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Purpose: Chronic ailments usually decrease the quality of life due to the requirement for repetitive administration of drugs. Glaucoma is a chronic eye disease occurred because of increased intraocular pressure (IOP). Controlled-release inserts can overcome this challenge by a gradual release of the antiglaucoma drugs. This study aimed to fabricate ocular inserts of brimonidine tartrate (BMD) for the management of glaucoma. Methods: Different polymers including poly (D, L-lactide), polycaprolactone, cellulose acetate, and Eudragit RL100® were used to develop the BMD-loaded nanofibrous inserts by electrospinning technique. The inserts were characterized. The morphology and drug-polymer compatibility were examined by scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy and in vitro drug release in PBS. The IOP-lowering efficacy and irritancy of optimized formulation were assessed in the caprines. Results: SEM images demonstrated nanofibers with uniform morphology and a mean diameter<300 nm were fabricated. The nanofibers were high-strength and flexible enough to be placed in the conjunctival sac. FTIR showed drug-polymer compatibility. In vitro release study indicated a sustained-release profile of the drug during 6 days for inserts. In vivo evaluation indicated that the optimized formulation is capable of maintaining the IOP in a non-glaucomatous range for an extended duration of 6 days. In addition, the formulation was non-irritant to the caprine eye. Conclusion: Due to the prolonged IOP-lowering efficiency, BMD-loaded nanofibrous inserts can be considered suitable for the controlled release of drugs and thus enhance patient compliance by reducing the frequency of administration.
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Brimonidine is a third-generation alpha-2 adrenergic agonist and is classified as an ocular hypotensive agent. It is used for chronic glaucoma treatment by lowering intraocular pressure, crucial for preventing blindness. Brimonidine works by reducing aqueous humor production and increasing uveoscleral outflow. The improper use of brimonidine in children can result in severe adverse effects. If brimonidine eye drops are ingested orally, it can cause significant depression of the cardiorespiratory and central nervous systems. This is a case report of a 27-day-old neonate, who presented with central nervous system and respiratory depression after accidental ingestion of one drop of brimonidine tartrate ophthalmic solution. On arrival, he was having shallow breathing, a low Glasgow Coma Scale score, pinpoint pupils, and absent deep tendon reflexes. Gastric lavage was performed and supportive treatment was started. The patient showed gradual improvement and completely recovered within 48 hours.
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RESUMO Objetivo: Avaliar o efeito do colírio de brimonidina 0,2% na redução da hiperemia e do sangramento ocular durante as cirurgias de estrabismo, em comparação com o colírio de nafazolina 0,025% + feniramina 0,3%. Métodos: Foram avaliados 14 pacientes com estrabismo e indicação de correção cirúrgica bilateral. Foi instilado antes do procedimento, de forma aleatória, um colírio em cada olho dos pacientes avaliados. A análise subjetiva da hiperemia conjuntival e do sangramento perioperatório foi realizada de forma duplo-cega, por dois cirurgiões. A avaliação objetiva do nível de hiperemia conjuntival foi realizada por análise das imagens obtidas por meio do software ImageJ®. Resultados: A análise de modelos multivariados de efeito misto indicou diferenças estatisticamente significantes entre os grupos em relação à hiperemia (avaliador 2) e ao sangramento intraoperatório (avaliadores 1 e 2), com maiores escores nos casos tratados com colírio de nafazolina + feniramina. Entretanto, não houve diferença estatística na análise objetiva realizada por meio da saturação de cores obtidas pelo programa ImageJ®. Conclusão: O colírio de brimonidina pode ser superior ao colírio de nafazolina + feniramina na redução do sangramento, levando-se em conta apenas a análise subjetiva.
ABSTRACT Objective: To evaluate the effect of 0.2% brimonidine eye drops in reducing hyperemia and ocular bleeding during strabismus surgeries, in comparison with 0.025% naphazoline + 0.3% pheniramine eye drops. Methods: Fourteen patients with strabismus and indication for bilateral surgical correction were evaluated. Before the procedure, the eye drops were instilled randomly in each eye of the evaluated patients. The subjective analysis of conjunctival hyperemia and perioperative bleeding was performed in a double-blind manner, by 02 surgeons. The objective assessment of the level of conjunctival hyperemia was performed by analyzing the images obtained using the ImageJ® software. Results: The analysis of multivariate mixed effect models indicated statistically significant differences between the groups in relation to hyperemia (rater 2) and intraoperative bleeding (raters 1 and 2) with higher scores in cases treated with naphazoline + pheniramine eye drops. However, there were no statistically significant differences in the objective analysis of color saturation obtained by the ImageJ® program. Conclusion: Brimonidine eye drops may be superior to naphazoline + pheniramine eye drops in reducing bleeding, taking into account the subjective analysis only.
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Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Feniramina/administración & dosificación , Hemorragia del Ojo/prevención & control , Estrabismo/cirugía , Tartrato de Brimonidina/administración & dosificación , Hiperemia/prevención & control , Complicaciones Intraoperatorias/prevención & control , Nafazolina/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Premedicación , Procedimientos Quirúrgicos Oftalmológicos/métodos , Vasoconstricción/efectos de los fármacos , Fotograbar , Método Doble Ciego , Administración Tópica , Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Hemostasis Quirúrgica/métodosRESUMEN
PURPOSE: A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). STUDY DESIGN: This was a prospective, open-label, multicenter study. PATIENTS AND METHODS: We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. RESULTS: We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg (P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg (P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by - 2.0 ± 1.8 mmHg (P < 0.0001) and -1.9 ± 1.4 mmHg (P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. CONCLUSIONS: BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.
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Glaucoma de Ángulo Abierto , Hipertensión Ocular , Humanos , Tartrato de Brimonidina , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Estudios Prospectivos , Pueblos del Este de Asia , Antihipertensivos/uso terapéutico , Presión Intraocular , Hipertensión Ocular/tratamiento farmacológico , Prostaglandinas Sintéticas/uso terapéutico , Timolol , Combinación de MedicamentosRESUMEN
Aims: 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. Methods: 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. Results: 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). Conclusion: 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.
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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.
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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.
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Enfermedades de la Córnea , Humanos , Tartrato de Brimonidina/uso terapéutico , Soluciones Oftálmicas , Microscopía Confocal , LípidosRESUMEN
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.
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Hiperemia , Agonistas alfa-Adrenérgicos , Tartrato de Brimonidina/efectos adversos , Eritema/tratamiento farmacológico , Humanos , Hiperemia/inducido químicamente , Hiperemia/tratamiento farmacológico , Descongestionantes Nasales , Soluciones Oftálmicas/efectos adversos , Calidad de Vida , Quinoxalinas/efectos adversos , Receptores AdrenérgicosRESUMEN
Background: The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule. Research Design and Methods: GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated. Results: The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution. Conclusions: Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.
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Glaucoma , Liposomas , Animales , Tartrato de Brimonidina , Presión Intraocular , Liposomas/química , Plastificantes , ConejosRESUMEN
PURPOSE: To evaluate the efficacy of preoperative topical brimonidine use to maintain visibility during trabeculectomy and control intraoperative bleeding and postoperative subconjunctival hemorrhage. METHODS: The first group comprised 35 eyes of 34 patients administered brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops 6 and 3â min before surgery, and 33 eyes of 31 patients who received no medication for vasoconstriction formed the second group. Preoperative and postoperative photographs and operation video images were taken and vision analysis software used. Black-and-white images were obtained to identify the blood vessel and surface hemorrhage areas. The surface area of the hemorrhage was calculated by counting the black pixels with Image J software. RESULTS: There was no significant difference between two groups in terms of baseline (preoperative) eye redness (p > 0.05). In the first group, the eye redness values were 344.7 ± 19.5 pixels preoperatively and 244.1 ± 23.3 pixels at the beginning of the surgery, respectively (p < 0.001). However, no significant change was observed in the second group in eye redness (348.2 ± 17.5 pixels preoperatively and 360.7 ± 26.8 pixels at the beginning of the surgery, p > 0.05). Cautery was used for an average of 11.91 ± 1.96 s in the first group and 25.57 ± 4.66 s in the second to control intraoperative bleeding (P < 0.001). CONCLUSION: Preoperative topical brimonidine use in trabeculectomy surgery significantly decreased intraoperative bleeding and postoperative subconjunctival hemorrhage and facilitated bleeding control.
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Enfermedades de la Conjuntiva , Hemorragia del Ojo , Trabeculectomía , Tartrato de Brimonidina , Enfermedades de la Conjuntiva/tratamiento farmacológico , Enfermedades de la Conjuntiva/etiología , Enfermedades de la Conjuntiva/prevención & control , Hemorragia del Ojo/tratamiento farmacológico , Hemorragia del Ojo/etiología , Hemorragia del Ojo/prevención & control , Humanos , Presión Intraocular , Soluciones Oftálmicas , Quinoxalinas/uso terapéuticoRESUMEN
Persistent post acne erythema (PAE) is common cosmetically unacceptable and challenging sequelae of acne lesions. Tranexamic acid (TXA) is an antifibrinolytic agent that shows a positive effect on wound healing in several studies, and it showed benefits in treating skin diseases like melasma, rosacea erythema and ultraviolet induced pigmentations. Oxymetazoline (OXZ) is a synthetic, highly selective agonist for alpha 1A-adrenoceptor. It is a potent vasoconstrictor. OXZ hydrochloride 1% cream was approved by the FDA in January 2017 as a topical treatment for persistent facial erythema in rosacea patients. Brimonidine tartrate (BMT) is highly selective α2 adrenergic receptor agonist, results in direct, potent vasoconstriction of small arterioles and veins. In 2013, brimonidine 0.33% gel was the first topical therapy to be FDA approved for the treatment of persistent facial erythema from rosacea. To evaluate the efficacy and safety of topical triple combination (TXA 5% + OXZ 1.5% + BMT 0.33%) in the treatment of PAE planned as split face comparative study. This study was conducted on 40 patients diagnosed with persistent PAE for at least 3 months, the right side of the face was treated with topical triple combination in liposomal base and was compared to the left side to which topical lipocream (placebo) was applied as a control. Our treatment plan lasted for 3 months. According to the investigator's global assessment of photographs and computerized analysis of erythema using image analysis software, topical triple combination applied on the right side of face was significantly effective in diminishing PAE when compared to topical placebo left side. Topical triple combination is a safe and cost-effective treatment for PAE.
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Acné Vulgar , Eritema , Acné Vulgar/complicaciones , Acné Vulgar/tratamiento farmacológico , Administración Tópica , Tartrato de Brimonidina/administración & dosificación , Quimioterapia Combinada/efectos adversos , Eritema/tratamiento farmacológico , Eritema/etiología , Humanos , Oximetazolina/administración & dosificación , Rosácea/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Quantitation of ocular drug metabolism is important, but only sparse data is currently available. Herein, the pharmacokinetics of four drugs, substrates of metabolizing enzymes, was investigated in albino rabbit eyes after intracameral and intravitreal administrations. Acetaminophen, brimonidine, cefuroxime axetil, and sunitinib and their corresponding metabolites were quantitated in the cornea, iris-ciliary body, aqueous humor, lens, vitreous humor, and neural retina with LC-MS/MS analytics. Non-compartmental analysis was employed to estimate the pharmacokinetic parameters of the parent drugs and metabolites. The area under the curve (AUC) values of metabolites were 12-70 times lower than the AUC values of the parent drugs in the tissues with the highest enzymatic activity. The ester prodrug cefuroxime axetil was an exception because it was efficiently and quantitatively converted to cefuroxime in the ocular tissues. In contrast to the liver, sulfotransferases, aldehyde oxidase, and cytochrome P450 3A activities were low in the eye and they had negligible impact on ocular drug clearance. With the exception of esterase substrates, metabolism seems to be a minor player in ocular pharmacokinetics. However, metabolites might contribute to ocular toxicity, and drug metabolism in various eye tissues should be investigated and understood thoroughly.
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Preparaciones Farmacéuticas , Animales , Cromatografía Liquida , Conejos , Retina , Espectrometría de Masas en Tándem , Cuerpo VítreoRESUMEN
CLINICAL RELEVANCE: Posterior capsule opacification is a common late complication of cataract surgery. Posterior capsule opening with Nd:YAG laser, which is the standard treatment, may cause transient elevation of intraocular pressure (IOP). BACKGROUND: To evaluate the efficacy of betaxolol 0.|5% compared to brimonidine 0.2%, in prevention of intraocular pressure increase after Nd:YAG Laser posterior capsulotomy. METHODS: In a double masked randomised clinical trial, 38 eyes from 38 pseudophakic patients over 21 years of age who had significant posterior capsule opacification after phacoemulsification were randomly assigned to receive either betaxolol 0.|5% (18 eyes) or brimonidine 0.|2% (20 eyes) one hour before Nd:YAG Laser posterior capsulotomy.| Exclusion criteria were: glaucoma or history of glaucoma surgery, active uveitis, active ocular infection, pregnancy, unstable cardiovascular condition and severe asthma and lung diseases. Intraocular pressure was measured by Goldmann applanation tonometry, 1 hour before applying the laser and 4 hours after the laser application. RESULTS: There was no statistically significant difference between the two groups regarding the baseline mean IOP and the 4-hour post-laser mean IOP. There was a statistically significant decrease in the 4-hour post-laser mean IOP as compared to the baseline mean IOP in each group. The mean IOP change in the betaxolol group, was -2.39 ± 1.79 mm Hg and in the brimonidine group was -4.25 ± 2.20 mm Hg. The difference was statistically significant (P = 0.007). None of the patients experienced clinically significant IOP increase (≥5 mm Hg) in either group. CONCLUSION: Use of a single topical dose of betaxolol 0.5% and brimonidine 0.2%, 1 hour before laser treatment, can prevent significant acute IOP increase after Nd:YAG laser posterior capsulotomy, and betaxolol may provide a new alternative for prophylactic use.
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Opacificación Capsular , Glaucoma , Cápsula del Cristalino , Hipertensión Ocular , Humanos , Presión Intraocular , Tartrato de Brimonidina/uso terapéutico , Betaxolol/uso terapéutico , Opacificación Capsular/cirugía , Hipertensión Ocular/etiología , Hipertensión Ocular/prevención & control , Capsulotomía Posterior/efectos adversos , Glaucoma/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Anestesia General/métodos , Tartrato de Brimonidina/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/efectos adversos , Animales , Tartrato de Brimonidina/efectos adversos , Relación Dosis-Respuesta a Droga , Ratones , ConejosRESUMEN
Purpose: The aim of this study was to formulate brimonidine tartrate loaded phase transition microemulsions (PMEs), which undergo phase transition from water in oil (W/O) microemulsions to liquid crystalline (LC) and then oil in water (O/W) microemulsions after instilled into the eye and prolong the precorneal residence time and ocular bioavailability for the effective treatment of glaucoma.Methods: The pseudo-ternary phase diagram was developed and various PMEs were prepared using Tween 80 and Span 80 with isopropyl myristate and water. Globule size and shape, physicochemical parameters, in vitro and ex vivo drug release of PMEs were studied. The in vivo anti-glaucoma efficacy of optimized PMEs was studied in an experimental rabbit eyes model and compared with marketed formulation (MF).Results: Globule size of PMEs was found less than 200 nm, which was confirmed by both dynamic light scattering technique and Transmission Electron Microscopy. Physicochemical properties such as pH, refractive index, percentage transparency, viscosity and conductivity were also found in the acceptable ranges. In vitro release studies of PMEs exhibited sustained release property. Ex vivo permeation study also supported the enhanced drug flux through cornea from PMEs as compared with MF. In pharmacodynamic study, a greater reduction in intraocular pressure was seen in PMEs as compared to MF.Conclusion: PMEs as ocular drug delivery system offer a promising approach to enhance the corneal contact, higher permeation and prolonged precorneal retention time in the eye leading to sustained drug release, enhanced bioavailability and patient compliance.
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Tartrato de Brimonidina/farmacocinética , Córnea/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Glaucoma/tratamiento farmacológico , Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Animales , Córnea/metabolismo , Modelos Animales de Enfermedad , Liberación de Fármacos , Emulsiones/farmacocinética , Glaucoma/metabolismo , Glaucoma/fisiopatología , Cabras , Presión Intraocular/efectos de los fármacos , Tamaño de la Partícula , ConejosAsunto(s)
Antihipertensivos/efectos adversos , Tartrato de Brimonidina/efectos adversos , Dermatitis Alérgica por Contacto/diagnóstico , Soluciones Oftálmicas/efectos adversos , Anciano , Antihipertensivos/administración & dosificación , Tartrato de Brimonidina/administración & dosificación , Humanos , Masculino , Soluciones Oftálmicas/químicaRESUMEN
Purposes: The present study aimed to develop brimonidine tartrate loaded poly(lactic-co-glycolic acid) acid vitamin E-tocopheryl polyethylene glycol 1000 succinate (BRT-PLGA-TPGS) nanoparticles in thermosensitivein situ gel to improve mucoadhensive properties and drug holding capacity for the better management of glaucoma.Methods: Nanoparticles was optimized by means of Box-Behnken Design (BBD). The formulations were prepared using various concentration of PLGA (0.1-0.4% w/v) and TPGS (0.3-0.5% w/v). The analytical data of fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) depicted the drug excipients compatibility and confirmed the nanoparticles. Nanoparticles incorporated gel was evaluated for transcorneal permeability, gelation time, gelling temperature, and rheological studies. In addition, in vitro, transcorneal permeation drug release studies and intraocular pressure (IOP) for optimized gel was also performed. Biocompatibility of formulations was investigated in rabbit model.Results: The drug loaded nanoparticles exhibited 115.72 ± 4.18 nm, 0.190 ± 0.02, -11.80 ± 2.24 mV and 74.85 ± 6.54% of mean size, polydispersity index (PDI), zeta potential and entrapment efficiency (% EE), respectively. As compared to marketed eye drop, the sustained and continuous release BRT release from Poloxamer-based in situ gel was 85.31 ± 3.51% till 24 h. The transcorneal steady-state flux (136.32 µg cm-2 h-1) of optimized in situ gel was approximately 3.5 times higher than marketed formulation (38.60 µg cm-2 h-1) flux at 4 h. The optimized formulation produces 3 fold greater influences on percentage reduction of IOP (34.46 ± 4.21%) than the marketed formulation (12.24 ± 2.90%) till 8 h.Conclusion: The incorporation of optimized BRT-PLGA-TPGS nanoparticles into a thermosensitivein situ gel matrix to improve precorneal residence time without causing eye irritation and also serve the sustained release of BRT through cornea for effective management of glaucoma.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Tartrato de Brimonidina/farmacología , Sistemas de Liberación de Medicamentos , Glaucoma/tratamiento farmacológico , Sistema de Administración de Fármacos con Nanopartículas/química , Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Agonistas de Receptores Adrenérgicos alfa 2/toxicidad , Animales , Tartrato de Brimonidina/farmacocinética , Tartrato de Brimonidina/toxicidad , Rastreo Diferencial de Calorimetría , Pollos , Membrana Corioalantoides/efectos de los fármacos , Córnea/metabolismo , Cabras , Presión Intraocular/efectos de los fármacos , Microscopía Electrónica de Transmisión , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Conejos , Espectroscopía Infrarroja por Transformada de Fourier , Vitamina E/químicaRESUMEN
The main objective of the study is to develop a suitable and rapid UPLC/PDA method by coupling online to Quadrupole Dalton analyzer (QDa), a mass detector for the identification and impurity profiling of Brimonidine Tartrate (BRIM)/Timolol maleate (TIMO) in the ophthalmic formulation. Chromatographic separation was achieved on ethylene bridged hybrid octadecylsilane column having 1.7µm particle size in gradient mode using high pure heptafluorobutyric acid as a buffer (A) and water, methanol, and acetonitrile (B) as mobile phase with a flow rate of 0.3mlmin-1. Based on the spectral maxima, BRIM and its impurities were monitored at 248nm, and TIMO and its impurities were monitored at 295nm. During evaluation of stress conditions and stability data unknown degradants are observed and identified as m/z 218.01 (DP1) and m/z 390.03 (DP2) using QDa-ESI+ scanning mode technique. The performance of the method was systematically validated according to ICH Q2 (R1) guidelines and the method shown very good sensitivity (≥0.5µg.mL-1) and linearity (r2≥0.999) with consistent recoveries and less than 5% RSD for all compounds. Hence, the proposed UPLC/PDA/QDa method is a simple, sensitive and comprehensive technique where identification and quantification can be done. It gives for complete impurity profile evaluation of BRIM/TIMO in the ophthalmic formulation during quality control in the pharmaceutical industry.
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Timolol , Tartrato de BrimonidinaRESUMEN
Purpose: In this study, we wanted to retrospectively evaluate the effect of the use of topical brimonidine on intraoperative bleeding and surgical hemostasis before strabismus surgery. Methods: Brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops were applied 6 and 3 min before surgery to 44 eyes of 22 patients in group 1 for vasoconstriction. Drops were not applied to 46 eyes of 23 patients in group 2. Preoperative and postoperative photographs and video images were taken. Black-and-white images were used to define the surface areas of the blood vessels. The surface area was calculated by counting the black pixels with ImageJ software. Results: In group 1, redness of eye was observed, on average, at preoperative 339.25 ± 11.52 pixels and intraoperative 247.93 ± 10.63 pixels (P < 0.001). But there was no change in group 2 (preoperative 338.87 ± 8.45 pixels to intraoperative 339.71 ± 9.52 pixels, P > 0.05). The incidence of intraoperative bleeding evaluated by the number of eyes on which cautery was used shows that it was significantly less in group 1 than in group 2 (P < 0.001). Conclusions: The use of topical brimonidine before strabismus surgery facilitates clear monitoring of anatomical structures during surgery by effectively controlling hemorrhage. In the postoperative period, it significantly reduces subconjunctival hemorrhage.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Tartrato de Brimonidina/administración & dosificación , Complicaciones Intraoperatorias/epidemiología , Cuidados Preoperatorios/métodos , Estrabismo/cirugía , Administración Tópica , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/efectos adversos , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Tartrato de Brimonidina/efectos adversos , Tartrato de Brimonidina/farmacología , Estudios de Casos y Controles , Niño , Enfermedades de la Conjuntiva/epidemiología , Enfermedades de la Conjuntiva/patología , Hemorragia del Ojo/epidemiología , Hemorragia del Ojo/prevención & control , Femenino , Hemorragia/epidemiología , Hemorragia/prevención & control , Hemostasis Quirúrgica , Humanos , Hiperemia/inducido químicamente , Hiperemia/epidemiología , Hiperemia/prevención & control , Incidencia , Masculino , Soluciones Oftálmicas , Fotograbar/métodos , Periodo Posoperatorio , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: To assess the 12-month efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol maleate 0.5% (FCBT) with or without bimatoprost 0.01% (BIM) in primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG). STUDY DESIGN: Prospective, multicenter, open-label study. METHODS: FCBT was self-administered twice daily after applicable washout (study eye). Intraocular pressure (IOP) was measured at baseline and months 1, 3, 6, 9, and 12. BIM could be added for IOP ≥ 21 mmHg, IOP reduction from baseline < 20%, or the investigator deemed it necessary. Primary endpoint: mean (11-a.m.) month-12 IOP change from baseline. Secondary endpoints included mean IOP changes from baseline at other visits, median time to achieving and patients (%) achieving target IOP reduction with FCBT, and visual field (VF) progression rate over 12 months. Safety was assessed at each visit. RESULTS: Of 118 eyes with POAG (NTG, n = 93), 87 used FCBT; 31 required FCBT + BIM. Mean IOP changes from baseline (16.8 and 15.3 mmHg) to month 12 were - 4.1 mmHg (FCBT, n = 62) and - 3.5 mmHg (FCBT + BIM, n = 15), respectively (both P < 0.0001). Patients who achieved target IOP reduction with FCBT did so in 1 month (median). VF progression rates were 0.17%/year (FCBT, P = 0.8367) and - 0.08%/year (FCBT + BIM, P = 0.9410). Ocular treatment-emergent adverse events occurred in 42.5% (FCBT) and 71.0% (FCBT + BIM) of patients; most were mild and included ocular hyperemia (9.2% and 41.9%, respectively). CONCLUSIONS: Despite low mean baseline IOP, ≥ 20% IOP reduction from baseline persisted over 12 months with FCBT and FCBT + BIM, without clinically significant VF progression. Tolerability was consistent with reported drug safety profiles.