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Background: Brinzolamide (BRI) suspensions are used for the treatment of glaucoma; however, sufficient drug delivery to the target tissue after eye drop administration is hampered by poor solubility. To address this issue, we focused on nanocrystal technology, which is expected to improve the bioavailability of poor-solubility drugs, and investigated the effect of BRI nanocrystal formulations on corneal permeability and intraocular pressure (IOP)-reducing effect. Methods: BRI nanocrystal formulations were prepared by the wet-milling method with beads and additives. The particle size was measured by NANOSIGHT LM10, and the morphology was determined using a scanning probe microscope (SPM-9700) and a scanning electron microscope (SEM). Corneal permeability was evaluated in vitro using a Franz diffusion cell with rat corneas and in vivo using rabbits, and the IOP-reducing effect was investigated using a rabbit hypertensive model. Results: The particle size range for prepared BRI nanocrystal formulation was from 50 to 300 nm and the mean particle size was 135 ± 4 nm. The morphology was crystalline, and the nanoparticles were uniformly dispersed. In the corneal permeability study, BRI nanocrystallization exhibited higher corneal permeability than non-milled formulations. This result may be attributed to the increased solubility of BRI by nanocrystallization and the induction of energy-dependent endocytosis by the attachment of BRI nanoparticles to the cell membrane. Furthermore, the addition of tyloxapol to BRI nanocrystal formulation further improved the intraocular penetration of BRI and showed a stronger IOP-reducing effect than the commercial product. Conclusions: The combination of BRI nanocrystallization and tyloxapol is expected to be highly effective in glaucoma treatment and a useful tool for new ophthalmic drug delivery. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effectiveness of switching from the concomitant use of brinzolamide 1% (BZM) and brimonidine 0.1% (BMD) to a BZM/BMD fixed-dose combination (BBFC) for the reduction of corneal epithelial damage. Study Design: Retrospective cohort study. Methods: This study involved 52 eyes of 52 glaucoma patients (26 women, 26 men; mean age: 67.0 ± 14.0 years) followed for more than 3 months after being switched from concomitant BZM and BMD to BBFC. Superficial punctate keratitis (SPK) was assessed by fluorescein staining according to the National Eye Institute classification, with the cornea divided into 5 areas: center, superior, nasal, temporal, and inferior. SPK density was graded as 0 (no SPK), 1 (separate SPK), 2 (moderately dense SPK), and 3 (high SPK with overlapping lesions). SPK scores and intraocular pressure (IOP) at pre switching to BBFC (pre-BBFC) and at 3-months post switching to BBFC (post-BBFC) were then compared using the Wilcoxon signed-rank test. Results: At pre-BBFC and post-BBFC, respectively, mean IOP was 12.4 ± 2.5 and 12.4 ± 2.7 mmHg, thus illustrating no significant difference in IOP between pre and post switch (p = 0.924), and the mean SPK score for center, superior, nasal, temporal, and inferior was 0.06 ± 0.24, 0.04 ± 0.19, 0.52 ± 0.67, 0.15 ± 0.36, and 0.92 ± 0.74, and 0.04 ± 0.19, 0.02 ± 0.14, 0.37 ± 0.56, 0.04 ± 0.19, and 0.75 ± 0.62, thus clearly showing a significant reduction in SPK scores for the nasal, temporal, and inferior areas at post-BBFC compared to those at pre-BBFC (p < 0.05). Conclusion: Our findings reveal that compared with the concomitant use of BZM and BMD, BBFC is effective in reducing corneal epithelial damage. [ABSTRACT FROM AUTHOR]

Purpose: to conduct a comparative analysis of the clinical efficacy of a fixed combination of antihypertensive drugs: brinzolamide 1 % = timolol 0.5 % and dorzolamide 2 % = timolol 0.5 % for the prevention of intraocular hypertension in patients with silicone oil tamponade of the vitreal cavity.Patients and methods. The study was conducted in the Orenburg branch of S. Fyodorov Eye Microsurgery Federal State Institution during 2022. A retrospective analysis of case histories of 60 patients with retinal detachment and severe proliferative syndrome was carried out. All patients underwent subtotal vitrectomy. To prevent intraocular hypertension after tamponade of the vitreal cavity with silicone oil, patients were prescribed antihypertensive drugs: group 1 (n = 30) — a combination of brinzolamide 1 % = timolol 0.5 %; group 2 (n = 30) — dorzolamide 2 % = timolol 0.5 %. The therapeutic result was evaluated after 2 weeks, 1, 2 and 3 months. The observation included an ophthalmological examination, as well as a questionnaire to assess drug tolerance.Results. IOP after silicone oil tamponade and before the application of drugs had no statistically significant differences between the studied groups and amounted to 27.15 ± 3.56 mm Hg — in group 1 and 28.53 ± 5.99 mm Hg — in group 2. Both studied combinations provided a decrease in IOP, however, a more pronounced effect after 2 weeks of therapy with subsequent maintenance of a normal IOP level for 3 months was recorded in group 2 when using the dorzolamide / timolol combination, despite the appearance of minor discomfort during instillation. A decrease in IOP from baseline was found to be 43.5 % (p ≤ 0.01) with the combination dorzolamide/timolol and 33.3 % (p ≤ 0.01) for brinzolamide/timolol.Conclusion. The results of the study showed that both fixed combinations of drugs provide a decrease in IOP in patients after silicone tamponade, but the dorzolamide/timolol combination had a more pronounced therapeutic effect.

Abstract Background Brinzolamide (BRI) suspensions are used for the treatment of glaucoma; however, sufficient drug delivery to the target tissue after eye drop administration is hampered by poor solubility. To address this issue, we focused on nanocrystal technology, which is expected to improve the bioavailability of poor-solubility drugs, and investigated the effect of BRI nanocrystal formulations on corneal permeability and intraocular pressure (IOP)-reducing effect. Methods BRI nanocrystal formulations were prepared by the wet-milling method with beads and additives. The particle size was measured by NANOSIGHT LM10, and the morphology was determined using a scanning probe microscope (SPM-9700) and a scanning electron microscope (SEM). Corneal permeability was evaluated in vitro using a Franz diffusion cell with rat corneas and in vivo using rabbits, and the IOP-reducing effect was investigated using a rabbit hypertensive model. Results The particle size range for prepared BRI nanocrystal formulation was from 50 to 300 nm and the mean particle size was 135 ± 4 nm. The morphology was crystalline, and the nanoparticles were uniformly dispersed. In the corneal permeability study, BRI nanocrystallization exhibited higher corneal permeability than non-milled formulations. This result may be attributed to the increased solubility of BRI by nanocrystallization and the induction of energy-dependent endocytosis by the attachment of BRI nanoparticles to the cell membrane. Furthermore, the addition of tyloxapol to BRI nanocrystal formulation further improved the intraocular penetration of BRI and showed a stronger IOP-reducing effect than the commercial product. Conclusions The combination of BRI nanocrystallization and tyloxapol is expected to be highly effective in glaucoma treatment and a useful tool for new ophthalmic drug delivery.

Purpose: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). Design: Prospective, placebo-controlled, double-blind, cross-over study. Methods: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. Results: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture) . A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. Conclusions: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.

The aim of this work to study the feasibility of using phospholipid free vesicles with positive charge inducer in a slowly dissolving polymer ocular insert to successfully control intraocular pressure (IOP) for an extended period. Brinzolamide (BRNZ) was chosen as a model drug and a full factorial design was assembled to investigate the drug loading effect, ratio of cholesterol to fatty moiety and the type of the fatty moiety used on the vesicle size and entrapment efficiency. Linear regression models were constructed, and optimization of the formulation compositions yielded two formulae with palmitic acid as a negatively charged vesicles and cetrimide positively charged vesicles. Both formulae were studied in term of permeation efficiency through bovine corneal membranes. Positively charged vesicles although it didn't achieve the highest flux and cumulative amount permeated per unit surface area in the experiment time course, it achieved the highest retention of drug inside the corneal tissue, so it was chosen to be incorporated in a slowly dissolving polymer ocular insert. The insert was evaluated in term content, physical evaluation, and release properties. In vivo evaluation of the casted ocular inserts was conducted in male albino rabbits against market eye drop product and IOP readings were collected for 48 hours. The positively charged sterosomes containing BRNZ and formulated in polymer ocular inserts achieved extended control of IOP of the test animals compared to the market product. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker. Methods: Of these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan–Meier survival analysis. Results: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan–Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group. Conclusions: Concurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). Design: Prospective, placebo‑controlled, double‑blind, cross‑over study. Methods: Setting‑ A tertiary eye care center. Patients‑ Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention‑ Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure‑ Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. Results: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture). A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. Conclusions: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence. [ABSTRACT FROM AUTHOR]

Aim: This study aims to explore potential of transniosomes, a hybrid vesicular system, as ocular drug-delivery vehicle. Materials & methods: Thin-film hydration technique was used to fabricate brinzolamide-loaded transniosomes (BRZ-TN) and optimized using Box–Behnken design, further exhaustively characterized for physicochemical evaluations, deformability, drug release, permeation and preclinical evaluations for antiglaucoma activity. Results: The BRZ-TN showed ultradeformability (deformability index: 5.71), exhibiting sustained drug release without irritation (irritancy score: 0) and high permeability compared with the marketed formulation or free drug suspension. The extensive in vivo investigations affirmed effective targeted delivery of transniosomes, with brinzolamide reducing intraocular pressure potentially. Conclusion: Our findings anticipated that BRZ-TN is a promising therapeutic nanocarrier for effectively delivering cargo to targeted sites by crossing corneal barriers. Summary points Ocular drug delivery is an arduous task due to presence of several static and dynamic barriers. This research work presents the development and comprehensive investigation of a hyphenated colloidal system as a cutting-edge drug-delivery platform for efficient glaucoma treatment. Transniosomes are highly deformable hybrid vesicles possessing advantages of conventional vesicular systems and capable of improving corneal permeability. Brinzolamide-loaded transniosomes (BRZ-TN) were prepared and optimized using Box–Behnken design with a hypothesis to overcome aqueous insolubility of drug and promote corneal permeation. BRZ-TN showed a deformability index of 5.91, that is, highly elastic in nature, and proved its squeezability by passing through cornea efficiently, observed in confocal laser scanning microscope imaging. BRZ-TN exhibited permeation of 89.17 ± 4.39% with drug flux twice that of marketed formulation and apparent permeability of 0.044 in ex vivo permeation studies. Subsequent in vivo investigation carried out on New Zealand rabbits provides compelling evidence of enhanced therapeutic efficacy of BRZ-TN with 36% intraocular pressure reduction in 6 h. The developed BRZ-TN has the potential to serve as a superior alternative for glaucoma management. [ABSTRACT FROM AUTHOR]

Microemulsions (µEs) are more effective than conventional formulations for ophthalmic use due to their optical transparency, thermodynamic stability, structural flexibility and higher bioavailability. In addition, µE formulations can increase the water solubility of the drug and improve drug absorption in the eye. Herein, we report the development of three new biocompatible µE formulations containing an antihypertensive drug brinzolamide (BZD) and their evaluation for topical ocular administration. For this, Formulations A, B and C were optimized using an appropriate ratio of isopropyl myristate (IPM) as oil phase, water as aqueous phase and 2-propanol as co-surfactant, while Tween-80, Tween-20 and Tween-60 were selected as surfactant for each formulation, respectively. Preliminary, pseudoternary phase diagrams were delineated and then electrical conductivity and optical microscopy were used to establish optimal formulation for each µE to upheld the appropriate amount of BZD, i.e., 2.0 wt%, 2.0 wt%, and 1.0 wt% in formulation A, B and C, respectively. Dynamic light scattering demonstrated very fine monomodal assembly of BZD-µE nanodroplets (~50 nm), while FTIR analysis showed effective encapsulation of BZD into hydrophobic microenvironment with no observable chemical interaction between BZD and µE excipients, which was further verified by the peak-to-peak concomitant measurement of fluorescence. Further, invitro release of BZD-µE showed enhanced and persistent topical ocular administration (>99%) within 10 h demonstrating the appropriate formulation for topical instillation. [ABSTRACT FROM AUTHOR]

A sustainable reversed-phase chromatographic method has been developed and validated for the simultaneous determination of three active pharmaceutical ingredients, dorzolamide, brinzolamide, and timolol, used to treat glaucoma. The eco-friendly solvent isopropanol has been used as an organic mobile phase constituent. According to the Hansen space green solvent selection tool, isopropanol has a G score of 6.5, comparable to ethanol, which has a G score of 6.6. The mobile phase consists of isopropanol: aqueous sodium acetate buffer (0.1 M, pH 4.25) in the ratio of 10:90 (v/v). The flow rate was maintained at 1 mL/min. Dorzolamide and brinzolamide were detected at 254 nm, and timolol was detected at 295 nm. A high-purity silica with a polymeric C18 modification column (150 × 4.6 mm, 5 µm particle size) was used for this separation. The three compounds were eluted within 8 min. The method was validated according to ICH guidelines. The calibration curves were linear in the range of 20–70 µg/mL, 40–140 µg/mL, and 20–70 µg/mL for dorzolamide, brinzolamide, and timolol, respectively. The LODs were found to be 1.61 µg/mL, 1.60 µg/mL, and 3.16 µg/mL for dorzolamide, brinzolamide, and timolol, respectively. Good accuracy and precision were obtained for the three compounds. The greenness and whiteness of the method were indicated using the AGREE, ChlorTox, and RGB12 tools. [ABSTRACT FROM AUTHOR]

Purpose: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. Methods: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 μL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. Results: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. In conclusion: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma. [ABSTRACT FROM AUTHOR]

Glaucoma therapy aims at lowering intra-ocular pressure (IOP). Brinzolamide, a carbonic anhydrase inhibitor, is utilized as a second-line medication for treating ocular hypertension and primary open-angle glaucoma (POAG). The drug lowers the IOP making it a therapeutic agent against glaucoma, and due to its poor water solubility, is commercially available as Azopt®, a 1% ophthalmic suspension. Adverse effects such as blurred vision, ocular irritation, discomfort, and bitter taste are associated with the use of the marketed brinzolamide formulation. This study aims to test the feasibility of formulating and in vitro testing of brinzolamide-PLGA nanoparticles for improved toxicity profile. The nanoparticles were prepared by the oil-in-water (O/W) emulsion-solvent evaporation method. Particle size and zeta potential were determined by dynamic light scattering (DLS). The morphology of the nanoparticles was determined by scanning electron microscopy (SEM). Encapsulation of the drug was verified by high-performance liquid chromatography (HPLC) and the compatibility of the polymer and drug was verified by Fourier transform infrared (FTIR) spectroscopy. The in vitro drug release profile was assessed employing the dialysis method. Intracellular localization of the nanoparticles was assessed by confocal microscopy utilizing Rhodamine 123-loaded nanoparticles. Cytotoxicity of the formulation was assessed on Statens Seruminstitut Rabbit Cornea (SIRC) and transfected Human Corneal Epithelial (SV40 HCEC) cell lines. The particle size of the nanoparticle formulations ranged from 202.3 ± 2.9 nm to 483.1 ± 27.9 nm for blank nanoparticles, and 129.6 ± 1.5 nm to 350.9 ± 8.5 nm for drug-loaded nanoparticles. The polydispersity of the formulations ranged from 0.071 ± 0.032 to 0.247 ± 0.043 for blank nanoparticles, and 0.089 ± 0.028 to 0.158 ± 0.004 for drug-loaded nanoparticles. Drug loading and encapsulation efficiencies ranged from 7.42–15.84% and 38.93–74.18%, respectively. The in vitro drug release profile for the optimized formulation was biphasic, with a ~54% burst release for the initial 3 h, followed by a cumulative 85% and 99% released at 24 and 65 h, respectively. Uptake study showed nanoparticles(NPs) localization in the cytoplasm and around the nuclei of the cells. Brinzolamide-PLGA nanoparticles were successfully developed, characterized, and tested in vitro. Preliminary data show intracellular localization of the nanoparticles in the cytoplasm of SIRC and SV40 HCEC cells. The formulations appeared to be relatively non-cytotoxic to the cells. The research data from the study provided preliminary data for successful development and promising in vitro absorption efficacy for brinzolamide-loaded PLGA nanoparticle formulation. [ABSTRACT FROM AUTHOR]

This study outlines the development, optimization, and validation of a robust reverse-phase high-performance liquid chromatography (RP-HPLC) technique for the precise quantification of Brinzolamide in ophthalmic products, aligning International Council for Harmonization (ICH) guidelines. The method employed a Phenomenex (C18) (250x4.6mm) column with 5μm particle size as the stationary phase, a 1 mL/min flow rate for the mobile phase (composed of acetonitrile: water 35:65 v/v, pH adjusted to 3 with orthophosphoric acid), and detection at 254 nm. Under these conditions, Brinzolamide displayed Rt of 4.9 minutes. The validation process, following ICH standards, exhibited excellent linearity within the 5-30 μg/mL concentration range, with a limit of detection at 0.22 μg/mL and a limit of quantification at 0.67 μg/mL. Recovery rates from ophthalmic formulations fell between 98.3%-101.08%, indicating high accuracy. Accelerated stability assessments conducted over three months revealed content retention between 98.2%-100.9%, affirming the product's stability. Additionally, Brinzolamide withstood various stress conditions without interference in quantification, as the degradation products had distinct retention times from the pure drug, offering excellent resolution. In conclusion, this RP-HPLC method is suited for routine quality control analysis of Brinzolamide in commercial ophthalmic preparations, due to its specificity, accuracy, precision, and sensitivity, aligning perfectly with ICH guidelines. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is an optic neuropathy associated with characteristic structural damage to the optic nerve and associated visual dysfunction that may be caused by various pathological processes. A number of pharmacological agents are used to reduce the intraocular pressure (IOP), involving the usage of two or three medications concurrently. Literature is sparse regarding prescription patterns of antiglaucoma drugs, especially regarding variability in public sector vs private sector hospitals. Drug utilization studies can add insight for crafting rational, affordable, and ocular surface friendly prescriptions. Aim: This study assessed the prescription pattern in glaucoma patients of a public sector, tertiary care hospital vs a private sector tertiary care hospital. Materials and methods: In this retrospective study, pertinent data of diagnosed and labeled glaucoma patients were reviewed. Data collected included demographic details, type of glaucoma, number and nature of drugs prescribed, whether innovator or generic drugs were prescribed, if fixed-drug combinations (FDCs) and preservative-free formulations were prescribed. The prescription patterns between the two sectors were compared, as were the prescription patterns between primary open-angle glaucoma (POAG) and primary angle-closure disease (PACD). Results: A total of 336 prescriptions were evaluated (216 from public sector, group I; 120 from private sector, group II). Travoprost 0.004% was the most prescribed antiglaucoma medication in both group I (30.09%) and group II (38.33%). Brimonidine and brinzolamide (14.17%) was the most prescribed combination in group II, while Brimonidine with Timolol (7.87%) in group I. In group I, Timolol and Travoprost were the most prescribed medications for both PACD and POAG. Conclusion: This study showed that both public sector as well as private sector tertiary care centers prescribe antiglaucoma medications in tune with current principles of rational drug use. Preservative-free drugs were preferred in both the groups for better adherence. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits. Methods: A crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day's first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point. Results: There were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P < 0.01). Conclusion: BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF. [ABSTRACT FROM AUTHOR]

Multi-analyte determination techniques are favored over those that can only determine a single analyte at a time because they enable resource savings (cost, time, and solvents) and reduce generated waste and the number of samples required for analysis. This research presents a novel method for the simultaneous determination of brinzolamide (BRZ) and timolol maleate (TML) in pharmaceutical ophthalmic preparations using first-order derivative UV–Visible spectroscopy. The proposed approach is environmentally friendly and yet to be previously reported in the literature. In this approach, the peak amplitude of BRZ was quantified at the zero-crossing point of TML, i.e., 248.80 nm, whereas TML was determined by measuring absorbance at 297.60 nm. The developed method was validated according to the International Council for Harmonisation guidelines Q2(R1). The developed method was linear with excellent correlation coefficient values (R2 > 0.9998) in the range of 4 – 24 µg/ml for BRZ and 5 – 25 µg/ml for TML. The accuracy and precision results were within limits for both the analytes (%Relative standard deviation, RSD

Purpose: a comparative study of the efficacy and safety of the combination drug Brinzopt Plus and the original drug Azarga used as adjunctive therapy in patients with primary open-angle glaucoma (POAG) previously treated with latanoprost.Material and methods. 30 patients (42 eyes) with advanced and far advanced POAG were randomly divided into 2 groups of equal size. The patients of the main group (21 eyes) received Brinzopt Plus, those of the control group had the original drug Azarga, one instillation 2 times a day. The target points were intraocular pressure (IOP), visual acuity, perimetric indices (MD, PSD), mean retinal nerve fiber layer thickness, minimal neuroretinal rim width, retinal nerve fiber layer thickness in the macula, ganglion cell layer thickness in the macula, inner plexiform layer thickness, as well as the number of adverse events. The observation period was 12 weeks. IOP was measured at 4 and 12 weeks.Results. After 2 weeks, both groups showed a statistically significant decrease in IOP, which remained stable after 4 and 12 weeks. The average decrease in IOP in Brinzopt Plus recipients was 25% and revealed no statistically significant differences with the original drug at any control point. A positive dynamic of visual acuity, static perimetry and optical coherence tomography values, which showed no significant intergroup differences, was recorded. Among the adverse events, manifestations of mild local discomfort were recorded in 4 out of 15 patients of the main group and in 3 out of 15 patients of the control group. No serious or systemic adverse events were noted.Conclusion. Brinzopt Plus has an efficacy comparable to the original drug and a favorable safety profile.

Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04 nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10 h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6 h and trans-corneal permeability of 8.78 ± 0.14 cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Cataract if left untreated, can lead to complications such as lens induced glaucoma and permanent visual loss. The COVID-19 outbreak resulted in movement control orders causing closure and reduction of non-COVID hospital services resulting delayed appointment dates. This study described the side effects of delayed patient appointments due to COVID-19 pandemic. A 70-year-old man presented with right eye (RE) pain and redness. There was gradual reduction in RE vision over the last year but treatment was delayed due to pandemic. In examination, visual acuity on his RE was hand movement and left eye (LE) was 6/12 (ph6/12) and near vision of N5. The right pupil was mid-dilated, reacting sluggishly with presence of relative afferent pupillary defect. Intraocular pressure (IOP) on the RE was 54 mmHg and LE was 16 mmHg. Circumciliary injection of right conjunctiva with central corneal haziness was seen. The anterior chamber was deep with the presence of 3+ cells with whitish lens material at the pupillary axis. A Morgagnian cataract with phacodonesis was present. A diagnosis of lens induced glaucoma was made. Immediate reduction of IOP included topical and systemic medication and pain relief were instituted. Intracapsular cataract extraction with anterior vitrectomy and surgical peripheral iridectomy was performed. This highlights the late presentation of a patient with mature cataract during the COVID-19 pandemic. Patient awareness and education are essential in recognising the complications of mature cataract if it is presented later. A reminder of signs and symptoms of lens induced glaucoma should be conveyed to patient when appointment is delayed. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the ocular pharmacokinetic properties of intravitreally injected aflibercept in rabbits after using brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops. Methods: The right eye of 5 rabbits was topically administered 30 μL of brinzolamide and timolol maleate eye drops twice a day (q12h). The 2 eyes of each rabbit were injected with 1.0 mg (0.025 cc) of aflibercept on the 2nd day after instilling the eye drops. The intraocular pressure of the rabbits was measured before injection and sampling. The aqueous humor was drawn at 1, 3, 7, 14, 21, and 28 days. Aflibercept concentrations in aqueous humor and vitreous humor (28 days) were measured by enzyme-linked immunosorbent assay. Results: The aflibercept aqueous concentrations in the right eye at days 7, 14, 21, and 28 after injection were all significantly higher than those in the left eye (P > 0.05, n = 5). The peak aqueous concentrations of aflibercept in right eyes (49.5 μg/mL) and left eyes (50.9 μg/mL) were both observed at 1 day after injection. The elimination half-life of aflibercept in the aqueous humor of the right eye (4.70 days) was 1 day longer than that of the left eye (3.65 days). The average percentage of residual aflibercept in the vitreous humor of the right eye (3.35%) was also significantly higher than that of the left eye (0.63%). Conclusions: Brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops can significantly extend the ocular residence time of intravitreally injected aflibercept. [ABSTRACT FROM AUTHOR]

Objectives:To investigate the intraocular pressure (IOP)-lowering efficacy, safety, and treatment tolerability of brinzolamide/ brimonidine fixed combination (BBFC) in maximum medical therapy.Materials and Methods:The medical records of 92 patients with glaucoma or ocular hypertension who had previously been treated with a different antiglaucomatous regimen and were switched to a treatment regimen that included BBFC were retrospectively analyzed. Patients were divided into 4 groups including 22, 20, 27, and 23 patients based on previous glaucoma treatment. All patients received maximum medical treatment regimen by adding a combination of beta blocker-prostaglandin analogue therapy along with BBFC. IOP values at baseline and month 1, month 3 and month 6 after starting BBFC and ocular adverse effects at follow-up visits were evaluated.Results:The mean age of all patients was 62.7±16.6 years (range: 18-90). Fifty-two patients (56.5%) were women and 40 (43.5%) were men. Forty-eight (52.2%) patients had primary open-angle glaucoma, 35 (38.0%) had pseudoexfoliation glaucoma, and 9 (9.8%) had ocular hypertension. The IOP of the all eyes was 21.1±4.8 mmHg (range: 17-25) before and 17.6±3.7 mmHg, 17.3±3.4, and 17.0±3.5 mmHg at month 1, 3, and 6 after the introduction of BBFC, respectively (p

Brinzolamide (BRZ) is a highly selective carbonic anhydrase (CA) inhibitor which leads to decreases intraocular pressure (IOP) by slowing down the production of aqueous humour. It is indicated for the topical care of primary open-angle glaucoma (POAG) with ocular hypertension (OH), as 1% ocular suspension (Azopt) is applied twice or three times. A complex optic neuropathy known as POAG is characterized by the gradual loss of ganglion cells, including their axon. The main risk factor is elevated IOP, the only curable risk factor that can harm the optic head (ONH). To improve the absorption and bioavailability of BRZ in such eye-related complications, various drug delivery vehicles and nano-carriers such as Liposomes, In-situ Gelling systems, Nanofiber, TPGS-based nanoliposomes, Nanocapsules, Nanoemulsion, Niosomes and Nano lipid carrier are briefly suggested in the literature. Different strategies based on nano-carriers have shown to be successful for site-targeted delivery and demonstrate the basic structure with the altered pharmacodynamics property of BRZ. This review summarizes recent advancements in the management of glaucoma and the use of nano-carriers for molecular therapeutics of Glaucoma since it has distinct cellular targets, particularly the trabecular meshwork of the anterior portion of the eye.

A comparative study between two stability-indicating chromatographic methods for the assay of brinzolamide and timolol maleate in the co-existence of the probable carcinogenic oxidative degradation product of timolol maleate in their ophthalmic formulation was demonstrated. The first method established the thin-layer chromatography coupled with the densitometric determination of the analyzed spots, using silica gel TLC aluminum plates F254 and a developing system of chloroform: methanol: ammonia (6:1:0.1, in volumes) at room temperature to give good separation for the three investigated components, where retardation factors for the oxidative degradation product of timolol maleate, brinzolamide and timolol maleate were (Rf 0.21), (Rf 0.46), and (Rf 0.55), respectively. The linear ranges were 2–10 and 3–16 μg/band for brinzolamide and timolol maleate, respectively. In the second method, high performance liquid chromatography (HPLC), photo diode array detection was used on a Eurospher 5 µm C18 100 Å (4.6 × 250 mm) column, using triethylamine pH 3.5, adjusted by glacial acetic acid: acetonitrile (20:80, v/v) at a rate of 0.5 mL per minute. An acceptable separation was achieved, where the retention times for timolol maleate, the oxidative degradation product of timolol maleate and brinzolamide, were (Rt 3.6), (Rt 4.7), and (Rt 5.6), respectively. Linearity covered a range of 20–120 μg/mL for both drugs. It has been proved previously that timolol maleate is liable to oxidation, giving a high-probability carcinogenic product in female mice. The validation for the new proposed stability-indicating methods was optimized in line with the ICH guidelines with good outcomes. It is worth noting that the HPLC-DAD method showed superior separation, economic and time-saving results, while TLC method was more sensitive. [ABSTRACT FROM AUTHOR]

We evaluated switching from brinzolamide 1% or brimonidine 0.1% to a fixed-combination of brinzolamide 1% and brimonidine 0.1%, and then determined the efficacy, safety, and satisfaction associated with these changes in glaucoma patients. This prospective, nonrandomized study evaluated a total of 31 enrolled glaucoma patients who underwent treatment with at least brinzolamide 1% or brimonidine 0.1%. Patients were administered a brinzolamide/brimonidine fixed-combination ophthalmic suspension (BBFC) after being switched from their original brinzolamide 1% or brimonidine 0.1% therapy. All other intraocular pressure (IOP)-lowering medications currently being used were continued. IOP, superficial punctate keratopathy (SPK), and conjunctival hyperemia data obtained at baseline and then at 4 and 12 weeks were evaluated. To assess the changes in treatment satisfaction, this study utilized the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). There was a significant decrease in the mean baseline IOP from 15.7 ± 4.9 mmHg to 13.6 ± 4.4 (p = 0.001) and 13.5 ± 3.9 mmHg (p = 0.002) at 4 and 12 weeks, respectively. Evaluation of the incidence of conjunctival hyperemia or SPK score showed there were no significant changes noted at any time point. The TSQM-9 score demonstrated there was a significant increase for effectiveness after switching from brinzolamide 1% or brimonidine 0.1% to BBFC. After switching from brinzolamide 1% or brimonidine 0.1% to BBFC, there was a significant decrease in the IOP. Patients were aware of the effectiveness of switching from brinzolamide 1% or brimonidine 0.1% to BBFC. [ABSTRACT FROM AUTHOR]

Aim and Objective: To compare the efficacy and safety of brinzolamide1% and timolol0.5% fixed combination eye drops versus dorzolamide2% and timolol0.5% fixed combination eye drops in the treatment of primary open-angle glaucoma. Design: Prospective, randomized, comparative, interventional study. Setting: Tertiary eye care centre. Material and Method: The present study was a comparative study carried out on patients visiting OPD of Ophthalmology Department and diagnosed with primary open-angle glaucoma. Group 1 (n-30 BT) received brinzolamide1% and timolol0.5% fixed combination eye drops, and Group 2 (N-30 DT) patients received dorzolamide2% and timolol0.5% fixed combination eye drops. A complete ophthalmic examination was performed, including Goldmann applanation tonometry. IOP was measured twice daily (9 AM and 4 PM). The patients were evaluated at 2, 4, 8, and 12 weeks. IOP was measured at follow-up. Side effects and tolerability of both drugs were assessed, and patient preference for drugs was noted. Results: Mean reduction in morning IOP was significantly more in Group 1 than in Group 2 at 8 weeks and 12 weeks (p < 0.05). Mean reduction in evening IOP was significantly more in Group 1 than in Group 2 at all follow-ups (p < 0.05). Conclusion: Brinzolamide1% + timolol0.5% fixed drug combination is more preferred and effective in lowering IOP than dorzolamide2% + timolol0.5% fixed drug combination in patients of primary open-angle glaucoma.

Simple Summary: Carbonic anhydrase inhibitors such as dorzolamide, brinzolamide, and acetazolamide are prescription drugs prohibited in sports. Detecting these substances and their biomarkers of consumption in urine and hair is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment, and samples of the patients' relatives were analyzed to assess potential for accidental exposure. We found that cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. Additionally, we reported the first concentrations of brinzolamide in hair. Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients' relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 μL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2–501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9–125.3 ng/mL) for N-deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL–0.84 ng/mL) for N-acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4–79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7–437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1–0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06–0.08 ng/mg) for N-deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13–1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of switching to brimonidine/brinzolamide fixed combination (BBFC) eye drops on intraocular pressure (IOP) and safety. Study design: A retrospective observational study. Methods: We enrolled 238 patients with primary open-angle glaucoma or ocular hypertension who were switched to BBFC eye drops, from June 2020 to March 2021 from their previous medications without a washout period. Patients were divided into 3 groups based on previous medications: Group A, brimonidine and brinzolamide concomitantly; Group B, brinzolamide; and Group C, brimonidine. IOP at baseline, after 3 months, and after 6 months in each group were compared. Results: In Group A (n = 102), there was no difference in IOP at baseline (14.4 ± 3.0 mmHg), 3 months (14.1 ± 3.1 mmHg), and 6 months (13.9 ± 2.8 mmHg). In Group B (n = 104), IOP significantly decreased at 3 months and 6 months (baseline, 14.8 ± 3.0 mmHg; 3 months, 13.1±2.6 mmHg; 6 months 13.8±2.9 mmHg; P < 0.0001). In Group C (n = 32), IOP significantly decreased at 3 months and 6 months (baseline, 16.2 ± 3.5 mmHg; 3 months, 15.2 ± 3.5 mmHg; 6 months, 14.6 ± 3.2 mmHg; P < 0.01). Adverse reactions occurred in 6.9%, 18.3%, and 15.6% in Groups A, B, and C, respectively. The frequent adverse reactions in all patients were conjunctival hyperemia (3.4%), conjunctivitis (2.9%), blepharitis (2.9%), and itching (2.5%). Conclusion: BBFC had satisfactory IOP-lowering effects without serious adverse reactions in patients who switched medications. [ABSTRACT FROM AUTHOR]