Search

Brinzolamide is a topical carbonic anhydrase inhibitor which reduces the production of aqueous humor in the ciliary body, thereby reducing intra-ocular pressure. It is formulated as an ophthalmic suspension. The pharmacokinetics of ocular suspensions is not well understood. The objective of this study was to characterize the pharmacokinetics of brinzolamide in rabbit aqueous humor, iris-ciliary body, plasma, and whole blood. New Zealand White rabbits were dosed via intracameral, topical and intravenous administration. After intracameral administration (4.5 μg) of solubilized brinzolamide, aqueous humor concentrations were described with a two-compartment model, the estimated clearance was 4.12 μL/min, apparent volume of distribution at steady-state 673 μL, and terminal half-life 3.4 h. After topical administration of 1% brinzolamide suspension (500 μg), absolute bioavailability based on aqueous humor AUC 0-∞ was 0.10%. After intravenous administration of brinzolamide solution (0.75 mg/kg) elimination half-life in plasma and whole blood appeared to be over two weeks. The ratios of the measured concentrations of irisciliary body to whole blood, to plasma, and to aqueous humor concentrations enabled direct comparisons, and helped identify the significant contribution of the conjunctival-scleral pathways of absorption to the ciliary body. This study shows for the first-time the absolute bioavailability in aqueous humor and provides comprehensive pharmacokinetic parameters following administration of a topical suspension. [ABSTRACT FROM AUTHOR]

Objectives: The sense of smell plays an important role in daily life. Olfactory impairment can significantly affect an individual’s quality of life. Topical carbonic anhydrase inhibitors are commonly used to treat elevated intraocular pressure (IOP). One potential side effect of these drugs is a loss of the sense of smell. This study is an examination of changes in olfactory function in patients who used dorzolamide and brinzolamide to control IOP after a laser capsulotomy. Methods: A total of 60 patients with posterior capsule opacification were included in the study. Sniffin’ Sticks (Burghart Messtechnik GmbH, Wedel, Germany) were used to evaluate patient olfactory sensitivity before starting the topical treatment and after 1 week of treatment. Results: No statistically significant decrease in olfactory performance was observed in users of either brinzolamide or dorzolamide (p=0.705, p=0.405 respectively). Conclusion: No negative effect on the sense of smell was determined after 7 days of topical application of a carbonic anhydrase enzyme inhibitor to the eye in patients with no previous anosmia. [ABSTRACT FROM AUTHOR]

Co-delivery nanoparticles with characteristics of intracellular precision release drug have been generally accepted as an effective therapeutic strategy for eye diseases. In this study, we designed a new co-delivery system (miRNA/NP-BRZ) as a lasting therapeutic approach to prevent the neuro-destructive after the long-term treatment of glaucoma. Neuroprotective and intraocular pressure (IOP) response were assessed in in vivo and in vitro models of glaucoma. At the meaning time, we describe the preparation of miRNA/NP-BRZ, drug release characteristics, intraocular tracing, pharmacokinetic and pharmacodynamics study and toxicity test. We found that miRNA/NP-BRZ could remarkably decrease IOP and significantly prevent retinal ganglion cell (RGC) damages. The new formula of miRNA-124 encapsulated in PEG-PSA-BRZ nanoparticles exhibits high encapsulation efficiency (EE), drug-loading capacity (DC), and stable controlled-release efficacy (EC). Moreover, we also verified that the miRNA/NP-BRZ system is significantly neuroprotective and nontoxic as well as lowering IOP. This study shows our co-delivery drug system would have a wide potential on social and economic benefits for glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: We report the clinical courses of two patients with papillomacular retinoschisis in eyes with advanced glaucomatous optic neuropathy. Observations: In case 1, a 67-year-old woman was diagnosed with papillomacular retinoschisis and normal tension glaucoma in the left eye. Her medication was switched from topical latanoprost to brinzolamide, resulting in gradual improvement in the papillomacular retinoschisis thereafter. In case 2, a 76-year-old man was diagnosed with papillomacular retinoschisis, foveal detachment, and normal tension glaucoma in the left eye. His medication was switched from topical tafluprost/timolol to brinzolamide, resulting in gradual improvement in the papillomacular retinoschisis and foveal detachment thereafter. Conclusionsand Importance: Papillomacular retinoschisis may occur in eyes with advanced glaucomatous optic neuropathy. Topical brinzolamide therapy may lead to improvement of papillomacular retinoschisis.

AIM: To investigate if significant improvement of optic disc blood flow (ODBF) occurs after instillation of brinzolamide onto rabbit eyes. METHODS: Testing of bilateral intraocular pressure (IOP) and left ODBF in 10 male rabbits took place every 3h over a 24h period. Brinzolamide (1% ophthalmic solution, two drops at 9:00 and 21:00) was administered to the left eye. ODBF, assessed using laser speckle flowgraphy, was determined as the mean blur rate (MBR). Furthermore, the effect of brinzolamide on isolated rabbit ciliary arteries using isometric tension recording system was performed. RESULTS: After brinzolamide instillation, IOP was significantly decreased in the left eye. MBR-vessel was greater at 18:00 and 21:00 (P

A neurodegenerative disorder, glaucoma is a leading cause of blindness in the world. The conventional treatment strategies do not allow the significant penetration of the drug in the cornea. Therefore, we prepare a brinzolamide (Brz) loaded core-shell nanoparticles (NPs) to enhance the coronial penetration of the drug and thus treating the glaucoma. The shell of the NPs was composed of phosphatidylserine (PS; 1,2-diacyl-sn-glycero-3-phospho-L-serine), whereas the core of the NPs contains the Brz encapsulated in brinzolamide–phosphatidylserine–polymer poly-(DL-lactic acid-co-glycolic acid)–phosphatidylserine (Brz-PS-PLGA). The synthesis of Brz-PS-PLGA was achieved by using a coaxial electrospray process (CEP), which allows the preparation of the particles in a single step. The size of Brz-PS-PLGA with PS shell and brinzolamide–poly (lactic-co-glycolic) acid (Brz-PLGA) without shell was 571 ± 27.02 nm and 456 ± 19.17 nm, respectively. The charges on the surface of Brz-PS-PLGA and Brz-PLGA were (-) 27.45 ± 2.98 mV and (-) 19.47 ± 2.83 mV. The transmission electron microscopy images clearly reveal the PS shell as a light black layer over the dark black PLGA core. The CEP allows the high encapsulation of Brz in Brz-PS-PLGA where percentage of entrapment efficiency for Brz-PS-PLGA was 88.13 ± 6.43%. The release study conducted in a simulated tear fluid revealed the sustained release patterns of Brz from Brz-PS-PLGA and these were nontoxic to the cells as revealed by the cytotoxicity studies. Further, the Brz-PS-PLGA enhanced the coronial penetration of Brz and was capable of significantly reducing the intraocular pressure (IOP) after administration to the rabbit eye in comparison to the Brz-PLGA and free Brz. The results clearly suggest that the PS coating significantly enhances the capability of the particles in reducing IOP. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to compare the daily costs and cost effectiveness of fixed combination glaucoma drugs in China. Methods. This study included the following fixed combination drugs: brinzolamide 1% and timolol 0.5% (Azarga; Alcon, Inc., Fort Worth, TX, USA), travoprost 0.004% and timolol 0.5% (DuoTrav; Alcon, Inc.), bimatoprost 0.03% and timolol 0.5% (Ganfort; Allergan, Inc., Dublin, Ireland), and latanoprost 0.005% and timolol 0.5% (Xalacom; Pfizer, Inc., New York, NY, USA). Five bottles of each drug were measured. The mean actual volume, mean actual number of drops, volume per drop, daily cost, yearly cost, and per mmHg reduction cost for each drug were calculated. Results. The volumes per drop ranged from 32.61 ± 2.90 μl (DuoTrav) to 24.38 ± 0.23 μl (Ganfort). The number of usage days per bottle varied from 36 days (DuoTrav) to 61 days (Ganfort). Azarga had the lowest daily cost ($0.23) and yearly cost ($84.72), while DuoTrav had the highest daily cost ($0.79) and yearly cost ($287.02). Azarga costed $2.17–$3.30 per mmHg intraocular pressure reduction, which was lower than the other three drugs. For the prostaglandin and ß-adrenergic blocker FCs, Ganfort had the lowest daily cost ($0.35) and per mmHg reduction cost (from $3.40 to $4.04). Conclusions. The daily costs of these drugs were significantly different, with Azarga having the lowest daily cost and best cost effectiveness. For the prostaglandin and β-adrenergic blocker fixed combinations, Ganfort was the most economical choice with its lower daily cost and per mmHg reduction cost. The results of this study could provide drug selection guidance from an economic perspective, but various factors should be considered when making a decision. [ABSTRACT FROM AUTHOR]

Commercially available eye-drops scarcely penetrate the eye because of the cornea, which is located at the surface of the eye and function of barrier to keep out foreign matter. To enhance the penetration ratio of eye-drop, we have proposed nanometer-sized eye-drops called "nano eye-drops." A series of prodrug compounds derived from brinzolamide, a glaucoma therapeutic agent, connected with a trimethyl lock (TML) group were synthesized and the nano eye-drops of the resulting prodrugs were successfully fabricated by the reprecipitation method. We found that the drug release of nano eye-drops critically depended on the chemical structure of the prodrugs comprising the nano eye-drops. As a result, the timing of the ocular hypotensive effect was controlled by altering the chemical structure of brinzolamide prodrug. These results provide insight into drug design for effective controlled release. [ABSTRACT FROM AUTHOR]

Present study involves the development of simple, accurate, rapid, sensitive and stability indicating RP_HPLC method for the determination of Brimonidine Tartrate in bulk and Brimonidine Tartrate and Brinzolamide ophthalmic suspension. In a gradient program with a flow rate of 1.2 mL/min, 1 mL orthophosphoric acid and 1 mL triflouroacetic acid in 1000 mL (Mobile Phase 1) and a mixture of acetonitrile and methanol in the ratio 40:60 v/v (Mobile Phase 2) were used. Brimonidine tartrate has a retention time of 16.907. At a wavelength of 248nm, UV detection was performed. Chromatographic separation was achieved using a 5m HPLC column made of inert sustain C18 (250*4.6). As per ICH guidelines, the method was validated using current ICH guidelines for method validation parameters such as specificity, linearity, system suitability, system precision, and method precision. Within test ranges, the Brimonidine Tartrate showed regression (R2>0.9999), and percentage recovery was found to be 99.7% in the marketed formulation. The method was found to be highly specific, with no interference from Brimonidine Tartrate impurities. [ABSTRACT FROM AUTHOR]

Glaucoma is an ocular disease i.e.more common in older adults with elevated intraocular pressure and a serious threat to vision if it is not controlled. Due to the limitations regarding the conventional form of brinzolamide (Azopt®), two optimum formulations of in situ gel nanoemulsion were developed. To ensure the safety and efficacy of developed formulations for ocular drug delivery, the current study was designed. MTT assay was carried out on the human retinal pigmentation epithelial cells. To investigate the irritation potential of the chosen formulations, hen's egg test-chorioallantoic membrane as a borderline test between in vivo and in vitro methods has been done. The modified Draize method was utilized to evaluate eye tolerance against the selected formulations. Intraocular pressure was measured by applying the prepared formulations to the eyes of normotensive albino rabbits in order to assess the therapeutic efficacy. Based on MTT test, cell viability for NE-2 at 0.1% and NE-1 at 0.1 and 0.5% concentrations was acceptable. The results of the hen's egg test-chorioallantoic membrane test indicated no sign of vessel injury on the chorioallantoic membrane surface for both formulations. Also, during 24 h, both formulations were well-tolerated by rabbit eyes. The pharmacodynamics effects of formulations had no difference or were even higher than that of suspension in case of adding lower concentration (0.5%) of brinzolamide to the formulations.With regard to the results of the mentioned methods, our advanced formulations were effective, safe, and well-tolerated, thus can be introduced as an appropriate vehicle for ocular delivery of brinzolamide. [ABSTRACT FROM AUTHOR]

Brinzolamide (BNZ) is a carbonic anhydrase inhibitor commonly used for the treatment of glaucoma. The aim of this study was to prepare BNZ loaded chitosan-pectin mucoadhesive nanocapsules (CPNCs) by polyelectrolyte complex coacervation method for ocular delivery and evaluated for its anti glaucoma efficacy. The prepared CPNCs were characterized for their particle size, polydispersity index, zeta-potential, surface morphology, entrapment efficiency, drug loading efficiency, mucoadhesive strength in-vitro and ex-vivo release. The pharmacodynamic studies were conducted for CPNCs on glaucoma induced rabbit eye model and compared with marketed product. All the formulated CPNCs exhibited the size range from 217.01 ± 0.21 to 240.05 ± 0.08 nm and appropriate physico-chemical parameters, and depicted a couple of erosion- diffusion release of BNZ over a time of 8 h. Ex-vivo corneal permeation study concluded that BNZ loaded CPNCs crosses the cornea potentially higher rate as compared to the marketed product. In pharmacodynamic study, greater intraocular pressure lowering effect was achieved by CPNCs as compared to marketed drug product. The result concluded that CPNCs are a feasible choice to conventional eye drops because of its ability to improve the bioavailability via its longer precorneal retention time and its ability to sustained release of the drug. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is most common irreversible cause of blindness in India. First line management of open-angle glaucoma is either beta blockers or prostaglandin analogs monotherapy. Monotherapy rarely achieves target intraocular pressure within 2 years and patients are shifted to combination medications, usually fixed-dose combination. Objective: To compare travoprost monotherapy and timolol/brinzolamide fixed-dose combination for their intraocular pressure lowering efficacy, their effects on hemodynamic parameters and cup disc ratio reversibility in newly diagnosed drug-naïve open-angle glaucoma patients. Material and methods: In a 12-week, prospective, randomised, single-blind study, patients were randomised to receive twice daily 0.5% timolol and 0.2% brinzolamide fixed-dose combination (n = 52) or once daily travoprost 0.004% (n = 52). Intraocular pressure, blood pressure, pulse rate and cup disc ratio were compared across treatment groups over 3 months. Results: Significant reduction (p < 0.001) in intraocular pressure by 27.99% and 30.49% at 12th-week visit as compared with baseline was observed in monotherapy and fixed-dose combination group, respectively. Significant changes in pulse rate (9 beats/min) and systolic blood pressure (2.35 mmHg) was observed in fixed-dose combination group. No cup disc ratio reversibility was observed at the end of study. Conjunctival hyperaemia (n = 14) and transient blurring of vision (n = 16) were most commonly reported adverse drug reaction in monotherapy and fixed-dose combination, respectively. Conclusion: The 0.5% timolol and 0.2% brinzolamide fixed-dose combination produced greater reduction in intraocular pressure than those produced by 0.004% travoprost alone in drug-naïve open-angle glaucoma patients. [ABSTRACT FROM AUTHOR]

The present research work summarises the development of an in situ gelling ophthalmic nanoemulsion of brinzolamide providing sustained release and prolonged therapeutic effect for the treatment of glaucoma. Nanoemulsions were prepared using castor oil, polyoxyl 35 castor oil and polysorbate 80 and with gellan gum as the in situ gelling agent. Formulations were screened based on globule size, Zeta potential, in vitro drug release and stability towards phase separation and sol to gel conversion upon storage. Selected formulations exhibiting a low mean globule diameter (< 160 nm), narrow size distribution (polydispersity index < 0.3), quick in vitro gelling time (< 15 s) and stability for at least 6 months at 25 °C/40% RH and 40 °C/25% RH were evaluated for intraocular pressure (IOP)-lowering efficacy studies using glaucomatous rabbits. Tested nanoemulsion formulations were well tolerated and significantly decreased IOP relative to saline and placebo controls (p < 0.005). Furthermore, an appreciable increase in the area under change in IOP from baseline (ΔIOP) vs. time curve and a longer mean residence time (MRT) was also observed for the test formulations compared with commercially available suspension of brinzolamide (Azopt, Alcon Laboratories, USA). Thus, nanoemulsion formulations containing in situ gelling polymer may serve as improved drug delivery system providing superior therapeutic efficacy and better patient compliance for the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the present work, a cost-effective, stable and sustained release ophthalmic solution formulation of brinzolamide (BRZ) was developed for the treatment of glaucoma. The prototype formulation undergoes 'in situ gelling' when administered in the eye, thereby providing longer residence (16–24 h). As a result, the same therapeutic endpoint is achieved with once daily dosing vis-à-vis the commercially available product Azopt® (brinzolamide 1.0% w/v, Alcon Laboratories, USA) that requires 3–4 times instillations per day. The prototype formulations were prepared using dimethyl sulfoxide, polyoxyl 35 castor oil and polysorbate 80. Gellan gum was used as the in situ gelling agent. Formulation variables like (i) concentration of the drug, dimethyl sulfoxide and in situ gelling agent and (ii) type and concentration of solubiliser showed a significant effect on the solubility of brinzolamide, in vitro gelling time, in vitro drug release and in situ gel stability. Prototype formulations were evaluated in New Zealand white rabbits for ocular toxicity and efficacy study. The tested formulations were well tolerated and reduced intraocular pressure (IOP) from 25–28 to 12–14 mmHg compared to saline and placebo control samples. Additionally, a significant increase in the area under change in IOP from baseline (ΔIOP) vs. time curve and a longer mean residence time (MRT) were also observed for the test formulations (7.4 to 17.7 h) compared to the commercially available suspension of Azopt® (4.9 h) (p < 0.0001). Thus, 'in situ gelling' formulation strategy described in this work can work as a viable option for ocular delivery of brinzolamide for the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

The aim of this study was to report the outcome of topical brinzolamide 1% treatment on macular cystoid lesions resembling retinoschisis in 4 patients diagnosed with posterior microphthalmia. The medical records of 4 patients with a clinical diagnosis of posterior microphthalmia who had started topical brinzolamide 1% treatment were reviewed. Visual acuity, central foveal thickness, and cystoid lesion area percentage were used to evaluate treatment response. In the follow-up, there was a decrease in central foveal thicknesses and cystoid lesion area percentages in both eyes of 3 of the patients. However, 1 patient showed increases in both parameters. Visual acuity remained stable in 5 eyes and increased in 3 eyes. Topical brinzolamide treatment may have some positive effects on macular cystoid lesions in selected cases. [ABSTRACT FROM AUTHOR]

Brinzolamide is inhibitor of carbonic anhydride and is highly specific and non-competitive. The aim of the present study is to develop a simple, precise, accurate, sensitive RP-HPLC method for the determination of bulk drug. The objective of the method validation is to demonstrate whether the method was suited for the intended purpose. The method was validated as per the ICH guidelines. The method was validated for linearity, precision (repeatability, intermediate precision), accuracy, specificity, robustness, ruggedness, limit of detection and limit of quantification. Cosmosil (4.6X250mm, 5 µ) column was used for separation. The selected wavelength for Brinzolamide was 254 nm. The mobile phase consists of Acetonitrile: Potassium dihydrogen phosphate buffer (40:60). Flow rate was delivered at 1.0 mL/min. Appropriate dilutions of standard stock solutions were prepared to get desired concentrations in the range of 100-500 mcg/ml. The equation od standard curve was y = 441.8x + 1132 and R2 = 0.998. The RT obtained was 6.6167 minutes. [ABSTRACT FROM AUTHOR]

[Display omitted] The intricate structure of the eye poses difficulties in drug targeting, which can be surmounted with the help of nanoformulation strategies. With this view, brinzolamide nanosponges (BNS) were prepared using the emulsion solvent evaporation technique and optimized via Box-Behnken statistical design. The optimized BNS were further incorporated into a poloxamer 407 in situ gel (BNS-ISG) and evaluated. The optimized BNS showed spherical morphology, entrapment efficiency of 83.12 ± 1.2 % with particle size of 114 ± 2.32 nm and PDI of 0.11 ± 0.01. The optimized BNS-ISG exhibited a pseudoplastic behavior and depicted a gelling temperature and gelation time of 35 ± 0.5 °C and 10 ± 2 s respectively. In- vitro release and ex- vivo permeation studies of BNS-ISG demonstrated a sustained release pattern as compared to Brinzox®. Additionally, the HET-CAM and in vitro cytotoxicity studies (using SIRC cell line) ensured that the formulation was non-irritant and nontoxic for ophthalmic delivery. The in vivo pharmacodynamic study using rabbit model depicted that BNS-ISG treatment significantly lowers the intra ocular pressure for prolonged period of time when compared with Brinzox®. In conclusion, the BNS-ISG is an efficient and scalable drug delivery system with significant potential as the targeted therapy of posterior segment eye diseases. [ABSTRACT FROM AUTHOR]