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Eye & Contact Lens Jun 2023To describe the labeling, packaging practices, and characteristics of compounded 0.01% ophthalmic atropine. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To describe the labeling, packaging practices, and characteristics of compounded 0.01% ophthalmic atropine.
METHODS
A convenience sample of parents of children who had previously been prescribed low-concentration atropine for myopia management were randomized to obtain 0.01% atropine ophthalmic solution from one of nine compounding pharmacies. The products were analyzed for various important quality attributes. The main outcomes were labeling practices, concentration of atropine and degradant product tropic acid, pH, osmolarity, viscosity, and excipients in 0.01% atropine samples obtained from nine US compounding pharmacies.
RESULTS
Twenty-four samples from nine pharmacies were analyzed. The median bottle size was 10 mL (range 3.5-15 mL), and eight of nine pharmacies used clear plastic bottles. Storage recommendations varied and were evenly split between refrigeration (33%), room temperature (33%), and cool, dark, dry location (33%). Beyond use dates ranged from 7 to 175 days (median, 91 days). Median pH of samples was 7.1 (range, 5.5-7.8). Median measured concentration relative to the prescribed concentration was 93.3% (70.4%-104.1%). One quarter of samples were under the 90% minimum target concentration of 0.01%.
CONCLUSIONS
An inconsistent and wide variety of formulation and labeling practices exist for compounding 0.01% atropine prescribed to slow pediatric myopia progression.
Topics: Humans; Child; Atropine; Drug Compounding; Myopia; Ophthalmic Solutions
PubMed: 37022143
DOI: 10.1097/ICL.0000000000000990 -
Clinical & Experimental Optometry Sep 2017Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the... (Review)
Review
Contact lenses as a means to deliver pharmaceuticals to the eye have seen a significant increase in research interest in the past few years. This review will detail the in vitro experiments which have investigated use of these contact lenses in the context of the desired pharmacological treatment goals in the management of infectious, inflammatory, allergic and glaucomatous diseases of the eye. The techniques researchers have employed to modify and tailor drug release rates from these materials, including the use of vitamin E diffusion barriers, modified ionicity, molecular imprinting and incorporation of drug reservoirs, will be discussed, as well as their impact on drug release kinetics. Finally, the demonstration of the feasibility of these materials when applied in vivo in animal models as well as in humans with and without disease will be presented and their results discussed relating to their implications for the future of the field.
Topics: Contact Lenses, Hydrophilic; Drug Delivery Systems; Humans; Ophthalmic Solutions; Pharmaceutical Preparations
PubMed: 28940532
DOI: 10.1111/cxo.12592 -
Recent Patents on Drug Delivery &... 2014Nanoformulations (NF) are widely explored as potential alternatives for traditional ophthalmic formulation approaches. The effective treatment of ocular diseases using... (Review)
Review
Nanoformulations (NF) are widely explored as potential alternatives for traditional ophthalmic formulation approaches. The effective treatment of ocular diseases using conventional eye drops is often hampered by factors such as: physiological barriers, rapid elimination, protein binding, and enzymatic drug degradation. Combined, these factors are known to contribute to reduced ocular residence time and poor bioavailability. Recent research studies demonstrated that NF can significantly enhance the therapeutic efficacy and bioavailability of ocular drugs, compared to the established ophthalmic drug delivery strategies. The research studies resulted in a number of patent inventions, reporting a significant increase in therapeutic efficacy for various chronic ocular disease states of both the anterior and posterior ocular segments. This article reviews these patent disclosures in detail and emphasizes the therapeutic advantages conferred by the following nanoformulation approaches: Calcium Phosphate (CaP) nanoparticles, Liposomes, Nanoemulsions, Nanomicelles, and Hydrogels. The nanoformulation approaches were shown to enhance the ocular bioavailability by reducing the drugprotein binding, increasing the corneal resident time, enhancing the drug permeability and providing a sustained drug release. Further, the article discusses United States Food and Drug Administration (USFDA) approved ocular drugs employing nanotechnology and future developments. It should be noted that, despite the potential therapeutic promise demonstrated by nanotechnology for ocular drug delivery, the bench to bed transition from patent inventions to marketed drug products has been insignificant. Majority of the discussed technologies are still in development and testing phase for commercial viability. Further, studies are in progress to assess ocular tolerance and nanotoxicity for prolonged use of NF.
Topics: Administration, Ophthalmic; Animals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Humans; Nanoparticles; Ophthalmic Solutions; Patents as Topic
PubMed: 25262835
DOI: 10.2174/1872211308666140926112000 -
Journal of Ocular Pharmacology and... 2019Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis,... (Review)
Review
Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis, conjunctivitis, and blepharitis. These classes of drugs have come to occupy an important niche in ophthalmic antifungal therapy due to their broad spectrum of activity against a variety of filamentous and yeast-like fungi. Natamycin suspension (Natacyn), a polyene antifungal drug, is currently the only US FDA-approved formulation for treating ophthalmic fungal infections, whereas the other polyene and azole antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole, and posaconazole are routinely used off-label in the clinical setting. Despite potent antifungal activity, the clinical utility of these agents in ophthalmic infections has been challenged by their physicochemical properties, the unique ocular anatomy and physiology, selective antifungal activity, ocular and systemic toxicity, emergence of resistance and cross-resistance, and absence of reliable techniques for developing a robust in vitro-in vivo correlation. This review discusses the aforementioned challenges and the common approaches undertaken to circumnavigate the difficulties associated with the polyene- and azole-based pharmacotherapy of ophthalmic fungal infections.
Topics: Animals; Antifungal Agents; Azoles; Eye Infections, Fungal; Humans; Microbial Sensitivity Tests; Ophthalmic Solutions; Polyenes
PubMed: 30481082
DOI: 10.1089/jop.2018.0089 -
International Journal For Parasitology.... Aug 2021The main corneal infections reported worldwide are caused by bacteria and viruses but, recently, the number of Acanthamoeba keratitis (AK) cases has increased....
The main corneal infections reported worldwide are caused by bacteria and viruses but, recently, the number of Acanthamoeba keratitis (AK) cases has increased. Acanthamoeba genus is an opportunistic free living protozoa widely distributed in environmental and clinical sources, with two life-cycle stages: the trophozoite and the cyst. AK presents as primary symptoms eye redness, epithelial defects, photophobia and intense pain. An early diagnosis and an effective treatment are crucial to avoid blindness or eye removal but, so far, there is no established treatment to this corneal infection. Diverse research studies have reported the efficacy of commercialized eye drops and ophthalmic solutions against the two life cycle stages of Acanthamoeba strains, that usually present preservatives such as Propylene Glycol of Benzalkonium chloride (BAK). These compounds present toxic effects in corneal cells, favouring the inflammatory response in the so sensitive eye tissue. In the present work we have evaluated the efficacy of nine proprietary ophthalmic solutions with and without preservatives (ASDA Dry Eyes Eyedrops, Miren®, ODM5®, Ectodol®, Systane® Complete, Ocudox®, Matrix Ocular®, Alins® and Coqun®) against the two life cycle stages of three Acanthamoeba strains. Our work has demonstrated the high anti-Acanthamoeba activity of Matrix Ocular®, which induces the programmed cell death mechanisms in Acanthamoeba spp. trophozoites. The high efficacy and the absence of ocular toxic effects of Matrix Ocular®, evidences the use of the Arabinogalactan derivatives as a new source of anti-AK compounds.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Amebicides; Galactans; Humans; Ophthalmic Solutions
PubMed: 33895610
DOI: 10.1016/j.ijpddr.2021.04.005 -
Advances in Therapy Aug 2023Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine.
METHODS
This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics.
RESULTS
Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC.
CONCLUSION
RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC.
TRIAL REGISTRATION
Japan Registry of Clinical Trials; Registration No. jRCT2080225220.
Topics: Male; Adult; Humans; Brimonidine Tartrate; Glaucoma, Open-Angle; Ocular Hypertension; Prospective Studies; Hyperemia; Endothelial Cells; Intraocular Pressure; Ophthalmic Solutions; Antihypertensive Agents; Quinoxalines
PubMed: 37330927
DOI: 10.1007/s12325-023-02534-w -
Advances in Therapy Aug 2022DE-089C is a newly developed long-acting formulation of diquafosol ophthalmic solution with less frequent administration (three times daily) than the currently approved... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
DE-089C is a newly developed long-acting formulation of diquafosol ophthalmic solution with less frequent administration (three times daily) than the currently approved and clinically used diquafosol ophthalmic solution (six times daily), hereinafter referred to as DQS. DE-089C is desirable for achieving better patient adherence in clinical practice for dry eye therapy. The objective of this study was to confirm the efficacy and safety of DE-089C in patients with dry eye compared to placebo.
METHODS
This randomized, multicenter, double-masked, placebo-controlled, parallel-group phase 3 study was conducted in Japan. Patients with aqueous-deficient dry eye satisfying Schirmer's test I results ≤ 5 mm/5 min were included. A total of 337 patients with dry eye were randomized in an equal ratio to treatment with DE-089C or placebo ophthalmic solution, three times daily for 4 weeks. The primary endpoint for efficacy was change in fluorescein corneal staining score from baseline to week 4. The incidence of adverse drug reactions was investigated for safety evaluation.
RESULTS
The background characteristics of patients in the two groups were similar. Primary endpoint of change in fluorescein corneal staining score at week 4 in the DE-089C group was significantly improved compared with the placebo group (least squares mean difference - 0.51, 95% CI - 0.754 to - 0.269, P < 0.0001). The secondary endpoint of the Lissamine green conjunctival staining score was also significantly improved in the DE-089C group compared to that in the placebo group, while other secondary endpoints were not achieved in this study. Commonly (incidence ≥ 1%) reported adverse drug reactions in the DE-089C group were eye irritation (3.6%) and eye discharge (1.8%) with mild severity, and the incidences of these two events were not higher than those in previous clinical studies on DQS.
CONCLUSION
The efficacy and safety of DE-089C administered three times daily at half the dosage of DQS in patients with dry eye were confirmed in this study.
TRIAL REGISTRATION
Japan Pharmaceutical Information Center ID, JapicCTI-205177.
Topics: Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Dry Eye Syndromes; Fluorescein; Humans; Ophthalmic Solutions; Polyphosphates; Tears; Treatment Outcome; Uracil Nucleotides
PubMed: 35716319
DOI: 10.1007/s12325-022-02194-2 -
Advances in Therapy Sep 2023This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1%... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.
INTRODUCTION
This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues.
METHODS
A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews.
RESULTS
BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation.
CONCLUSION
As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.
TRIAL REGISTRATION NUMBER
jRCTs051190125.
Topics: Humans; Timolol; Glaucoma, Open-Angle; Cross-Over Studies; Antihypertensive Agents; Ophthalmic Solutions; Brimonidine Tartrate; Intraocular Pressure; Prostaglandins, Synthetic; Drug Combinations
PubMed: 37452961
DOI: 10.1007/s12325-023-02589-9 -
Revista Brasileira de Psiquiatria (Sao... Nov 2022Over the past 15 years, the increasing nonmedical use of tropicamide ophthalmic drops has been reported in Europe, coinciding with an increase in opioid addiction and... (Review)
Review
Over the past 15 years, the increasing nonmedical use of tropicamide ophthalmic drops has been reported in Europe, coinciding with an increase in opioid addiction and drug-related mortality. Although tropicamide is generally known as a cheap alternative to heroin in Eastern Europe, it still appears to be a relatively new phenomenon that has arisen over the last decade. A narrative review was conducted of all the relevant sources published in more than five countries between January 1, 1975 and January 10, 2021. For bibliographic accuracy, the materials published in Russian and Italian were professionally translated to English. During the preparation of this report, we were able to interview five Russian-speaking patients who injected tropicamide in the past and we discuss another case of intravenous tropicamide use. This review was acknowledged by the institutional review board of the University of Missouri-Kansas City. All patients interviewed at the Unica Medical Center consented for their clinical information to be reported in a medical publication. We analyzed data from 50+ various sources and covered a variety of drug-related issues, including information on the extent, patterns, and trends in tropicamide use, its health consequences, and other clinical findings. The information provided in this article may help providers better detect tropicamide abuse and incorporate new rehabilitation strategies into the management of these patients.
Topics: Humans; Tropicamide; Ophthalmic Solutions; Europe; Italy
PubMed: 35739063
DOI: 10.47626/1516-4446-2021-2446 -
Therapeutic Delivery Dec 2014Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives... (Review)
Review
Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long-term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient's lifetime.
Topics: Absorbable Implants; Biological Availability; Contact Lenses; Drug Delivery Systems; Eye Diseases; Humans; Intravitreal Injections; Nanoparticles; Ointments; Ophthalmic Solutions; Solubility; Tissue Adhesives; Viscosity
PubMed: 25531930
DOI: 10.4155/tde.14.75