Loteprednol Research Articles

Effect of 0.1% diclofenac ophthalmic solution oninflammatory response and macular thickness following phacoemulsification cataract surgery.

To evaluate 0.1% diclofenac sodium as an adjunctive therapy with loteprednol etabonate on postoperative inflammation in the anterior chamber and on foveal and parafoveal retinal thickness. Eighty eyes eligible for phacoemulsification were enrolled in a randomized clinical trial. Patients in group I (N = 40) received anti-inflammatory treatment consisting of 0.1% diclofenac with 0.5% loteprednol; group II (N = 40) patients received 0.5% loteprednol alone. Best corrected visual acuity and intraocular pressure were measured, and laser flarephotometry was done. Foveal and parafoveal thickness were assessed by optical coherence tomography. Results: Median flare values decreased more rapidly in group I at 7 and 14 days (7.9 and 7.4 ph/ms, respectively) than ingroupII (13.7 and 11.8 ph/ms, respectively; p < 0.0001). Group II had significantly increased parafoveal thickness at 14 and 42 days (median 285.59 μm, p = 0.001 and 288.38 μm, p < 0.001, respectively). Parafoveal thickness differed significantly between groups at 14 and 42 days (p = 0.0085, p = 0.0004, respectively). Eyes treated with both diclofenac sodium and loteprednol etabonate showed less inflammatory response andwere less likely to develop foveal and parafoveal thickening than those treated with steroid only.

Effect of topical loteprednol etabonate with lid hygiene on tear cytokines and meibomian gland dysfunction in prosthetic eye wearers.

PurposeTo assess tear cytokine levels and clinical outcomes in meibomian gland dysfunction (MGD) in the blind eye of patients wearing an ocular prosthesis after 2 months of treatment with topical loteprednol etabonate and eyelid scrubs with warm compresses.Patients and methodsThis study included patients with MGD wearing a unilateral ocular prosthesis for more than 1 year. All patients topically received 0.5% loteprednol etabonate and were instructed to scrub their eyelids with warm compresses on the prosthetic eye for 2 months. We evaluated tear cytokine levels using Multiplex Bead Immunoassays, performed biomicroscopic examination of the lid margins and meibomian gland, conducted meibography imaging, and assessed MGD-related ocular symptoms using a questionnaire for the prosthetic eye before and 2 months after treatment.ResultsThirty consecutive patients were included. There were significant reductions in the levels of interleukin (IL)-6, interferon-γ, monocyte chemotactic protein-1, IL-8, tumor necrosis factor-α, and IL-1β (P<0.001 for each cytokine). Moreover, there were improvements in ocular symptoms (P=0.001), lid margin abnormalities (P<0.001), meibomian gland expressibility (P<0.001) and meibography findings (P=0.037).ConclusionTopical loteprednol etabonate in conjunction with eyelid scrubs and warm compresses were effective in treating MGD in prosthetic eye wearers. Furthermore, tear cytokine measurements may serve as an additional approach for evaluating the efficacy of anti-inflammatory treatment for MGD in prosthetic eye wearers.

Softacort®, preservative‐free hydrocortisone 0.335% drops: A new anti‐inflammatory drop with minimal effects on intraocular pressure

PurposeThe aim of this study was to compare the changes in intraocular pressure (IOP) after instillation of a new preservative‐free hydrocortisone 0.335%(Softacort®), prednisolone 1% (Inflanefrane® Forte), loteprednol etabonate 0.5% (Lotemax®) and rimexolone 1% (Vexol®) in comparison with dexamethasone 0.1% (Maxidex®) in a rat model of glucocorticoid‐induced ocular hypertensionMethodsSixty albino female rats were divided into 5 treatment groups and drops administered twice daily from Day 1 to Day 36. Clinical examination, body weight, and IOP measurements were assessed once weekly during 5 weeks.ResultsAnimals treated with Softacort®, Lotemax® or Vexol® had a similar body weight gain. Inflanefran® Forte‐treated animals showed a lower body weight gain. Maxidex®‐treated animals gained weight up to 7 days but there after lost weight as expected. Animals treated with Softacort®, Lotemax®, Inflanefran® Forte or Vexol® had a similar IOP profile with a slow increase in the mean IOP up until Day 15, and then stabilization at +2 mmHg above baseline throughout the remainder of the study Maxidex®‐treated animals showed, as expected, an increase of the mean IOP until Day 36 reaching +4.4 mmHg and progressively increasing.ConclusionsThis study shows significant differences in the IOP rise and therefore greater safety of this new preservative‐free hydrocortisone and other soft corticoids when compared to Maxidex. Twice daily instillation of Softacort® induced a slight IOP elevation which stabilized after 2‐weeks whilst dexamethasone treatment led to a significant continuing IOP increase and drastically reduced body weight gain. Thus, Softacort®, a preservative free hydrocortisone 0.335%, shows a good balance between efficacy and minimal side effects and has just obtained the Marketing Authorization in Europe.

Loteprednol Etabonate Nanoparticles: Optimization via Box-Behnken Design Response Surface Methodology and Physicochemical Characterization

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. 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. 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. 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.

Efficacy and safety of a 3-month loteprednol etabonate 0.5% gel taper for routine prophylaxis after photorefractive keratectomy compared to a 3-month prednisolone acetate 1% and fluorometholone 0.1% taper

PurposeTo compare the outcome of photorefractive keratectomy (PRK) and complications in patients treated with either loteprednol etabonate 0.5% gel or prednisolone acetate 1% suspension and fluorometholone (fml) 0.1% suspension.SettingJohn A Moran Eye Center, University of Utah, Salt Lake City, UT, USA.DesignProspective, randomized, partially masked trial.MethodsPRK was performed on 261 eyes of 132 participants. Patients were randomized to a postoperative corticosteroid regimen of either loteprednol etabonate 0.5% gel (loteprednol) or prednisolone 1% acetate suspension followed by fluorometholone 0.1% suspension (prednisolone/fml). Primary outcome measures included incidence and grade of postoperative corneal haze and incidence of increased intraocular pressure of 10 mmHg above baseline, or any intraocular pressure over 21 mmHg. Secondary outcome measures included uncorrected distance visual acuity, best corrected distance visual acuity, and manifest refraction spherical equivalent.ResultsThe incidence of haze in the first 3 months was 2.6% (3/114 eyes) in the loteprednol group and 4.8% (7/147 eyes) in the prednisolone/fml group and was not statistically significant between groups (P=0.37). The incidence of elevated intraocular pressure was 1.8% (2/114 eyes) in the loteprednol group and 4.1% (6/147 eyes) in the prednisolone/fml group, and was not statistically significant between the groups (P=0.12). The mean 3-month postoperative logMAR uncorrected visual acuity was −0.078±0.10 and −0.075±0.09 in the loteprednol and prednisolone/fml groups, respectively (P=0.83).ConclusionPostoperative corneal haze and elevated intraocular pressure were uncommon in both treatment arms. There was no statistically significant difference between each postoperative regimen. Refractive results were similar and excellent in both treatment arms. A tapered prophylactic regimen of loteprednol 0.5% gel is equally effective to prednisolone 1%/fml 0.1% after PRK.

Physicochemical attributes and dissolution testing of ophthalmic ointments

The investigation of semisolid ophthalmic ointments is challenging due to their complex physicochemical properties and the unique anatomy of the human eye. Using Lotemax® as a model ophthalmic ointment, three different manufacturing processes and two excipient sources (Fisher® (OWP) and Fougera® (NWP)) were used to prepare loteprednol etabonate ointments that were qualitatively and quantitatively the same across the manufactured formulations. Physicochemical properties including drug content and uniformity, particle size and distribution, as well as rheological parameters (onset point, crossover modulus, storage modulus and Power law consistency index) were investigated. In addition, USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the ophthalmic ointments. Both manufacturing processes and excipient sources had a significant influence on the physicochemical attributes and the in vitro drug release profiles of the prepared ointments. Ointments prepared via the hot melt processes exhibited higher rheological parameters and lower drug release rates compared to ointments prepared without hot melting. Ointments prepared with OWP demonstrated higher rheological parameters and lower in vitro drug release rates compared to ointments prepared with NWP. A strong correlation between the rheological parameters and in vitro drug release rate was shown using logarithmic linear regression. This correlation may be useful in predicting in vitro drug release from measured physicochemical properties, and identifying the critical quality attributes during the development of ointment formulations.

Topical treatments for blepharokeratoconjunctivitis in children.

Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia.Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation. Although both topical and systemic treatments are used to treat people with BKC, this Cochrane review focuses on topical treatments. To assess and compare data on the efficacy and safety of topical treatments (including antibiotics, steroids, immunosuppressants and lubricants), alone or in combination, for BKC in children from birth to 16 years. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE ( January 1946 to 11 July 2016), Embase (January 1980 to 11 July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We searched the reference lists of identified reports and the Science Citation Index to identify any additional reports of studies that met the inclusion criteria. We searched for randomised controlled trials that involved topical treatments in children up to 16 years of age with a clinical diagnosis of BKC. We planned to include studies that evaluated a single topical medication versus placebo, a combination of treatments versus placebo, and those that compared two or multiple active treatments. We planned to include studies in which participants received additional treatments, such as oral antibiotics, oral anti-inflammatories, warm lid compresses and lid margin cleaning. Two review authors independently screened the results of the literature search (titles and abstracts) to identify studies that met the inclusion criteria of the review and applied standards as expected for Cochrane reviews. We graded the certainty of the evidence using GRADE. We included one study from the USA that met the inclusion criteria. In the study, 137 children aged zero to six years old with blepharoconjunctivitis were randomised to treatment in one of four trial arms (loteprednol etabonate/tobramycin combination, loteprednol etabonate alone, tobramycin alone or placebo) for 15 days, with assessments on days 1, 3, 7 and 15. We judged the study to be at high risk of attrition bias and bias due to selective outcome reporting. The study did not report the number of children with improvement in symptoms nor with total or partial success as measured by changes in clinical symptoms.All children showed a reduction in blepharoconjunctivitis grade score, but there was no evidence of important differences between groups. Visual acuity was not fully reported but the authors stated that there was no change in visual acuity in any of the treatment groups. The study reported ocular and non ocular adverse events but was underpowered to detect differences between the groups. Ocular adverse events were as follows: loteprednol/tobramycin 1/34 (eye pain); loteprednol 4/35 (eye pain, conjunctivitis, eye discharge, eye inflammation); tobramycin 0/34; placebo (vehicle) 0/34. The evidence was limited for all these outcomes and we judged it to be very low certainty.There was no information on clinical signs (aside from grade score), disease progression or quality of life. There is no high-quality evidence of the safety and efficacy of topical treatments for BKC, which resulted in uncertainty about the indications and effectiveness of topical treatment. Clinical trials are required to test efficacy and safety of current and any future treatments. Outcome measures need to be developed which can capture both objective clinical and patient-reported aspects of the condition and treatments.

Dose Uniformity of Topical Corticosteroids: A Simulated Trial of Fluorometholone Acetate 0.1% and Loteprednol Etabonate Gel 0.5.

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. 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. 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). 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.

Comparison of the Safety and Efficacy of Loteprednol Etabonate 0.5%/Tobramycin 0.3% with Dexamethasone 0.1%/Tobramycin 0.3% Following Strabismus Surgery.

To compare the anti-inflammatory efficacy and safety of 0.5% loteprednol etabonate/0.3% tobramycin (LE/T) and 0.1% dexamethasone/0.3% tobramycin (DM/T) ophthalmic suspensions following strabismus surgery. The records of 40 patients who were treated with either LE/T or DM/T following strabismus surgery were retrospectively reviewed. The recorded signs and symptoms of inflammation and intraocular pressure of the patients at 1 day, 1 week, and 3 weeks after the surgery were evaluated and compared between the groups. In both groups, reduced inflammation was noted during the follow-up visits. There was no statistically significant difference between the LE/T and DM/T groups with regard to the postoperative scores or measurements, including discomfort, chemosis, secretion, conjunctival hyperemia, and conjunctival gap size (p>0.05), during the follow-up visits. Allergic reactions to the medications were not reported in any patient. Intraocular pressures were within normal limits in both groups. LE/T was found to be as effective as DM/T in reducing inflammation after strabismus surgery. LE/T, as a new-generation steroid combination product, could be used as a safe and effective anti-inflammatory agent for the treatment of inflammation following strabismus surgery.

Identification of esterase involved in the metabolism of two corticosteroid soft drugs

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 Δ1-cortienic acid (Δ1-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 Δ1-CA was much slower. ED was hydrolyzed 10 times faster than LE in plasma (t1/2=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.

Efficacy of olopatadine hydrochloride 0.1%, emedastine difumarate 0.05%, and loteprednol etabonate 0.5% for Chinese children with seasonal allergic conjunctivitis: a randomized vehicle-controlled study.

BackgroundAllergic conjunctivitis (AC) is a disease of various agents that affects the physical and mental health of children. Although the most effective therapy has not been found so far, it is essential to explore the considerable therapeutic method. We compared the clinical efficacy of olopatadine, emedastine, loteprednol etabonate (LE), and vehicle for treating seasonal allergic conjunctivitis (SAC) in Chinese children.MethodsEighty cases of 160 eyes aged from 5 to 10 years with SAC were available and those subjects were randomly distributed into 4 groups. Both their eyes received olopatadine hydrochloride 0.1% twice a day, emedastine difumarate 0.05% twice a day, or LE 0.5% 4 times a day, respectively, whereas those of the control group received artificial tears (AT) 0.5% 3 times a day. This study was conducted successfully and the observations were collected before treatment and on day 8 (±1 day) and day 15 (±2 days) afterward. The principal measurement of efficacy was focused on the signs and symptoms of the subjects, evaluated before and after treatment, in addition to visual acuity (VA) and fundus oculi.ResultsOn day 8 (±1 day) and day 15 (±2 days), all the antiallergic agents were found to be more effective than vehicle (p < 0.05) in terms of all the symptoms and signs. However, there was no statistical significance (p ≥ 0.05) shown among the treatment groups. There were no evident changes in VA and no clinically significant changes were observed in fundus oculi.ConclusionAfter the treatment, the efficacy presented a similar distribution among the trial groups.

Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability

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 32 factorial design by considering the amount of oil and the ratio of surfactant to cosurfactant (Smix) 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 Smix (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 Cmax and AUC(0–10 h), delayed Tmax, extended mean residence time and improved (2.54-fold times) bioavailability compared to marketed formulation.

Updates on the Treatment of Pterygium

Abstract Pterygium is an ocular disease characterised by the growth of fibrovascular conjunctiva on the cornea. It occurs more often in men, at an older age, and in individuals exposed to ultraviolet radiation. Surgical treatment is the primary treatment for pterygium and there are two common procedures for pterygium excision. In the first method, the head of the pterygium is separated from the corneal surface using a surgical blade. The second method is based on avulsion. Other approaches to excising the pterygium include the use of argon laser and excimer laser. Because of a high recurrence rate, adjuvant therapies, including radiotherapy, chemotherapy, and graft procedures, are used after pterygium excision. These procedures have become the standard long-term treatments for pterygium. Radiotherapy is based on beta irradiation. Chemotherapy includes the use of mitomycin C, 5-fluorouracil, bevacizumab, and loteprednol etabonate. Graft procedures include amniotic membrane grafts and conjunctival autografts. Many surgeons believe that using mitomycin C and conjunctival autografts provides the best outcomes in terms of recurrence, cosmetics and patient satisfaction.

A Randomised Comparison of Two Laser Iridotomy Techniques in Patients of Primary Angle Closure Disease with Absent Iris Crypts

Purpose: Patients with absent iris crypts are the most challenging cases for performing laser peripheral iridotomy. This study was conducted on patients of primary angle closure disease belonging to this group to find out the difference in the quantum of energy and number of attempts required to achieve optimum peripheral iridotomy by sequentially using double frequency Nd:YAG and Nd:YAG laser versus Nd:YAG laser alone. Methods: Forty eyes of 40 patients of 35 years or more, with primary angle closure disease and absent iris crypts, in whom laser peripheral iridotomy (LPI) was indicated, were prospectively randomized into two groups. Patients in group one sequentially underwent double frequency Nd:YAG & Nd:YAG laser and group two underwent Nd:YAG laser alone. Follow up was done one hour, three hours, one day and one week post laser. Any rise of IOP of > 8 mmHg from base line or an absolute figure of 30 mmHg at any visit was considered significant. Post laser topical loteprednol etabonate 4 times per day for one week and pilocarpine nitrate 2% eye drops twice a day for five days were used in all cases. Statistical testing was conducted with the statistical package for the social science system (SPSS) version 17.0. Results: Group one had 3 male and 16 female patients whereas group two had 9 and 12 male and female patients respectively. Nd:YAG energy required in group one (n=19) was 48.79 ± 19.41 mJ and in group two (n=21) was 88.81 ± 37.36 mJ (p=<0.001). In group one, an optimum LPI could be achieved in single sitting in 18 out of 19 patients. In group two, out of a total of 21 patients, 8 (38.1%) required one sitting, 11 (52.4%) required two sittings and two (9.5%) required three sittings to achieve patent PI. The difference was highly significant (p<0.001). The reasons for multiple sittings included haemorrhage (n=8) and iris chafing (n=8). Conclusion: Sequential use of the double frequency Nd:YAG followed by Nd:YAG laser is superior to YAG laser alone in terms of required energy and number of sittings for the purpose of doing laser peripheral iridotomy among patients with absent iris crypts.

Potential Use of Cyclodextrin Complexes for Enhanced Stability, Anti-inflammatory Efficacy, and Ocular Bioavailability of Loteprednol Etabonate.

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 6months. 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.

PLGA nanoparticles for ocular delivery of loteprednol etabonate: a corneal penetration study

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.

Pterígio e sua abordagem cirúrgica com membrana amniótica

A patogênese do Pterígio está fortemente relacionada à exposição à luz ultravioleta, ressecamento, inflamação crônica e exposição a vento e poeira; substâncias irritantes também são consideradas fatores predisponentes na histopatologia na degeneração elástica do colágeno estromal e tecido fibrovascular subepitelial.A prevalência aumenta progressivamente com a proximidade à linha do equador.O método de correção cirúrgica considerado pela comunidade médica e pela literatura é o transplante de conjuntiva; entretanto exponho aqui minha experiência e de nossa equipe em aproximadamente 6.000 casos desde 1996, realizados com membrana amniótica. As vantagens na utilização desse método são em primeiro lugar a economia do tecido conjuntival do paciente, o mesmo índice de recidiva do transplante livre de conjuntiva ± 4%, aspecto estético igual ou melhor e a obtenção infinda desse tecido. A técnica utilizada nos últimos quatro anos inclui anestesia subtenoniana com Levobupivacaina 0,50% 5mg/mL, a ampla excisão do corpo do pterígio, a retirada da cabeça por dissecção ou arrancamento, uso de mitomicina 0,02 por 2 minutos e lavado intensamente com soro e uso da cola de fibrina para posicionamento do retalho de membrana amniótica.Casos de Pterígio primário, recidivados, ou extensos assim como os pterígios duplos nasal e temporal que requerem muito tecido, são facilmente reparados com retalhos de membrana amniótica e não poderiam ser feitos com retalhos conjuntivais pela extensão de tecido requerida.Os retalhos de membrana amniótica são preparados a partir de placentas obtidas por parto cesáreo, em pacientes com pré-natal completo, com exames para hepatites, sífilis e HIV e colocados em retalhos de papel de filtro e estocados em geladeira embebidos em solução de antibiótico e glicerina (100%) e hidratados com soro ou ringer no momento da cirurgia. O posicionamento correto da membrana amniótica é com a parte estromal voltada para a superfície ocular (enxerto) e essa servirá como membrana basal ao crescimento de conjuntiva que apresenta estereótipo indistinguível da conjuntiva normal.O pós-operatório inclui curativo oclusivo por 3 dias com 2 trocas diárias com colírio e pomada de antibiótico e corticoide. Após os 3 dias é receitado colírio de Hialuronato de sódio 2mg/mL de 2 em 2 horas, mais, colírio de associação antibiótico, mais, corticosteroide 4 vezes ao dia por 1 semana.É sabido que há polêmicas em vários itens sobre cirurgia de pterígeo – entre eles:Anestesia: alguns sugerem anestesia retrobulbar, outros peribulbar, outros subtenoniana (nossa preferência), subconjuntival, somente tópica e há até os que realizam cirurgia sob anestesia geral. A experiência, após anos de testes nas várias modalidades, mostrou que a anestesia subtenoniana com Levobupivacaína sem conservante 3 ml proporciona um pouco mais de conforto nesse pós operatório de sintomatologia tão intensa.Pós operatório: no pós operatório utilizo para analgesia anti-inflamatório não hormonal), associado à Tylex®, Dipirona gotas (até de 4/4 horas).Cola ou Sutura: Polêmica também é a escolha de cola ou sutura na fixação do retalho, seja conjuntival, seja de membrana amniótica. Minha experiência com cola data de 3 anos e utilizamos apenas cola, com preferência a Tissucol® (Baxter®) – que tem funcionado melhor. Anteriormente usávamos sutura com nylon 10.0. Alguns colegas associam alguns pontos de sutura à cola (4 pontos), mas a experiência com cola e membrana mostrou que não é necessário suturar.Membrana amniótica: Amnion ou porção interna das membranas placentarias consiste de uma membrana basal e matriz estromal avascular. A composição da membrana basal é semelhante à da conjuntiva, e é considerada como substrato ideal para garantir o crescimento de tecido conjuntival e suporte de um retalho conjuntival. Nos casos nos quais as diversas recidivas impõem um tratamento cirúrgico com todos os recursos a membrana amniótica mostrou ser de grande valia.A escolha desse tecido na reconstrução da conjuntiva em Exérese de Pterígeo e em outras lesões conjuntivais deve-se às propriedades da membrana facilitando a epitelização, mantendo fenótipo epitelial idêntico ao da conjuntiva e ao mesmo tempo reduzindo inflamação, vascularização e cicatrização.Também é importante ressaltar a facilidade de obtenção desse tecido e a preservação da conjuntiva para outros procedimentos futuros como recobrimento conjuntival, cirurgias de glaucoma, entre outros, especialmente o excelente resultado estético e funcional assim como o baixo índice de recidiva.Nas figuras 1 a 8 ilustra-se, caso de Pterígeo extenso que cobria a córnea em olho direito e bilateral, porém menos extenso no olho esquerdo e seu resultado final.

Effect on Gel Formation Time of Adding Topical Ophthalmic Medications to ReSure Sealant, an In Situ Hydrogel.

The purpose of this study was to describe the gel formation times of ReSure(®) Sealant, an in situ hydrogel approved to seal cataract surgery incisions, when commercially available topical medications are mixed with the sealant. In this experimental laboratory study, the commercial product, ReSure Sealant, was used as per the product insert. Two drops of diluent were mixed with the polymer and time to gel formation was measured. Following this, various commercial antibiotic, nonsteroidal anti-inflammatory drug and steroid drops were used in substitution of one of the drops of the diluent. Combinations of 2 medications were also tested. Each condition was performed in triplicate and the mean gel time was calculated. The addition of bromfenac slightly reduced mean gel time from 19 s (ReSure alone) to 13 s. All other medications, including moxifloxacin, gatifloxacin, ofloxacin, ciprofloxacin, loteprednol etabonate, prednisolone acetate, dexamethasone, ketorolac, and nepafenac, increased mean gel time, ranging from 49 s to >120 s. The addition of bromfenac to moxifloxacin, ofloxacin, or gatifloxacin reduced their mean gel times from ≥105 s to 18-29 s. Certain medications, specifically bromfenac, may not substantially alter time to gel formation of ReSure Sealant when added to the hydrogel. In fact, bromfenac added to moxifloxacin, ofloxacin, or gatifloxacin reduced gel formation time to acceptable levels. All other medications and combinations of medications added to ReSure Sealant produced unacceptably long gel times to be used routinely. Clinical studies may be considered based on these results to assess the safety and efficacy of this strategy.

Simultaneous Estimation of Loteprednol Etabonate and Gatifloxacin in Pharmaceutical Dosage Form by UHPLC Method

A reverse phase ultra-high performance liquid chromatography (RP-UHPLC) method was developed and validated for the simultaneous estimation of Loteprednoletabonate (LOTE) and Gatifloxacin (GAT) in pharmaceuticaldosage form. The separation was carried on zorbax eclipse plus column C18 (4.6 × 50 mm, 1.8 μ particle size) column with mobile phase (pH 6.0 withtriethylamine) containing Acetonitrile, Methanol and 0.02M potassiumdihydrogen phosphate in the ratio of 40:30:30 v/v/v with a flow rate of 0.7 mL/min and UV detection at 272 nm. The linearity was found to be in range of 15.34-46.03 μg/mL (R 2 = 0.999) and 24.94-74.81 μg/mL (R 2 = 0.999) for GAT and LOTE respectively. The method has shown good, consistent recoveries for GAT 98.88-101.24% and LOTE 98.42 - 100.94% respectively. The method was found to be accurate, precise, specific,robust and linear for the determination of GAT and LOTE in pharmaceutical dosage form.

Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure.

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.