Brimonidine Research Articles

Ocular Distribution of Brimonidine and Brinzolamide after Topical Instillation of a 0.1% Brimonidine Tartrate and 1% Brinzolamide Fixed-Combination Ophthalmic Suspension: An Interventional Study.

To evaluate the concentrations of brimonidine and brinzolamide in the vitreous and aqueous humor after instillation of a 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. The present investigation involved patients with macular holes or idiopathic epiretinal membranes who were planning to undergo vitrectomy. One week prior to surgery, the patients received twice-daily topical treatment with 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. Before vitrectomy, vitreous and aqueous humor samples were collected, and the mean concentrations of brimonidine and brinzolamide were determined through liquid chromatography-tandem spectrometry. Ten eyes (nine phakic and one pseudophakic eyes; 10 patients) were examined. The concentration of brimonidine in vitreous and aqueous humor samples was 5.02 ± 2.24 and 559 ± 670 nM, respectively. The concentration of brimonidine in the vitreous humor, which is needed to activate α2 receptors, was >2 nM in all patients. The concentration of brinzolamide was 8.96 ± 4.65 and 1100 ± 813 nM, respectively. However, there was no significant correlation between the concentrations of brimonidine in the vitreous and aqueous humor samples. Sufficient concentrations of brimonidine were detected in all vitreous samples. The dissociated correlation of the drug concentrations between aqueous and vitreous humors implies the possibility of another pathway to vitreous humor, different from the pathway to aqueous humor.

Topical brimonidine for the management of facial erythema in rosacea: a histological, histometric, and immunohistochemical study.

Facial erythema in rosacea is a troublesome embarrassing presentation with limited options of treatment. Daily brimonidine gel was shown to be an effective modality of treatment. Being unavailable in Egypt and the scarcity of objective evaluation of its therapeutic effect motivated the search for other alternatives. To evaluate the use and effectiveness of topical brimonidine eye drops for the management of facial erythema in rosacea with the aid of objective assessment. The study was conducted on 10 rosacea patients presented with facial erythema. Brimonidine tartrate eye drops 0.2% were applied twice daily for 3 months on areas of red facial skin. Punch biopsies were obtained before and after 3 months of treatment. Routine hematoxylin and eosin (H&E) staining as well as CD34 immunohistochemical staining were performed for all biopsies. Sections were examined to detect the changes in the count and the surface area of blood vessels. Evaluation of clinical results showed good improvement of facial redness at the end of treatment (55-75%). Only 10% of subjects expressed rebound erythema. H&E and CD34 stained sections showed an increased count of dilated dermal blood vessels, which decreased significantly after treatment in count and surface area (P = 0.005, and P = 0.004, respectively). Topical brimonidine eye drops proved to be effective in managing facial erythema in rosacea, providing an available and cheaper alternative to brimonidine gel. The study improved the subjective evaluation in the context of objective assessment of treatment efficacy.

Effects of brimonidine tartrate 0.2 and 0.15% ophthalmic solution on the static and dynamic pupil characteristics.

To investigate the differences between 0.2 and 0.15% brimonidine tartrate eye drops for anti-mydriatic effects and the optical quality under different light conditions. This prospective study involved 80 consecutive high myopia patients undergoing implantation of a V4c ICL. The patients were randomly instilled with brimonidine 0.2 and 0.15% 2 weeks postoperatively. Visual quality, pupil center, pupil size, and refraction under different light conditions were measured before and 0.5 h after brimonidine administration. A symptom questionnaire was also evaluated. There was no statistical difference in the static and dynamic pupil diameters and velocity after LS between the two groups (p > 0.05). The 0.2% group had significant changes in pupil center before and after treatment, while there was no obvious movement of the 0.15% group under all illumination condition (p > 0.05). The OSI after treatment of the 0.15% group was lower than that of 0.2% group (p = 0.012). The PVA9% and PVA100% of the 0.15% group was higher than that of 0.2% group in the dark (p = 0.009, p = 0.012). The HOA RMS of the 0.15% group was lower than that of 0.2% group (p = 0.016). The QIRC score in the 0.15% group was significantly higher than that in the 0.2% group (p = 0.043). 0.15 and 0.2% brimonidine tartrate eye drops had similar anti-mydriatic ability, while 0.15% group had better visual quality than 0.2% concentration, and hardly introduced pupil shift. 0.15% brimonidine tartrate eye drops may be more suitable for patients with nocturnal glare symptoms in the early postoperative period after ICL implantation.

RP-HPLC Method Development for Simultaneous Estimation of Brimonidine Tartrate and Timolol Maleate in Ophthalmic Preparation

Introduction: A simple, precise, rapid, and reproducible RP-HPLC method is developed for the simultaneous estimation of brimonidine tartrate and timolol maleate present in ophthalmic dosage forms.
 Method: Gradient RP-HPLC is carried out at 35℃ on column C18 (25 cm X 4.6 mm, 5 µm) with mobile phase a ACN and buffer (25 ml ACN & 475 ml buffer) and mobile phase B water and ACN (37.5 ml water & 212.5 ml ACN) at a flow rate of 1.2ml/min. detection is carried out using DAD detector at 248 nm. Parameter such as linearity, accuracy, precision, specificity, LOD, LOQ and robustness are studied as per ICH guidelines Q2 (R1). 
 Results: The linearity range of Brimonidine tartrate and Timolol maleate are 10-50 µg/ml and 4-20 µg/ml. The accuracy for both Brimonidine Tartrate and Timolol Maleate are in range of 100-101%. The RSD for Brimonidine Tartrate and Timolol Maleate are less than 2 for precision, specificity, robustness respectively. 
 Conclusion: This RP-HPLC method can be highly suitable for analysis of brimonidine tartrate and timolol maleate without interference in combined dosage form.

Bilateral Lipid Keratopathy in the Setting of Brimonidine Tartrate Use

Lipid keratopathy (LK) is a rare disease involving lipid deposition in the cornea resulting in corneal opacification. Primary LK can arise sporadically while secondary LK is seen in patients with a history of ocular trauma, medication exposure, infection, inflammation, or disorders resulting in derangements of lipid metabolism. Secondary LK is more common and occurs due to neovascularization. Use of precipitating medications should be considered in LK workup, particularly for patients in whom other etiologies have been ruled out. Brimonidine, an ocular hypotensive medication, can be associated with LK. We present a case of bilateral secondary LK in a patient with a history of prolonged brimonidine use, without additional contributing factors.

Comparisons of efficacy and safety between preserved and preservative-free brimonidine tartrate in glaucoma and ocular hypertension: a parallel-grouped, randomized trial

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.

To Evaluate the Efficiency with which Patients who have had ND-YAG Laser Capsulotomy may Reduce their Intraocular Pressure with a Predetermined Dosage of Brimonidine/Tart-Rate [0.2%] and Timalol/Maleate [0.5%

Background: The most prevalent type of glaucoma, known as primary open-angle glaucoma (POAG), is a major contributor to preventable blindness worldwide. Treating hypertensive ocular diseases, such as elevated intraocular pressure (IOP), may decrease the development and progression of (POAG). Objective: this study was to evaluate the efficiency with which patients who have had Nd-Yag laser capsulotomy may reduce their intraocular pressure with a predetermined dosage of brimonidine tartrate 0.2% and timalol maleate 0.5% Method: From January 2022 to January 2023, a prospective, randomized trial was conducted in the Department of Ophthalmology at KMC and KTH Peshawar. Sample size 100 patients who had undergone (Nd-Yag-laser capsulotomy) were enrolled in the study. After random selection, 50 patients were divided into two groups. Group 1 received (timolol maleate) [0.5%] BID daily and Group 2 received [0.5%] (timolol maleate) in a constant proportion in addition to (0.2%) brimonidine tartrate BID daily. Intraocular pressure (IOP) was assessed at the beginning, after one week, three weeks, and four weeks. The mean IOP at 4 weeks served as the major outcome indicator. Mean IOP at 1 week, 3 week, and 4 week intervals were included as secondary end measures. Descriptive statistics, the Student's t-test, and one-way ANOVA were used to analyse the data. Results: Mean IOP at baseline not significant with in two groups [P=0.36]. At one week, the mean IOP in the timolol group was 15.3 3.3 mmHg, compared to 13.1 2.9 mmHg in the timolol/brimonidine (P=0.001). At 3 weeks, (mean IOP) in the (timolol-group) was 14.4 3.1 mmHg, compared to 12.5 2.8 mmHg in the timolol/brimonidine group (p 0.001). At 4 weeks, the mean IOP in the timolol group was 13.8 3.1 mmHg, compared to 11.7 2.7 mmHg in the timolol/brimonidine group (p 0.001). Conclusion: this study show that persons who have had Nd-Yag laser capsulotomy benefit from a blending together timolol maleate [0.5%] and brimonidine tartrate [0.2%] to significantly reduce intraocular pressure (IOP). Keywords: Intraocular Pressure,ttimolol- maleate, brimoni-dine- tartrate, Nd-Yag Laser-Capsulotomy

Formulation and evaluation of ocular self-nanoemulsifying drug delivery system of brimonidine tartrate

The aim of the current study was to develop an ocular Self-nanoemulsifying drug delivery system (SNEDDS) loaded with Brimonidine tartrate (BRT) and evaluate its ex-vivo permeability. SNEDDS loaded with BRT were prepared by low energy method. Physicochemical properties, drug release, ex-vivo permeation, and toxicity studies were investigated. The BRT-loaded SNEDDS formulation was composed of Capmul MCM (Oil), Tween 80 (Surfactant), and Transcutol HP (Co-surfactant) and was optimized by Box-Behnken design. Optimized SNEDDS loaded with BRT had a droplet size of 118.3 nm, a PDI of 0.251, a pH of 6.34 ± 0.31, an osmolarity of 329 mosm/L after reconstitution with NaCl, and a viscosity was found to be 12.39 ± 2.31cP. The optimized SNEDDS loaded with BRT had excellent stability in the shelving period. The apparent permeability coefficient of optimized SNEDDS was found to be (7.078 ± 0.218 × 10−6 cm/s) when compared to the marketed formulation with (3.127 ± 0.173 × 10−6 cm/s). These results suggest that Brimonidine tartrate-loaded SNEDDS can be used as a promising nanocarrier for ocular drug delivery.

Development and validation of spectrophotometric methods for the simultaneous determination of Brimonidine Tartrate and Timolol Maleate in bulk and ophthalmic preparations

Development and validation of spectrophotometric methods for the simultaneous determination of Brimonidine Tartrate and Timolol Maleate in bulk and ophthalmic preparations

Sustained release of brimonidine from polydimethylsiloxane-coating silicone rubber implant to reduce intraocular pressure in glaucoma.

Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit's conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.

Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery

Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears.

Industry Update, October 2022.

Industry Update, October 2022.

Novel long-acting brimonidine tartrate loaded-PCL/PVP nanofibers for versatile biomedical applications: fabrication, characterization and antimicrobial evaluation.

The global state of antibiotic resistance highlights the necessity for new drugs that can treat a wide range of microbial infections. Drug repurposing has several advantages, including lower costs and improved safety compared to developing a new compound. The aim of the current study is to evaluate the repurposed antimicrobial activity of Brimonidine tartrate (BT), a well-known antiglaucoma drug, and to potentiate its antimicrobial effect by using electrospun nanofibrous scaffolds. BT-loaded nanofibers were fabricated in different drug concentrations (1.5, 3, 6, and 9%) via the electrospinning technique using two biopolymers (PCL and PVP). Then, the prepared nanofibers were characterized by SEM, XRD, FTIR, swelling ratio, and in vitro drug release. Afterward, the antimicrobial activities of the prepared nanofibers were investigated in vitro using different methods against several human pathogens and compared to the free BT. The results showed that all nanofibers were prepared successfully with a smooth surface. The diameters of nanofibers were reduced after loading of BT compared to the unloaded ones. In addition, scaffolds showed controlled-drug release profiles that were maintained for more than 7 days. The in vitro antimicrobial assessments revealed good activities for all scaffolds against most of the investigated human pathogens, particularly the one prepared with 9% BT which showed superiority in the antimicrobial effect over other scaffolds. To conclude, our findings proved the capability of nanofibers in loading BT and improving its repurposed antimicrobial efficacy. Therefore, it could be a promising carrier for BT to be used in combating numerous human pathogens.

Development and validation of spectrophotometric methods for the simultaneous determination of Brimonidine Tartrate and Timolol Maleate in bulk and ophthalmic preparations

Development and validation of spectrophotometric methods for the simultaneous determination of Brimonidine Tartrate and Timolol Maleate in bulk and ophthalmic preparations

Cationic liposomes as promising vehicles for timolol/brimonidine combination ocular delivery in glaucoma: formulation development and in vitro/in vivo evaluation.

Glaucoma is a chronic eye disease in which the pressure inside the eye increases and leads to damage to the optic nerve, and eventually causes blindness. In this disease, it is often necessary to use a multi-drug treatment system. There is a fixed combination of timolol maleate and brimonidine tartrate among the combination drugs in glaucoma treatment. Liposomes are one of the most important targeted drug delivery systems to eye tissue, which leads to improved drug permeability and durability in ocular tissue. In this study, thin layer hydration was used to make liposomal formulations containing timolol maleate (TM) and brimonidine tartrate (BT). After the necessary evaluations, one of the eight initial formulations was selected as an optimization formulation. Then, characteristics such as drug loading percentage, particle size, pH, zeta potential, and drug release were performed on the optimized formulation. The study of reducing intraocular pressure was performed on the optimized formulation. This study in total was performed on 18 rabbits in three groups. Hydroxypropyl methylcellulose (HPMC) polymer was injected into the anterior chamber to experimental induce glaucoma. The selected formulation was within the acceptable range of ocular products in terms of physical properties. HPMC polymer injection successfully induced glaucoma in the animal model, resulting in a 79% increase in intraocular pressure. The results showed that the liposomal formulation significantly reduced the intraocular pressure compared to the simple formulation of the aqueous solution, and both formulations were able to significantly reduce the intraocular pressure compared to the control group (P < 0.001). The results also showed that liposomal formulation has a therapeutic effect in reducing intraocular pressure. It seems that the selected liposomal formulation made by thin layer hydration can act as a suitable drug carrier to increase the effectiveness of the fixed combination of timolol maleate and brimonidine tartrate and be proposed as a new drug formulation for targeted and controlled drug delivery in the treatment of glaucoma.

Ocular surface assessment of preserved and preservative‐free brimonidine tartrate in glaucoma patients: A parallel‐grouped comparison trial

AbstractPurpose: To evaluate and compare the efficacy and safety of preservative‐free and preserved brimonidine tartrate 0.15% in open‐angle glaucoma and ocular hypertension.Methods: We conducted a multicenter (four institutions), randomized, investigator‐masked, parallel‐group clinical trial. A total of 60 eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open‐angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative‐free (n = 29) brimonidine groups. Enrolled eyes received three times daily monotherapy of brimonidine. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate at 12 weeks after the first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear‐film break‐up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events.Results: After 12 weeks, both preserved and preservative‐free groups showed similar amount of IOP reduction, corneal and conjunctival staining score, drug tolerance, and adherence rate. The preservative‐free group showed significantly better TBUT and higher patient satisfaction with regard to drug use and management. The reduction amount of systolic and diastolic blood pressures during 12 weeks were significantly lower in the preserved group than the preservative‐free group.Conclusions: Preservative‐free brimonidine tartrate showed comparable efficacy and safety with better corneal tear film stability and patient satisfaction compared to preserved brimonidine.

Controlling the Adsorption and Release of Ocular Drugs in Metal-Organic Frameworks: Effect of Polar Functional Groups.

A series of UiO-66 materials with different functional groups (-H, -NH2, and -NO2) have been evaluated for the adsorption and release of a common ocular drug such as brimonidine tartrate. UiO-66 samples were synthesized under solvothermal conditions and activated by solvent exchange with ethanol. Experimental results suggest that the incorporation of surface functionalities gives rise to the development of structural defects (missing linker defects) but without altering the basic topology of the UiO-66 framework. These defects improve the adsorption performance of the parent metal-organic framework (MOF), while the bulkier functionalities infer slower release kinetics, with the associated benefits for prolonged delivery of brimonidine. Among the evaluated MOFs, defective UiO-66-NO2 can be proposed as the most promising candidate due to the combination of a larger brimonidine volumetric uptake (680 mg/cm3), a prolonged delivery (period of up to 25 days), a small particle size, and a larger instability. Contrariwise, at high concentrations UiO-66-NO2 has higher toxicity toward human retinal pigment epithelium cells (ARPE-19) compared to the pure and NH2-functionalized UiO-66.

Inflammatory Cells and Lipid Deposits Detected by in Vivo Confocal Microscopy in Brimonidine Tartrate Ophthalmic Solution-Related Corneal Disorders: A Case Series

ABSTRACT We reviewed the medical charts of five patients diagnosed with brimonidine tartrate (BT)-related corneal disorders. A fan-shaped corneal opacity was present in four patients and limbal corneal infiltrations were present in one patient. In vivo confocal microscopy revealed dendritic cells and lipid deposits in the fan-shaped opacity as well as neutrophils in limbal infiltrations. BT instillation was discontinued and topical administration of a corticosteroid was initiated for all patients. The limbal infiltrations improved after BT discontinuation. Conversely, the fan-shaped opacity remained in all affected patients. After a fan-shaped opacity has developed in a patient with a BT-related corneal disorder, the lesion is difficult to resolve. However, limbal infiltrations respond well to treatment. Therefore, BT should be discontinued and anti-inflammatory treatment initiated before a fan-shaped opacity forms.

Preparation and Evolution of Soluble Ophthalmic Films of Brimonidine Tartrate In vitro

This study focuses on the treatment of Glaucoma with objectives overcomes certain disadvantages of Eye drops like the frequency of administration, drainage of medication by tear fluid, and greater therapeutic efficacy of drug (Brimonidine Tartrate) using ophthalmic films. The ophthalmic films of Brimonidine Tartrate were designed by solvent casting method containing PVA and PVP-k30 in different ratios as film formers, 20% v/v of PEG400 was added as plasticizer to 10 ml of distilled water. Films were evaluated for physicochemical characteristics such as folding endurance, drug content, thickness, pH of the surface, moisture absorption, moisture loss, and in vitro drug release. The drug release rates the prepared formulas didn’t take more than 4 hrs, the prepared formulas had acceptable physical properties. Increasing the ratios of used polymers prolonged the time of drug release from the matrix. Formula C6 which had the biggest ratio of polymers showed a controlled release within 4 hrs, however, formula C1 showed the least time of drug release in 1 hour. The drug release from most of the formulations was according to zero order pattern with n value in the range (0.5-1) indicating that drug release from matrices was mainly happened by swallowing and diffusion (non-Fickian pattern). Formula A6 by comparison with the rest of the prepared formulas showed slow release during 4 hrs

Brimonidine tartrate ophthalmic solution 0.025% for redness relief: an overview of safety and efficacy

ABSTRACT Introduction Ocular redness, or conjunctival hyperemia, is a common ophthalmic sign associated with reduced quality of life. For redness without apparent underlying pathology, topical ophthalmic decongestants have been widely used. Areas covered Brimonidine tartrate was approved in 2017 as a topical vasoconstrictor at a 0.025% concentration for relief of ocular redness. Since then, investigators have reported on efficacy and safety findings from studies evaluating low-dose brimonidine for reducing ocular redness. Expert opinion Brimonidine is highly selective for α2-adrenergic receptors. Clinical trials have so far shown that the drug in low doses significantly reduces ocular redness in comparison to vehicle for up to 8 hours. Brimonidine-treated eyes did not present side effects of other vasoconstrictors, such as hypotension, cardiac arrhythmia, or drowsiness. Ocular adverse events, such as allergic reactions and redness rebound, were also minimal. In this review, we examine in detail published literature on the mechanism of brimonidine tartrate and its efficacy and safety in relieving conjunctival hyperemia.