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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]

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.

Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve transdermal LE delivery for the first time. SLN and NLC were produced by hot homogenisation and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. It was determined that SLN and NLC mean particle size of 139.1 nm had a homogeneous particle size distribution (∼0.169 PI) and the mean charge was −23.6. They were found to be stable both physically and chemically at room temperature. SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with fewer side-effects in the treatment of inflammatory problems. [ABSTRACT FROM AUTHOR]

The aim of present study was to prepared ocular in-situ gel to increase the residence time of drug in cornea for improvement of ocular bioavailability of drug. In situ gel of Loteprednol etabonate was prepared by using carobopol 940 and different grades of HPMC in different ratios by pH triggered method. The prepared in situ gels were evaluated for pH, drug content, viscosity, gelling time, gelling strength spreadability and sterility testing. In vitro drug release study was carried by using diffusion cell with dialysis membrane. The drug content and pH of the formulation were found to be satisfactory. The gelling strength was found to be in the range of 34 seconds to 91 seconds. The viscosity and spredability of the formulations were found to be satisfactory. Formulation F5 containing 0.3 % carobopol 940 and 0.6 % HPMC K4M showed highest drug release of 80.30 %. The developed formulations showed sustained release of drug up to 8 hrs. From in-vitro drug release studies, it could be concluded that the developed in-situ gelling systems were thus a better alternative to conventional eye drops.

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.

Background: The objective of this work is to develop and validate a reverse-phase HPLC method for determining Loteprednol Etabonate in self micro emulsifying drug delivery systems at nanogram level. Methods: A systematic approach has been implemented for the optimization of chromatographic conditions. The developed reverse-phase HPLC method was validated for linearity, accuracy, precision, limit of detection and quantification, extraction recovery, specificity (matrix effect and forced degradation studies), and robustness. The method was also investigated for the estimation of Loteprednol under forced degradation for acid, base, thermal and oxidative conditions. Results: The developed method showed linearity between 200 and 12000 ng/mL with R 2 value of 0.998. The detection and quantification limits were determined to be 60 and 180 ng/mL, respectively. The % recovery and % RSD of the developed method were 99.00 % to 101.79 % and 0.0459 % - 0.6470 %, respectively. The validated method was able to identify the degradants and formulation excipients interactions at the drug peak retention time (4.7 min). The assay determination in lipid emulsion formulations was successfully carried out using the established method. The % recovery of loteprednol etabonate from formulations has shown good agreement without any interference. Conclusion: The validated stability-indicating analytical method was useful for the quantification of loteprednol etabonate in self micro emulsifying drug delivery systems. [ABSTRACT FROM AUTHOR]

Introduction: Loteprednol etabonate (submicron) ophthalmic gel 0.38% (LE SM gel 0.38%) is a corticosteroid formulation designed to retain the nonsettling characteristics of loteprednol etabonate ophthalmic gel 0.5%, but with reduced drug particle size to improve ocular penetration, allowing for reduced dosing frequency. This study compared the dose uniformity of LE SM gel 0.38% with branded and generic prednisolone acetate (PA) 1% suspensions under simulated in-use dosing conditions. Methods: Drug concentrations in drops of LE SM gel 0.38% and PA 1% suspensions, expressed from bottles that were shaken or not shaken, were determined during 2 weeks of simulated on-label dosing (LE SM gel 0.38%: three times daily; PA suspensions: four times daily). Sedimentation of drug particles was assessed for each product using dispersion analysis. Results: The mean (SD) percent declared drug concentration of LE SM gel 0.38% over 2 weeks was 103.2% (1.3%) when the drug was dispensed from shaken bottles and 103.3% (1.5%) when dispensed from unshaken bottles. However, for branded and generic PA suspensions, mean (SD) percent declared concentrations were 102.2% (1.4%) and 98.3% (2.9%), respectively, when dispensed from shaken bottles; and 89.2% (18.6%) and 78.3% (13.5%), respectively, when dispensed from unshaken bottles. Dispersion analysis showed that drug particles in LE SM gel 0.38% remained fully suspended under accelerated sedimentation conditions, whereas both branded and generic PA suspension drug particles settled out of suspension. Conclusions: LE SM gel 0.38% delivered the drug consistently at the declared concentration over the entire 2 weeks of simulated in-use dosing conditions, regardless of whether the drug was dispensed from shaken or unshaken bottles. However, both branded and generic PA suspensions required the bottle to be shaken to provide a consistent drug concentration. [ABSTRACT FROM AUTHOR]

Use of a combination corticosteroid and antibiotic in a single formulation is common in the treatment of ocular inflammatory conditions for which corticosteroid therapy is indicated and there exists a risk of superficial bacterial infection. Loteprednol etabonate (LE) is a corticosteroid engineered to maintain potent anti-inflammatory activity while minimizing the risk of undesirable class effects of corticosteroids, such as elevated intraocular pressure and cataract. Tobramycin is a broad-spectrum aminoglycoside antibiotic that is considered generally safe and well tolerated. An ophthalmic suspension combining LE 0.5% and tobramycin 0.3% (LE/T) is approved in the US and several other countries. Use of a combination therapy increases convenience, which may promote patient adherence. A systematic literature review was conducted to examine the efficacy and safety of LE/T for ocular inflammatory conditions within the scope of its labeled indications. Results of published studies indicate that LE/T is effective in the treatment of blepharokeratoconjunctivitis in adults, with similar efficacy as dexamethasone 0.1%/tobramycin 0.3%, but is associated with a lower risk of clinically significant increases in intraocular pressure as demonstrated in both efficacy and safety studies and studies with healthy volunteers. Furthermore, studies in children with blepharitis or blepharoconjunctivitis indicate LE/T was well tolerated in this population, although efficacy vs vehicle was not demonstrated, potentially due to improvements in all groups overall and/or limited sample size. Separately, tobramycin demonstrated potent in vitro activity against most bacterial species associated with blepharitis. In conclusion, published data demonstrate the utility of LE/T for the treatment of the various clinical manifestations of blepharokeratoconjunctivitis in adults. [ABSTRACT FROM AUTHOR]