Timolol Research Articles

Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2.

Sepetaprost 0.002% Noninferiority vs. Timolol 0.5% in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: ANGEL-2.

Enhancing quality-by-design through weighted goal programming: a case study on formulation of ultradeformable liposomes

Introduction Optimization of pharmaceutical formulations requires advanced tools to ensure quality, safety, and efficacy. quality-by-design (QbD), introduced by the FDA, emphasizes understanding and controlling processes early in development. Advanced optimization methods, such as desirability, have surpassed traditional single-objective techniques. Others, such as weighted goal programming (WGP) offers unique advantages by integrating decision-maker preferences, enabling balanced solutions for complex drug delivery systems. This study applies WGP to optimize timolol (TM)-loaded nanoliposomes aligning with QbD principles. Methods The optimization process followed six steps: identifying factors and responses, developing a Design of Experiments (DoE) plan, defining ideal and anti-ideal points, setting aspiration levels, assigning relative weights, and applying WGP compared to desirability function. Minimized and balanced deviations from aspiration levels served as criteria for selecting the most robust optimization results. Six responses were analyzed: vesicle size ( z 1 ) , polydispersity index ( z 2 ) , zeta potential ( z 3 ) , deformability index ( z 4 ) , phosphorus content ( z 5 ) , and drug entrapment efficiency ( z 6 ) . Results WGP produced a more balanced formulation that simultaneously optimized multiple responses. By incorporating the importance of each response, the WGP approach improved control over size, colloidal stability, and drug entrapment, based on its mathematical formulation. Comparative analysis with the desirability function confirmed that WGP effectively addressed potential tradeoffs without oversimplifying conflicting objectives. Conclusions This case-study demonstrates WGP potential as an advanced multi-objective optimization tool for pharmaceutical applications, improving upon traditional methods in complex formulations. Its ability to harmonize multiple critical attributes in line with QbD highlights its value in developing high-quality pharmaceutical products.

Thiolated gellan gum/polyethylene glycol diacrylate hydrogels containing timolol maleate-loaded chitosan nanoparticles for ophthalmic delivery

The combination of hydrogels with nanoformulations can significantly enhance the delivery and effectiveness of drugs in ophthalmic drug delivery systems. In the current study, the polyethylene glycol diacrylate (PEGDA)/thiolated gellan gum (GGSH) hydrogels based on GGSH and PEGDA were prepared via thiol-ene reaction using Irgacure 2959 as a photoinitiator. To this end, the modification of GG was achieved by esterification of the hydroxyl groups of GG with the carboxyl group of mercaptopropionic acid with a free thiol amount of 95.5 μmol g-1. To provide sustained release, chitosan nanoparticles (CSNPs) containing timolol maleate (TM) with 56.4% entrapment efficiency were synthesized by the desolvation method and encapsulated in the developed hydrogel. The values of zeta potential and particle size of CSNPs were +26.0 mV and 182.4 nm, respectively. The physico/chemical properties of the hydrogels were investigated via texture analyzer, FT-IR, XRD, and SEM. Thein vitrodegradation, swelling behavior, rheological assessments, cell viability testing, and porosity determination were evaluated. With the increase in PEGDA concentration, the mechanical properties were increased. While the rate of swelling, degradation, and drug release were decreased. Thein vitrobiocompatibility of hydrogels was confirmed using the MTT test. According to anex vivostudy, ocular drug delivery using the obtained transparent hydrogels is promising due to improved drug permeation and sustained release of TM via CSNPs.

Treatment of glaucoma with drug-loaded contact lenses: A systematic review and meta-analysis.

Treatment of glaucoma with drug-loaded contact lenses: A systematic review and meta-analysis.

Simultaneous determination of brinzolamide, timolol maleate and its oxidative degradation product using univariate and multivariate green spectrophotometric methods

Simultaneous determination of brinzolamide, timolol maleate and its oxidative degradation product using univariate and multivariate green spectrophotometric methods

A water-soluble drug nanoparticle-loaded in situ gel for enhanced precorneal retention and its transduction mechanism of pharmacodynamic effects.

A water-soluble drug nanoparticle-loaded in situ gel for enhanced precorneal retention and its transduction mechanism of pharmacodynamic effects.

Efficacy and safety of combined fractional carbon dioxide laser and topical timolol maleate 0.5% solution versus topical timolol maleate 0.5% solution alone in inflammatory facial acne; a randomized split face controlled study.

In this study, we aimed to investigate the efficacy and safety of combined fractional carbon dioxide laser and topical timolol maleate 0.5% solution versus topical timolol maleate 0.5% solution alone in inflammatory acne. Thirty adult patients with inflammatory facial acne were randomized in this study. The patients received 3 biweekly sessions of fractional CO2 laser on one side of the face followed by topical timolol maleate ophthalmic solution 0.5% once daily for 7 days on both sides. Outcome was evaluated 2 weeks after the first session, 2 weeks after the last session, and 1 month after the last session by lesion count, erythema, hyperpigmentation, qualitative global scarring grading, and patients' satisfaction. Side effects were also evaluated. Trial registration (IRB No. 417, 30/10/2023). At 2 weeks after the first session, there were insignificant differences between both sides regarding lesion count, erythema, hyperpigmentation, and qualitative global scarring grading (p value = 0.8, 0.05, 0.7, 0.1 respectively). At 2 weeks after the last session, the erythema on the combined side was reduced by a mean of 0.2 ± 0.4 SD compared to timolol only side with significant difference between both sides (p value = 0.03), while there were insignificant differences between both sides regarding lesion count, hyperpigmentation, qualitative global scarring grading, and patients' satisfaction (p value = 0.1, 0.5, 0.8, 0.3 respectively). Recurrence was detected at one month after the last session. No side effects were reported. Combined fractional CO2 laser and topical timolol maleate 0.5% solution were significantly more effective than topical timolol maleate 0.5% solution alone in reduction of erythema of inflammatory facial acne in adolescent men with Fitzpatrick's skin type III-IV at 2 weeks after 3 biweekly sessions with insignificant differences between both sides regarding lesion count, hyperpigmentation, qualitative global scarring grading, and patients' satisfaction. Further and larger studies are still needed.

Synthesis and Characterization of 3-S-impurities in Timolol Maleate.

Timolol maleate is clinically used for the treatment of hypertension, angina pectoris, tachycardia, and glaucoma. The aim of this study was to enhance the safe use of timolol maleate and investigate a synthesis method for 3-S-timolol, a newly identified impurity in timolol API (Active Pharmaceutical Ingredients). (S)-3-(tert-butylamino)propane-1,2-diol (1) was used as a raw material. 3-S-timolol maleate (7) was synthesized through a five-step reaction. Overall yield was 57.7%, with a purity of 98%. The structure of the target compound was confirmed via analysis of its 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry spectra. The synthesis method was straightforward and yielded a high-purity product suitable for use as a reference in the analysis and identification of timolol maleate-related substances.

Development and statistical optimization of timolol maleate encapsulated liposome using 32 full factorial design

Development and statistical optimization of timolol maleate encapsulated liposome using 32 full factorial design

Herpetic Endotheliitis Induced Interface Fluid Syndrome 16 years After Laser in Situ Keratomileusis.

To report a case of herpes simplex virus (HSV) endotheliitis inducing acute interface fluid syndrome in a patient with a remote history of laser in situ keratomileusis (LASIK). Case report and literature review. A 51-year-old man with a history of LASIK 16 years prior presented with unilateral HSV endotheliitis and was found to have acute interface fluid syndrome secondary to endothelial decompensation. The patient was treated with oral valacyclovir 1 g 3 times daily, prednisolone acetate 1% drops 4 times daily, timolol maleate 0.5% drops twice daily, topical 5% sodium chloride hypertonic ophthalmic solution drops 4 times daily, and 5% sodium chloride hypertonic ophthalmic ointment nightly. At 1-month follow-up, the patient had full resolution of the interface fluid and returned to baseline visual acuity. This case underscores the importance of considering viral etiologies, such as HSV endotheliitis, in interface fluid syndrome beyond a decade after LASIK.

Development and Evaluation of Polymethacrylate-Based Ophthalmic Nanofiber Inserts Containing Dual Drug-Loaded Dorzolamide and Timolol: In Vivo Study in Rabbit's Eye.

Background/objectives: The aim of the study was to create a nanofiber insert incorporating Timolol (TIM) and Dorzolamide (DOR), targeting the management of glaucoma. This condition encompasses a variety of chronic, advancing ocular disorders typically associated with elevated intraocular pressure (IOP). Methods: The insert was made of Eudragite RL100 (EUD) polymer, a biocompatible material with high bioavailability, using the electrospinning method. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, and in vitro drug-release study. The pharmacokinetic properties of fibers were examined alongside consideration for irritation using a rabbit model and cell compatibility. Results: The results of the in vitro drug-release test showed retention and controlled release of both DOR/TIM over 80 h. Morphological examination demonstrated uniform nanofibers with mean diameters < 465 nm. The cell compatibility test showed a high percentage of cell survival, and none of the formulations irritated the rabbit's eye. The Area Under the Curve (AUC0-72) for DOR and TIM in EDT formulations was approximately 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with Mean Residence Times (MRTs) of approximately 21.6 ± 0.19 h and 16.29 ± 6.44 h. Conclusions: Based on the results, the dual drug-loaded nanofiber preservative-free system can potentially be a suitable alternative to eye drops and can be used to reduce fluctuation and dose frequency.

Colloid-Forming Prodrug-Hydrogel Composite Prolongs Lower Intraocular Pressure in Rodent Eyes after Subconjunctival Injection.

Colloidal drug aggregates (CDAs) are challenging in drug discovery due to their unpredictable formation and interference with screening assays. These limitations are turned into a strategic advantage by leveraging CDAs as a drug delivery platform. This study explores the deliberate formation and stabilization of CDAs for local ocular drug delivery, using a modified smallmolecule glaucoma drug. A series of timolol prodrugs are synthesized and self-assembled into CDAs. Of four prodrugs, timolol palmitate CDAs have a critical aggregate concentration of 2.72µM and sustained in vitro release over 28 d. Timolol palmitate CDAs are dispersed throughout in situ gelling hyaluronan-oxime hydrogel and injected into the subconjunctival space of rat eyes. The intraocular pressure is significantly reduced for at least 49 d with a single subconjunctival injection of timolol-palmitate CDAs compared to 6h for conventional timolol maleate. The systemic blood concentrations of timolol are significantly lower, even after 6h, for timolol palmitate CDA-loaded hydrogel versus free timolol maleate, thereby potentially reducing the risk of systemic side effects. This innovative approach redefines the role of CDAs and provides a framework for long-acting ocular therapeutics, shifting their perception from a drug screening challenge to a powerful tool for sustained local drug delivery.

Review of the Synthesis of Timolol Maleate and Brimonidine Tartrate Drug Substances Used for the Treatment of Open-Angle Glaucoma

Review of the Synthesis of Timolol Maleate and Brimonidine Tartrate Drug Substances Used for the Treatment of Open-Angle Glaucoma

Unexpected airway bleed: A rare case of hemoptysis triggered by topical beta-blocker use

Timolol, a non-selective beta-adrenergic antagonist and commonly used intra-ocular pressure lowering agent, acts by reducing the formation of aqueous humor by acting on the beta 2 receptors in the ciliary epithelium. Its common ocular side effects include burning, stinging, irritation, dryness, itching, watering, conjunctival hyperemia, lid edema, blurring of vision, dry eye, etc. Systemic side effects include bronchospasm, bronchoconstriction, wheezing, chest pain, bradycardia, muscle weakness, depression, fatigue, confusion, hair loss, disorientation, increased low-density cholesterol levels, headache, dizziness, etc. Since the drug has a significant range of adverse effects, it is important to monitor the patients to detect the side effects early and manage them appropriately. Here, we present an unusual case of hemoptysis precipitated by timolol which led to the discovery of underlying Koch’s sequelae. To the best of our knowledge, this is the first case of such a rare side effect of topical timolol maleate (0.5%) ophthalmic solution.

Economic impact of initial glaucoma treatment with selective laser trabeculoplasty on the Brazilian Public Health System.

To evaluate the economic impact of the following initial treatment scenarios for glaucoma on the Brazilian Public Health System (SUS): (1) traditional continuous instillation of hypotensive eye drops and (2) single session of selective laser trabeculoplasty. Economic impact was analyzed in three scenarios, from the least to the most conservative, for a hypothetical cohort of 5,000 individuals with open-angle glaucoma. Thereafter, projections were made on the basis of a glaucoma prevalence of 3% in the 2021 Brazilian population size. All three scenarios demonstrated that selective laser trabeculoplasty exhibited a significantly lower economic impact than the eye drops on SUS over one and five years. Furthermore, the difference was more than United States Dollar 8 billion at five years when considering 3% of the Brazilian population aged >40 years in 2021. As the initial treatment for primary open-angle glaucoma, selective laser trabeculoplasty exhibited a lower economic impact on SUS than latanoprost and timolol maleate eye drop instillation in all the studied scenarios over one and five-year periods.

Molecular Imprinted Hydrogels for the Controlled and Sustained Release of Hydrophilic Drug Therapy.

Hydrogels can be used in many biomedical applications and can be imprinted with hydrophilic target molecules through hydrogen bonding. The imprinting process leaves a void space within the hydrogel matrix that includes both the shape and the functionality of the target molecules, thus enabling a thermodynamically favorable interaction between the target molecules and the hydrogel matrix. Our laboratory has developed a standard method for imprinting hydrophilic drug molecules into the hydrogel structure. While applications may include both drug delivery and signal recognition in chemical sensors, we report here on applications in drug delivery and the therapeutic treatment of ocular diseases by utilizing timolol maleate as the target molecule. Here, we describe the protocols we have developed for the preparation of molecular imprinted hydrogels for use in drug delivery applications.

Preparation, In-Vitro and Ex-Vivo Evaluation of Liposomal Gel Delivery system for Timolol Maleate

Preparation, In-Vitro and Ex-Vivo Evaluation of Liposomal Gel Delivery system for Timolol Maleate

Evaluation of binocular once only instillation of timolol maleate 0.5% eye drop for treatment of presbyopia

Introduction: When beta 2 mediated relaxing effect on ciliary muscle is blocked by Timolol maleate 0.5% eye drop, then there is increase of tonic accommodation, thus presbyopia is corrected. Therefore purpose of this placebo controlled trial is to determine and compare the near point of accommodation and amplitude of accommodation of the subjects before and after instillation of Timolol maleate 0.5% eye drop.Materials and Methods: After getting approval from the Institutional ethics committee, and informed consent,we recruited 40 emmetropic subjects (80 eyes) of ages between 35-45 years, and randomly assigned them to binocular once only instillation of one drop of Timolol maleate 0.5% eye drop (intervention group, 20 subjects) or Normal saline eye drop (Control group, 20 subjects). Near points of Accommodation (NPA) were measured in these 40 subjects by RAF rule prior to giving eye drop and then at half hourly interval after instillation till effect started to wean off.Statistical analysis: The statistical software SPSS version 25 was used for the analysis.Study design: Prospective assessor masked, randomised controlled interventional study.Results: We found that the effect on NPA started to wean off after 8 hrs. However after an initial steady fall between 1-4 hr, NPA maintained a steady state between 4-8 hrs of instillation at points closer to eye by an average of 5.79 +/- 2.87cm (P &lt; 0&gt; Conclusion: One drop of Timolol maleate 0.5% eye drop instilled binocularly can achieve correction of presbyopia to the tune of + 1.21 +/- 0.42 Dioptre, sustained for 4 hrs between 4 and 8 hrs after instillation.

Timolol Maleate Microspheres: An Ingenious Carrier for Sustained Release Antihypertensive Formulation

Background: Timolol maleate is classified as a BCS Class I drug and functions as a non-selective β-adrenergic receptor blocker. Its ability to lower heart rate and cardiac output has led to its widespread use in the treatment of hypertension. Objective: Timolol maleate has a short half-life and is rapidly cleared from the body, which limits its therapeutic effectiveness, requiring frequent dosing and potentially affecting patient adherence. To overcome these challenges, sustained-release microspheres of Timolol maleate were developed using the ion gelation method. Method: The ion gelation technique was employed to create the microspheres due to its various advantages, including ease of use, scalability and gentle processing conditions. Results: All batches exhibited a comparatively lower swelling index in 0.1M HCl (pH 1.2) than in SIF (pH 6.8). It was observed that increasing the concentration of sodium alginate resulted in higher drug content. The microspheres were sized between 400 and 900 μm and demonstrated excellent flow characteristics. An optimized batch achieved an entrapment efficiency of 88.83% and released 92.15% of the drug over 7 hrs. Furthermore, stability studies conducted according to ICH Q1A(R2) for 3 months at 5±3°C and 25±2°C/60±5% RH indicated no significant changes in evaluation parameters. Conclusion: The optimized Timolol maleate-loaded microspheres effectively provided sustained drug release through the membrane over 7 hrs. This study contributes to the development of improved drug delivery systems for better hypertension management, addressing the unmet needs in patient compliance. Keywords: Timolol Maleate, Microspheres, Ion gelation method, Sodium alginate, Calcium chloride, Sustained release, Hypertension

Evaluating the greenness, blueness, and whiteness of spectroscopic and UPLC techniques for the simultaneous measurement of anti-glaucoma drugs and the preservation agent

Evaluating the greenness, blueness, and whiteness of spectroscopic and UPLC techniques for the simultaneous measurement of anti-glaucoma drugs and the preservation agent