Timolol Research Articles

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

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

Preparation and Characterization of Instantly-soluble Solid Eye Drop for Glaucomatous Patients

For the treatment of glaucoma eye drops are chronically used. However, chronic use of preservatives in eye drops cause irritation problem and aff ects ocular tissues. The aim is to formulate an instant soluble solid eye drop to avoid using preservatives since solid dosage forms do not require preservation. Ocular mini-tablets of dorzolamide hydrochloride (DZ) and timolol maleate (TM) were prepared by direct compression using diff erent polymers and were evaluated for their physical properties. The release DZ and TM was compared to COSOPT eye drops. Formulation F2 mini-tablets (which contain DZ, TM, mannitol and microcrystalline cellulose MCC) were chosen as the optimum formula because they had uniform shape and minimum variation in weight 9.69 ± 0.55 mg. Thickness and diameter were 1.38 ± 1.28 and 3.01 ± 0.03 mm, respectively, within the acceptable limits. Hardness and friability were also within the permissable range which were 4.14 ± 0.22 kg/cm2 for hardness and 0.73% ± 0.05 for friability. The drug content for both DZ and TM were within the acceptable limits and the release had no signifi cant diff erence (p > 0.05) compared to commercial eye drop and the mini-tablets dissolved completely with less than one minute. The FTIR and DSC revealed no interaction between the drugs and excipients used. Sterilization using gamma radiation was performed to test the animal’s mini-tablets. The radiation did not signifi cantly (p > 0.05) alter any properties of F2 and no signs of irritation on the animal eye appeared. In conclusion, instant soluble solid eye drop in the form of mini-tablet was successfully prepared by direct compression method and caused no irritation when tested on animals

Prophylactic role of Timolol to prevent rise of intraocular pressure after Nd-YAG laser posterior capsulotomy

This study was conducted to know the effectiveness of topical 0.5% timolol maleate for the intraocular pressure rise after Nd-YAG laser posterior capsulotomy. Ninety-six eyes of 92 patients undergoing Nd-YAG laser posterior capsulotomy were randomly selected for pretreatment with topical 0.5% timolol maleate, 48 patients (Group A) or control 48 patients (Group B). The mean IOP of the group A was 14.8±3.0 mmHg before capsulotomy and 15.7±3.4 mmHg after capsulotomy (P >0.05), whereas 15.1±3.3 mmHg and 17.2±4.3 mmHg (P <0.05) of the group B. There was no statistically significant difference between the two groups with regard to mean IOP before capsulotomy (P >0.05), but statistically significant difference between two groups after capsulotomy (P <0.05). Pretreatment with topical 0.5% timolol maleate is effective in preventing IOP elevation after Nd-YAG laser posterior capsulotomy.

An eco-friendly separation-based framework for quantitative determination and purity testing of an antihypertensive ternary pharmaceutical formulation

Designing new, verified methodologies with a focus on sustainability, analytical efficiency, simplicity, and the environment has become a major priority for pharmaceutical quality control units. In this way, sustainable and selective separation-based methodologies were designed and validated for the concurrent estimation of amiloride hydrochloride (AML), hydrochlorothiazide (HCT) and timolol maleate (TIM) in their fixed dose formulation (Moducren® Tablets) along with hydrochlorothiazide potential impurities, salamide (DSA) and chlorothiazide (CT). The first method is a high performance thin layer chromatographic method (HPTLC-densitometry). The first developed method employed silica gel HPTLC F254 plates as stationary phase using a chromatographic developing system composed of ethyl acetate–ethanol–water–ammonia (8.5:1:0.5:0.3, by volume). The separated drug bands were densito-metrically measured at 220.0 nm for AML, HCT, DSA and CT and at 295.0 nm for TIM. The linearity was assessed over a wide concentration range, 0.5–10 µg/band, 1.0–16.0 µg/band and 1.0–14 µg/band for AML, HCT and TIM, in order and 0.05–1.0 µg/band for each of DSA and CT. The second method is capillary zone electrophoresis (CZE). The electrophoretic separation was achieved using background electrolyte (BGE), borate buffer 40.0 mM with pH 9.0 ± 0.2, at applied voltage of + 15 kV with on-column diode array detection at 200.0 nm. The method linearity was reached over the concentration range of 20.0–160.0 µg/mL, 10.0–200.0 µg/mL, 10.0–120.0 µg/mL for AML, HCT and TIM, respectively and 10.0–100.0 µg/mL for DSA. The suggested methods were optimized to achieve best performance and validated agreeing with the ICH guidelines. Assessment of methods’ sustainability and greenness was performed using different greenness assessment tools.Graphical

Ocular Pharmacokinetic Properties of Intravitreally Injected Aflibercept in Rabbits After Using Brinzolamide/Timolol Eye Drops.

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.

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

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

Poly(Sulfobetaine Methacrylate-co-Vinyl Pyrrolidone) Hydrogels as Potential Contact Lenses Delivery Systems for Timolol Maleate

The study reveals the development of novel hydrogels based on sulfobetaine methacrylate (SB) and vinyl pyrrolidone (VP) copolymers as potential contact lenses delivery systems of timolol maleate (TM). The novel copolymer networks demonstrated composition dependent swelling kinetics, where the hydrophilicity of VP and the physical network of SB monomeric units play significant roles. TM loading efficiency appeared to slightly depend on the copolymeric composition, increasing upon VP monomeric unit increase. In contrast, the TM release was prolonged when the SB monomeric units content in the copolymers increased, reaching full drug release for 48 h for the SB-rich networks. The transparency of the hydrogels was also studied and the obtained values demonstrate their applicability as potential materials for soft contact lenses. The study has revealed the potential of these novel copolymeric hydrogels as materials for contact lenses delivery systems of timolol maleate.

Eco-friendly chromatographic platforms for simultaneous determination and impurity profiling of an antihypertensive ternary pharmaceutical mixture

Development of new analytical methods that are capable of determining pharmaceutically active substances in the presence of their related impurities is vital in pharmaceutical industry. Herein, simple, reliable and ecofriendly chromatographic methods were established, optimized and validated for the concurrent estimation of amiloride hydrochloride (AML), hydrochlorothiazide (HCT) and timolol maleate (TIM) along with hydrochlorothiazide potential impurities, salamide (DSA) and chlorothiazide (CT). The first established method was based on high performance liquid chromatography (HPLC-DAD). Separation was achieved using XBridge C18 analytical column and a gradient elution system comprises solvent A [20.0 mM phosphate buffer (pH = 3)] and solvent B [acetonitrile]. UV detection was accomplished at 220.0 nm for AML, HCT and HCT related impurities and at 295.0 nm for TIM. The second method was a LC-MS/MS method for the profiling and quantification of HCT impurities (DSA and CT). Separation was executed on Agilent Poroshell 120 EC-C18 column using mobile phase consisted of methanol and 0.1% formic acid in a ratio of 97:3 (v/v) pumped at flow rate of 0.7 mL/min with a run time of 3.0 min. Impurities were quantified via the utilization of multiple reaction monitoring mode (MRM) and triple quadrupole mass detection with electrospray ionization. The method demonstrated excellent sensitivity and linearity with limit of detection (LOD) of 1.0 ng/mL and 0.1 ng/mL for DSA and CT, respectively. Validation of the suggested methods was achieved in compliance with the ICH guidelines and were successively utilized for the determination of the aformentioned compounds in Moducren® tablets. Additionally, the advantage of the developed HPLC-DAD method was extrapolated for in-vitro drug release monitoring. Greenness of the proposed methods was assessed using different well established assessment tools.

Two Stability Indicating Chromatographic Methods: TLC Densitometric versus HPLC Method for the Simultaneous Determination of Brinzolamide and Timolol Maleate in Ophthalmic Formulation in the Presence of Probable Carcinogenic Oxidative Degradation Product of Timolol Maleate

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.

Oralni topikalni timolol maleat ili oralni propranolol u lečenju infantilnih hemangioma: klinička analiza 403 pacijenta

Objective: Infantile hemangiomas (IH) are the most common benign vascular tumors of infancy. Propranolol (P), a nonselective beta-blocker, has been successfully used in managing IHs. Ongoing studies investigate the efficacy of the topical b-antagonist timolol maleate (TM) in IHs. The aim of this study is to assess the effects of interventions for managing infantile hemangiomas in children. Material and Methods: We retrospectively reviewed a total of 403 IH patients from March 2021 to March 2022. The patients were stratified into three groups. Patients in Group 1 were given TM at a dose of one drop topically twice a day, 0.5%. Patients in Group 2 were given P at a dose of 1 mg/kg twice a day. The patients in Group 3 did not receive any treatment, and observation was conducted solely by contacting the controls. Results: The median age of diagnosis was 5 months (range 0-60), with 57.1% of the cases being male. While TM treatment was applied to 32% of the children and P treatment was applied to 46.9% of the children, no treatment was administered in 21.1%. The most common location of hemangiomas was the face, accounting for 39.2%. Hemangiomas were observed in more than one location in 48 (12%) children. The median follow-up period for the patients was 4 months (range 0-28). Hemangiomas remained unchanged in 28.3% of all cases, shrank in 60.3%, and continued to grow in 11.4%. The primary indication for initiating TM was superficial hemangiomas and infants younger than 6 months. The leading reason for starting P significantly higher than in the other groups (p : 0.001). No statistically significant differences were observed between the groups regarding bleeding and ulceration rates (p > 0.05). Conclusion: The efficacy of propranolol in treating IH was higher than that of TM.

Effect of 32P Application Combined with Timolol Maleate on Circulating Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Children with Cutaneous Hemangioma

Effect of 32P Application Combined with Timolol Maleate on Circulating Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Children with Cutaneous Hemangioma

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

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

Design and characterization of Timolol maleate and Travoprost hydrogel drug delivery system

Design and characterization of Timolol maleate and Travoprost hydrogel drug delivery system

Pyogenic Granuloma Treated with Topical Timolol: A Case Series

Pyogenic Granulomas (PGs) are benign vascular tumours primarily treated with surgical procedures. Recently, topical Timolol, a beta-adrenergic receptor antagonist, has been used for the treatment of PG due to its vasoconstrictive, anti-angiogenic, and wound healing properties. Herein, the authors presented a case series of 12 patients (10 males and two females) with red papules and nodules that spontaneously bleed. The age of the patients ranged from 7-51 years, and the duration of lesions ranged from one week to nine months. The lesions were located on the face, neck, hand, and mucosa. All patients were treated with topical Timolol maleate 0.5% drops twice daily for four weeks and followed-up weekly for four weeks. The treatment efficacy was evaluated based on complete response, partial response, or no response. Changes in colour, size, bleeding tendency, and adverse events were also assessed. Two patients showed complete resolution, while the bleeding tendency improved in the other patients. No side effects were encountered, except in one patient where the lesion increased in size and became secondarily infected. Thus, topical timolol appeared to provide symptomatic improvement by reducing bleeding and lesion size without any side effects. It can be considered as an alternative therapeutic option for small, uncomplicated classical PG.

Forced degradation of timolol maleate on high temperature for verification of HPLC method for related substances in Timolol eye drop 0.5%

Forced degradation of timolol maleate on high temperature for verification of HPLC method for related substances in Timolol eye drop 0.5%

Inkjet drug printing onto contact lenses: Deposition optimisation and non-destructive dose verification

Inkjet printing has the potential to advance the treatment of eye diseases by printing drugs on demand onto contact lenses for localised delivery and personalised dosing, while near-infrared (NIR) spectroscopy can further be used as a quality control method for quantifying the drug but has yet to be demonstrated with contact lenses. In this study, a glaucoma therapy drug, timolol maleate, was successfully printed onto contact lenses using a modified commercial inkjet printer. The drug-loaded ink prepared for the printer was designed to match the properties of commercial ink, whilst having maximal drug loading and avoiding ocular inflammation. This setup demonstrated personalised drug dosing by printing multiple passes. Light transmittance was found to be unaffected by drug loading on the contact lens. A novel dissolution model was built, and in vitro dissolution studies showed drug release over at least 3 h, significantly longer than eye drops. NIR was used as an external validation method to accurately quantify the drug dose. Overall, the combination of inkjet printing and NIR represent a novel method for point-of-care personalisation and quantification of drug-loaded contact lenses.

Container closure selection and stability studies of developed multistimuli-responsive ocular sustained in situ hydrogel formulation of timolol maleate

Container closure selection and stability studies of developed multistimuli-responsive ocular sustained in situ hydrogel formulation of timolol maleate

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

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

Serum Lipid Profiles of Primary Open Angle Glaucoma Patients Treated with Topical Timolol

Background: Primary open-angle glaucoma (POAG) and atherosclerosis both are fairly common diseases among elderly persons, any adverse changes in serum lipids as a result of glaucoma therapy can increase the risk of coronary heart disease many folds. As topical beta blockers are also widely used and often the first line therapy in many patients requiring treatment for glaucoma for a long time, there is also a possible risk that _-blockers such as timolol adversely affect serum lipid profiles.&#x0D; Objective: The study aimed to evaluate the effect of topical timolol on serum lipid profiles.&#x0D; Methods: This cross-sectional observational study was performed in the department of ophthalmology, Bangabandhu Sheikh Mujib Medical University With convenience type of sampling technique 40 patients with newly diagnosed cases of primary open-angle glaucoma were selected. Baseline fasting lipid profiles were estimated and then timolol maleate 0.5%, 1 drop 12 hourly in both eyes were prescribed. At follow-up after 4 and 12 weeks, again fasting lipid profiles were estimated of the same patients.&#x0D; Results: In this study the baseline mean TC, HDL, LDL &amp; TG were 175.4±19.28 , 46.63±5.33, 104.98±18.49,120.48±28.30 (mg/dl±SD) respectively. Baseline TC/HDL was 3.81±0.06. At follow up after 4 weeks there were increased level of TC, LDL,TG, TC/HDL by 0.45% (P=0.822), 0.8% (P=0.807) 1.82%(P=0.375), and 3.14%(P=0.307) respectively and HDL level decreased by 2.68%(P=0.232). At follow-up, after 12 weeks in comparison to baseline lipid levels, there was an increased level of TC, LDL, TG, and TC/HDL by 0.98% (P=0.959), 3% (P=0.996), 2.8% (P=0.104), and 17.0%(P=0.001) respectively and HDL level decreased by 13.61%(P=0.001).&#x0D; Conclusion: Topical timolol significantly lowers the plasma HDL level. Since the low level of HDL is strongly associated with an increased risk of myocardial infarction, our study cautions against the use of timolol in patients with a previous history of coronary heart disease.&#x0D; J Rang Med Col. September 2022; Vol. 7, No. 2:40-46

A novel fixed-combination timolol-netarsudil-latanoprost ophthalmic solution for the treatment of glaucoma and ocular hypertension

Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration, poor efficacy and side effects. Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution (FC-TNL) has the ability to treat glaucoma by lowering the intraocular pressure (IOP) with great efficacy and improving patient compliance. However, the commercialized netarsudil dimesylate precipitated when the pH of the solution was above 5.4, or when maleic acid, the salt of commercial timolol maleate, was mixed with netarsudil dimesylate. Consequently, the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in pH 4.8–5.2 solution by synthesizing timolol mesylate. Next, the morphology of timolol mesylate was observed by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction. The prepared FC-TNL showed good stability during refrigeration storage. Additionally, FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study. Importantly, once-daily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells. The FC-TNL was stable, safe and effective, being a promising glaucoma therapeutic.