scholarly journals Formulation and Stability of Ataluren Eye Drop Oily Solution for Aniridia

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 7
Author(s):  
Celia Djayet ◽  
Dominique Bremond-Gignac ◽  
Justine Touchard ◽  
Philippe-Henri Secretan ◽  
Fabrice Vidal ◽  
...  
Keyword(s):  
Oxidative Degradation ◽  
Ophthalmic Solution ◽  
Eye Drops ◽  
Iris Defect ◽  
Drug Loss ◽  
Congenital Aniridia ◽  
Microbiological Stability ◽  
Foveal Hypoplasia ◽  
Preservative Free ◽  
Oily Solution

Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, corneal limbal insufficiency, glaucoma, cataract, optic nerve, and foveal hypoplasia. Ataluren eye drops aim to restore ocular surface PAX6 haploinsufficiency in aniridia-related keratopathy (ARK). However, there are currently no available forms of the ophthalmic solution. The objective of this study was to assess the physicochemical and microbiological stability of ataluren 1% eye drop in preservative-free low-density polyethylene (LDPE) bottle with an innovative insert that maintains sterility after opening. Because ataluren is a strongly lipophilic compound, the formulation is complex and involves a strategy based on co-solvents in an aqueous phase or an oily formulation capable of totally dissolving the active ingredient. The visual aspect, ataluren quantification by a stability-indicating chromatographic method, and microbiological sterility were analyzed. The oily formulation in castor oil and DMSO (10%) better protects ataluren hydrolysis and oxidative degradation and permits its complete solubilization. Throughout the 60 days period, the oily solution in the LDPE bottle remained clear without any precipitation or color modification, and no drug loss and no microbial development were detected. The demonstrated physical and microbiological stability of ataluren 1% eye drop formulation at 22–25 °C might facilitate clinical research in aniridia.

scholarly journals Preservative-free versus preserved latanoprost eye drops for reducing intraocular pressure: a non-inferiority phase III randomized, multi-center, single-blind, parallel-group controlled trial

2021 ◽  
Vol 9 (4) ◽  
Author(s):  
Panos Theodosiadis ◽  
Anastasios Konstas ◽  
Ioannis Halkiadakis ◽  
Vasiliki Dimera ◽  
Dimitrios Koufakis ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ocular Hypertension ◽  
Open Angle Glaucoma ◽  
Ophthalmic Solution ◽  
Phase Iii ◽  
Point Estimate ◽  
Eye Drops ◽  
Open Angle ◽  
Parallel Group ◽  
Preservative Free

Background: The aim of this study was to test the non-inferiority of preservative-free (PF) latanoprost 50 μg/mL multi-dose ophthalmic solution versus the marketed benzalkonium chloride (BAK)-preserved latanoprost 50 μg/mL ophthalmic solution in patients with open-angle glaucoma and patients with ocular hypertension. Methods: This was a prospective, national, randomized, multi-center, observer-blind, parallel-group controlled clinical trial. Patients were randomized to receive either PF or BAK-preserved latanoprost once daily for 12 weeks. The primary endpoint was the change in intraocular pressure (IOP) at 8:00 AM in the affected eye between the end of the treatment (week 12) and the baseline (week 0). Secondary measurements were taken at weeks 2 and 6, with IOP being recorded at 8:00 AM, 12:00 PM, and 4:00 PM. Results: A total of 158 patients were included in the per protocol (PP) population (77 in the PF latanoprost treatment arm and 81 patients in the BAK-preserved latanoprost treatment arm). PF latanoprost was non-inferior to BAK-preserved latanoprost in reducing IOP at 8:00 AM in the study eye from the baseline (week 0) to the end of the treatment (week 12). The point estimate of the between-treatment difference was 0.1 mmHg (95% confidence interval: -0.646, 0.847). Mean between-group differences in IOP reduction from the baseline to each of the secondary measurements were also similar between the two treatment arms. The two treatments were well tolerated and had comparable adverse event profiles. Conclusions: PF latanoprost was non-inferior to BAK-preserved latanoprost in reducing IOP in patients with open-angle glaucoma or ocular hypertension. Both treatments were well tolerated.

scholarly journals Non-inferiority evaluation of preservative-free latanoprost/timolol eye drops solution versus preserved latanoprost/timolol eye drops in patients with high intraocular pressure and open-angle glaucoma

2021 ◽  
Vol 9 (4) ◽  
Author(s):  
Panos Theodosiadis ◽  
Anastasios Konstas ◽  
Ioannis Halkiadakis ◽  
Vasiliki Dimera ◽  
Dimitrios Koufakis ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Open Angle Glaucoma ◽  
Ophthalmic Solution ◽  
Phase Iii ◽  
Point Estimate ◽  
Eye Drops ◽  
Open Angle ◽  
Local Tolerance ◽  
Safety Parameters ◽  
Preservative Free

Background: This study aimed to evaluate the non-inferiority and safety of a newly developed preservative-free (PF) multi-dose latanoprost/timolol ophthalmic solution, compared with the benzalkonium chloride (BAK)-preserved fixed combination, in patients with open-angle glaucoma and ocular hypertension.Methods: A Phase III randomized multi-center observer-blind parallel-group clinical trial was conducted. A total of 210 adult patients (aged over 18 years) were randomly treated with the PF- or the BAK-preserved latanoprost/timolol solution once daily in the affected eye(s) for 12 weeks. Follow-up visits were scheduled at weeks 2, 6, and 12; intraocular pressure (IOP) was recorded at 8:00 AM, 12:00 PM, and 4:00 PM. The primary efficacy endpoint to prove non-inferiority was the IOP change at 8:00 AM (± 1 hour) from the baseline to the end of treatment (week 12) in the studied eye. Safety parameters were also assessed.Results: In total, 196 patients completed the study. The pressure-lowering effect of the PF eye drops was comparable to that of the preserved formulation at all time points. Latanoprost/timolol PF formulation was non-inferior to the BAK-preserved solution as shown by the change in IOP from day 0 to week 12. The point estimate of the inter-treatment difference was 0.624 mmHg (95% CI: -0.094, 1.341). Both treatments were well-tolerated during the study, and they had similar adverse event profiles.Conclusions: PF-latanoprost/timolol combination was found to be non-inferior to the BAK-preserved formulation based on the efficacy at all times, with similar local tolerance.

scholarly journals Physical, chemical, and microbiological stability study of diluted atropine eye drops

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Jumpei Saito ◽  
Hitomi Imaizumi ◽  
Akimasa Yamatani
Keyword(s):  
Shelf Life ◽  
Package Insert ◽  
Ophthalmic Solution ◽  
Improve Patient Care ◽  
Stability Study ◽  
Eye Drops ◽  
Myopia Progression ◽  
Physical Chemical ◽  
Long Term Treatment ◽  
Microbiological Stability

Abstract Background Atropine eye drops are indicated for juvenile myopia progression, cycloplegia, amblyopia, and strabismus. According to the package insert, 10 mg/mL atropine eye drops must be diluted for pediatric patients to prevent systemic adverse effects. Compounding units in hospital pharmaceutical departments or community pharmacies are compelled to prepare this essential medication; however, validated atropine stability data is limited and the shelf life after preparation is extremely short. As it is a long-term treatment, a longer shelf life is necessary to improve patient care. This study aimed to demonstrate the physical, chemical, and microbiological stability of diluted atropine eye drops over a period of six months. Methods Preparation consists of dilution of a 10 mg/mL atropine solution (Nitten Atropine Ophthalmic Solution 1%; Nitten Pharmaceutical Co., Ltd.) in 0.9% NaCl to concentrations of 0.1, 1.0, 2.5, and 5.0 mg/mL, followed by a sterilizing filtration procedure and then an aseptic filling process of 5 mL in 5 mL polyethylene eyedropper bottles. The entire process is carried out in an overpressure isolator. All concentration products were kept for six months at 25 °C or 5 °C. Visual inspection was conducted and pH, osmolality, and atropine concentration were measured at day 0, day 14, day 28, and every month until six months. Atropine concentration was measured using liquid chromatography tandem mass spectrometry. The sterility was monitored using a method adapted from the Japanese Pharmacopoeia sterility assay. Results Atropine remained within ±5% of the target value in the six batches. Osmolality (285 mOsm/kg) as well as pH (5.88) were kept constant. No variations in solution characteristics (crystallization, discoloration) were noted. Sterility was maintained. Conclusions This study validated the physical, chemical, and microbiological stability of 0.1, 1.0, 2.5, and 5.0 mg/mL atropine sulfate eye drops conserved inside polyethylene eyedroppers for six months at 25 °C or 5 °C.

scholarly journals Comparison of ocular surface assessment and adherence between preserved and preservative-free latanoprost in glaucoma: a parallel-grouped randomized trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dai Woo Kim ◽  
Jonghoon Shin ◽  
Chang Kyu Lee ◽  
Myungjin Kim ◽  
Sohyeon Lee ◽  
...  
Keyword(s):  
Free Group ◽  
Ocular Surface ◽  
Open Angle Glaucoma ◽  
Drug Tolerance ◽  
Adherence Rate ◽  
Eye Drops ◽  
Ocular Surface Disease Index ◽  
Significant Difference ◽  
Surface Assessment ◽  
Preservative Free

AbstractGiven that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.

scholarly journals Better tolerance of preservative-free latanoprost compared to preserved glaucoma eye drops: the 12-month real-life FREE study

2018 ◽  
Vol Volume 12 ◽  
pp. 2399-2407 ◽  
Author(s):  
Mario A. Economou ◽  
Helene Laukeland ◽  
Iwona Grabska-Liberek ◽  
Jean-François Rouland
Keyword(s):  
Real Life ◽  
Eye Drops ◽  
Preservative Free

Treatment of persistent epithelial defects with single-dose autologous serum eye drops

2021 ◽  
pp. 112067212110483
Author(s):  
Selma Özbek-Uzman ◽  
Züleyha Yalnız-Akkaya ◽  
Evin Şingar Özdemir ◽  
Ayşe Burcu
Keyword(s):  
Single Dose ◽  
Healing Time ◽  
Autologous Serum ◽  
Eye Drops ◽  
Artificial Tears ◽  
Duration Of Treatment ◽  
The Mean ◽  
Preservative Free ◽  
Serum Eye Drops

Purpose: We aimed to investigate the efficacy and safety of single-dose autologous serum eye drops (ASEDs) for treatment of persistent corneal epithelial defects (PEDs). Methods: About 34 eyes of 26 patients treated from March 2016 to May 2020 with a single dose of ASEDs for PEDs that did not respond to conventional treatment were retrospectively evaluated. Patient demographics, predisposing factors, size, and duration of the PED, duration of treatment, and dosage of ASEDs, PED healing time, success rate of the ASED treatment, and follow-up time after the onset of ASED treatment were recorded. Autologous serum eye drops (20%) were prepared by diluting the serum with preservative-free artificial tears in single-dose vials. Vials were stored at −20°C and used daily after dissolving. Results: The mean patient age was 47.0 ± 18.5 years, and 13 (50%) of the patients were male. The most common indication for ASEDs was PED after keratoplasty. The mean duration of ASED treatment was 8.5 ± 6.3 months, and mean follow-up time was 22.8 ± 12.2 months. Autologous serum eye drop treatment was effective in 25 (73.5%) eyes and partially effective in 5 (14.7%) eyes. None of the eyes displayed complications related to the treatment. Conclusion: In patients with PED for whom conservative treatment is insufficient, ASEDs prepared by dilution with preservative-free artificial tears in single-dose vials and administered based on the daily use principle appear to be effective and safe.

scholarly journals Efficacy and Safety of Sodium Hyaluronate/chondroitin Sulfate Preservative-free Ophthalmic Solution in the Treatment of Dry Eye: A Clinical Trial

2020 ◽  
pp. 1-11
Author(s):  
Sandra Belalcázar-Rey ◽  
Valeria Sánchez Huerta ◽  
Juan C Ochoa-Tabares ◽  
Samuel Altamirano Vallejo ◽  
Abraham Soto-Gómez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Chondroitin Sulfate ◽  
Dry Eye ◽  
Sodium Hyaluronate ◽  
Ophthalmic Solution ◽  
Efficacy And Safety ◽  
Preservative Free

scholarly journals Efficacy of eye drops containing crosslinked hyaluronic acid and CoQ10 in restoring ocular health exposed to chlorinated water

2020 ◽  
Vol 30 (3) ◽  
pp. 430-438
Author(s):  
Costanza Tredici ◽  
Romina Fasciani ◽  
Antonio Villano ◽  
Gloria Gambini ◽  
Aldo Caporossi
Keyword(s):  
Hyaluronic Acid ◽  
Ocular Surface ◽  
Prolonged Exposure ◽  
Ophthalmic Solution ◽  
Disease Index ◽  
Eye Drops ◽  
Ocular Surface Disease Index ◽  
Vitamin E Tpgs ◽  
Grading Scale ◽  
Breakup Time

Purpose: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water. Methods: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5). Results: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (−3.00 s) ( p = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining ( p < 0.0001), Ocular Surface Disease Index ( p < 0.05), and visual analog scale ( p = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent. Conclusion: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL®, has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.

scholarly journals The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice

2020 ◽  
Vol 21 (10) ◽  
pp. 3516 ◽  
Author(s):  
Takashi Kojima ◽  
Taeko Nagata ◽  
Haruka Kudo ◽  
Wolfgang G. K. Müller-Lierheim ◽  
Gysbert-Botho van Setten ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Dry Eye ◽  
Ophthalmic Solution ◽  
Low Molecular Weight ◽  
Eye Drops ◽  
Office Work ◽  
Lissamine Green ◽  
Inflammatory Effect

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.

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