporation and is preservative-free. Varenicline offers drug delivery via the nasal route and is appropriate for contact lens users. In conclusion, these FDA-approved novel medications exhibit safety and efficacy in managing DED. Further research is needed on long-term outcomes, efficacy, and side-effect comparisons, and combination therapy benefits. [ABSTRACT FROM AUTHOR]

Ophthalmic films are the best sustained-release ocular drug delivery system. The present study targets developing such ocular films of antibacterial with corticosteroid and evaluating its potential. Conventional ocular dosage forms have low bioavailability with low therapeutic response. The solvent cast method employed in ophthalmic films has triggered the minds of researchers to design sustained drug delivery systems overcoming pre-corneal constraints. The compatibility of antibacterial with Loteprednol Etabonate added polymers, excipients were evaluated through preformulation studies. Different combinations of ocular inserts with antibacterial drug and corticosteroid, excipients were formulated and evaluated. Formula CLE 80 (Ciprofloxacin Hydrochloride with Loteprednol Etabonate) fulfilled the needs of all organoleptic parameters like appearance, texture, surface pH, drug content, and in-vitro studies. The results predicted CLE 80 ophthalmic film would be a promising controlled-release formulation for better patient compliance. [ABSTRACT FROM AUTHOR]

A simple, precise and accurate ultraviolet-visible spectrophotometer method has been developed by applying ratio spectra derivative method and validated for the simultaneous estimation of moxifloxacin hydrochloride and loteprednol etabonate from ophthalmic formulation. Absorbance of moxifloxacin hydrochloride and loteprednol etabonate was recorded at their respective wavelength and then zero order spectra was converted to first order derivative spectra after dividing respective zero order spectra with divisor concentration. Developed method was linear at concentration range 4-20 μg/ml, (r²=0.99) and (r²=0.99), for loteprednol etabonate and moxifloxacin hydrochloride respectively. The linear regression equations were y=0.005x+0.001 for loteprednol etabonate and y=0.118x-0.062 for moxifloxacin hydrochloride. The results of analysis were validated which showed that proposed method was simple, precise and accurate. [ABSTRACT FROM AUTHOR]

Purpose: To perform a systematic evaluation of the efficacy and safety of loteprednol etabonate (LE) 0.5% versus fluorometholone (FML) 0.1% for treating patients after corneal refractive surgery with the aim of providing an evidence-based rationale for clinical drug selection. Methods: Electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, WanFang, and CNKI) were searched (from inception to December 2021) for comparative clinical studies that evaluated LE versus FML treatment for post-corneal refractive surgery patients. Meta-analysis was performed using the RevMan 5.3 software. The pooled risk ratio (RR) and weighted mean difference (WMD) with corresponding 95% confidence interval (CI) were calculated. Results: Nine studies with a total sample size of 2677 eyes were included in this analysis. FML 0.1% and LE 0.5% produced a similar incidence of corneal haze within 6 months after surgery (P = 0.13 at 1 month, P = 0.66 at 3 months, and P = 0.12 at 6 months). There was no statistically significant difference between the two groups in terms of the mean logMAR postoperative uncorrected distance visual acuity (WMD: − 0.00; 95% CI: − 0.01 to 0.00; P = 0.29) and spherical equivalent (WMD: 0.01; 95% CI: − 0.01 to 0.03; P = 0.35). LE 0.5% appears to have a higher tendency to reduce the incidence of ocular hypertension compared FML 0.1%, but there was no statistical significance (RR: 0.63; 95% CI: 0.27 to 1.50; P = 0.30). Conclusion: This meta-analysis demonstrated that LE 0.5% and FML 0.1% had comparable efficacy in preventing corneal haze and corticosteroid-induced ocular hypertension, with no difference in visual acuity in patients after corneal refractive surgery. [ABSTRACT FROM AUTHOR]

The treatment of several ocular inflammatory conditions affecting different areas of the ocular globe involves the administration of topical ophthalmic formulations containing corticosteroids. This research was aimed at evaluating the solubilising efficacy of 5.0% w/w of different binary mixtures of commercial amphiphilic polymeric surfactants with the purpose of obtaining nanomicellar solutions containing a high amount of loteprednol etabonate (LE). The selected LE-TPGS/HS nanomicelles, containing 0.253 mg/mL of the drug, had a small size (=13.57 nm) and uniform distribution (Polydispersity Index = 0.271), appeared completely transparent and perfectly filterable through 0.2 μm membrane filter, and remained stable up to 30 days at 4 °C. The critical micellar concentration (CMCTPGS/HS) was 0.0983 mM and the negative value of the interaction parameter between the polymeric-surfactant-building unit (βTPGS/HS = −0.1322) confirmed the ability of the polymeric surfactants to interact, favouring the dissolution of LE into nanomicelles. The disappearance of the endothermic peak of LE in the DSC analysis confirmed the interactions of LE with the polymeric surfactants. LE-TPGS/HS produced in vitro LE which sustained diffusion for 44 h (more than 40% of encapsulated LE). Furthermore, the lack of a significant cytotoxic effect on a sensitive corneal epithelial cell line makes it a candidate for further biological studies. [ABSTRACT FROM AUTHOR]

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common condition that affects mainly older individuals and women. It is characterized by reduced tear production and increased tear evaporation. Symptoms include burning, irritation, tearing, and blurry vision. This paper reviews key trials of various new DED treatments, including their mechanism of action, study outcomes, safety, and efficacy. The paper also includes a critical assessment of the trial’s validity and potential pharmacy applications of these new treatments. The literature search was conducted through PubMed, the Cochrane Central Register of Controlled Trials, and Google Scholar. The keywords “Dry Eye Disease”, “lifitegrast”, “cyclosporine”, “loteprednol etabonate”, “varenicline nasal spray”, and “perfluorohexyloctane” were used to identify these medications’ landmark trials. The articles deemed these medications safe and efficacious, with minimal side effects. Our randomized controlled trial validity comparison found the trials robust with predominantly low bias. Cyclosporine and loteprednol are effective when artificial tears fail, while perfluorohexyloctane reduces tear film evaporation and is preservative-free. Varenicline offers drug delivery via the nasal route and is appropriate for contact lens users. In conclusion, these FDA-approved novel medications exhibit safety and efficacy in managing DED. Further research is needed on long-term outcomes, efficacy, and side-effect comparisons, and combination therapy benefits.

Objective: This study served to compare the degree of adrenocortical suppression following a 2‐week administration of loteprednol etabonate (LE) and prednisolone acetate (PA) ophthalmic drops. Procedures: In this prospective double‐masked triple‐crossover study, 21 clinically healthy dogs were randomized to receive loteprednol etabonate ophthalmic suspension 0.5%, prednisolone acetate ophthalmic suspension 1%, or artificial tears (AT). Each group (LE, PA, and AT) received one drop in each eye every 12 h for 2 weeks, followed by a 3‐week washout period between treatment blocks. ACTH stimulation tests were performed before and after each treatment block. Serum cortisol samples were drawn before and 60 min after administration of 1 μg/kg cosyntropin IV. Repeated‐measurement ANOVA followed by a Tukey's multiple comparisons test (or a Friedman test followed by a Dunn's multiple comparisons test) were used to compare pre‐ and post‐treatment cortisol values between each group. A p‐value of ≤.05 was considered significant. Results: A total of 18 dogs completed the study. Prestimulation cortisol values were lower in the PA group compared to the LE (p =.0106), but not AT (p =.0589) groups, and post‐stimulation cortisol values were lower in the PA group than either LE (p =.0005) or AT (p =.0002) groups. There was no significant difference detected in pre‐ or post‐stimulation cortisol values after the treatment periods between LE and AT. Conclusions: Based on the reduced suppression of cortisol values, LE caused significantly less hypothalamic–pituitary–adrenal axis suppression than PA. A topical steroid with minimal adrenocortical suppression, such as LE, may be favorable in patients where systemic glucocorticoid effects should be avoided. [ABSTRACT FROM AUTHOR]