An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper.

PURPOSE: To examine if 12.5 µl timolol maleate 0.5% microdrops dispensed with the Nanodropper Adaptor provide noninferior intraocular pressure (IOP) reduction compared with conventional 28 µl drops in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). DESIGN: Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. PARTICIPANTS: Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. METHODS: Both eyes of subjects received 1 commercially available drop or both eyes of subjects received 1 microdrop of timolol maleate 0.5%. We measured IOP, resting heart rate (HR), and blood pressure (BP) at baseline and 1, 2, 5, and 8 hours after timolol administration. MAIN OUTCOME MEASURES: The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). RESULTS: Adaptor-mediated microdrops and conventional drops of timolol significantly decreased IOP compared with baseline at all timepoints. Noninferiority was established at 3 of 4 timepoints. Heart rate decreases with Nanodropper were approximately 3 beats per minute (bpm) less than with conventional drops. CONCLUSIONS: Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Chitosan nanoparticles laden contact lenses for enzyme-triggered controlled delivery of timolol maleate: A promising strategy for managing glaucoma.

To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 µg/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage.

Clinical study of timolol maleate combined with cryotherapy for infantile cutaneous hemangioma / 局解手术学杂志

Objective To explore the clinical effect of timolol maleate combined with cryotherapy for infantile cutaneous hemangioma.Methods A total of 240 infants with cutaneous hemangioma were randomly divided into the control group(120 cases)and the combined group(120 cases).The control group was treated with timolol maleate,and the combined group was treated with timolol maleate combined with cryotherapy.The clinical efficacy,tumor diameter,levels of serum matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)and the occurrence of adverse reactions of the two groups were compared.Results The total effective rate of the combined group was significantly higher than that of the control group(P<0.05).Compared with before treatment,the tumor diameter 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the tumor diameter 3 months and 6 months after treatment in the combined group decreased more obviously(P<0.05).Compared with before treatment,the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the two groups gradually decreased(P<0.05),and the levels of serum MMP-9 and VEGF 3 months and 6 months after treatment in the combined group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the total incidence of adverse reactions such as eczema,ulcer,erosion or redness between the two groups(P>0.05).Conclusion Timolol maleate combined with cryotherapy for infantile cutaneous hemangioma has significant curative effect,which can effectively reduce the levels of serum MMP-9 and VEGF,and shrink the tumor body,with safety and effectiveness.

Synthesis of novel interpenetrated network for ocular co-administration of timolol maleate and dorzolamide hydrochloride drugs.

In the present work, novel interpenetrated networks (IPNs) of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide) (SBMA) and poly(vinyl alcohol) (PVA) were prepared for the ocular co-administration of timolol maleate (TIM) and dorzolamide hydrochloride (DORZ), two drugs widely used for the treatment of glaucoma. The successful polymerization of SBMA, in the presence of PVA, led to the formation of semi-interpenetrated pSBMA-PVA networks (IPNs), in the form of sponges, exhibiting intrinsic antimicrobial properties attributed to SBMA. Fourier-transform infrared spectroscopy (FTIR) was utilized to confirm the successful synthesis of the IPNs. Further assessments, including contact angle and water sorption measurements, highlighted their significant hydrophilicity, a feature that makes them suitable for ocular applications. Differential scanning calorimetry (DSC) measurements indicated that PVA serves as a plasticizer, while an assessment of the water sorption capacity of these materials suggested that although the incorporation of PVA results in slightly less hydrophilic materials, the prepared sponges still remain sufficiently hydrophilic for ocular use. Following their characterization, the optimal pSBMA-PVA IPN was used to encapsulate TIM and DORZ. Irritation tests, performed using the HET-CAM method, confirmed that the drug-loaded sponges were safe and potentially well-tolerated for ophthalmic use. Finally, the co-release study for the two drugs revealed a sustained release pattern in both cases, while drug release from the sponges was primarily controlled by diffusion.

RNA-seq analysis of human trabecular endothelial cells after treatment with timolol maleate.

PURPOSE: Timolol maleate (timolol), a ß-receptor blocker, reduces intraocular pressure by decreasing aqueous humor production. Timolol reportedly also protects ganglion cells, decreases aqueous humor outflow facility, and destroys the extracellular matrix in the trabecular meshwork. In this study, we investigated the effects of timolol on cultured human trabecular endothelial cells purchased from ScienCell using next-generation sequencing. STUDY DESIGN: Experimental investigation. METHODS: Total ribonucleic acid (RNA) was extracted after 24 h. More than 100 million RNAs in control and timolol-treated group were sequenced using a next-generation sequencer. The expression of 55,778 RNAs was analyzed. RESULTS: A total of 2,105 genes were significantly upregulated and 2,125 genes were downregulated, after the addition of timolol. VGF nerve growth factor inducible (VGF) (388-fold) had the maximum increase in expression, followed by amphiregulin (333-fold), a member of the epidermal growth factor family. Moreover, the expression of extracellular matrix-degrading enzymes, matrix metalloproteinases (MMPs) 1, 2, 3, 10, 12, and 14, increased. CONCLUSION: Timolol exerts various effects on human trabecular endothelial cells. The increase in MMP expression may contribute to the decrease in the aqueous humor outflow facility.

Timolol-loaded ethosomes for ophthalmic delivery: Reduction of high intraocular pressure in vivo.

The beta-adrenoceptor blocker timolol maleate (TML) is a commonly used pharmaceutical agent for the management of glaucoma. Conventional eye drops have limitations due to biological or pharmaceutical factors. Therefore, TML-loaded ethosomes have been designed to mitigate these restrictions and give a viable solution for reducing elevated intraocular pressure (IOP). The ethosomes were prepared using the thin film hydration method. Integrating the Box-Behnken experimental strategy, the optimal formulation was identified. The physicochemical characterization studies were performed on the optimal formulation. Then, in vitro release and ex vivo permeation studies were conducted. The irritation assessment was also carried out with Hen's Egg Test-Chorioallantoic Membrane model (HET-CAM), and in vivo evaluation of the IOP lowering effect was also performed on rats. The physicochemical characterization studies demonstrated that the components of the formulation were compatible with each other. The particle size, zeta potential, and encapsulation efficiency (EE%) were found as 88.23 ± 1.25 nm, -28.7 ± 2.03 mV, and 89.73 ± 0.42 %, respectively. The in vitro drug release mechanism was found as Korsmeyer-Peppas kinetics (R2 = 0.9923). The HET-CAM findings verified the formulation's eligibility for biological applications. The IOP measurements revealed no statistical difference (p > 0.05) between the once-a-day application of the optimal formulation and the three-times-a-day application of the conventional eye drop. A similar pharmacological response was observed at lowered application frequencies. Therefore, it was concluded that the novel TML-loaded ethosomes could be a safe and efficient alternative for glaucoma treatment.

Synthesis and evaluation of modified lens using plasma treatment containing timolol-maleate loaded lauric acid-decorated chitosan-alginate nanoparticles for glaucoma.

Reducing intraocular pressure (IOP) with eye drops is one of the most common ways to control glaucoma. Low bioavailability and high frequency of administration in eye drops are major challenges in ocular pharmacotherapy. Contact lenses have attracted the attention of scientists in recent decades as an alternative method. In this study, with the aim of long-term drug delivery and better patient compatibility, contact lenses with surface modification and nanoparticles were used. In this study, timolol-maleate was loaded into polymeric nanoparticles made of chitosan conjugate with lauric acid and sodium alginate. Then silicon matrix was mixed with a curing agent (10:1), and the suspension of nanoparticles was added to the precursor and cured. Finally, for surface modification, the lenses were irradiated with oxygen plasma at different exposure times (30, 60, and 150 s) and soaked in different BSA concentrations (1, 3, and 5% w/v). The results showed nanoparticles with a size of 50 nm and a spherical shape were synthesized. The best surface modification of the lenses was for 5 (% w/v) albumin concentration and 150 s exposure time, which had the highest increase in hydrophilicity. Drug release from nanoparticles continued for 3 days and this amount increased to 6 days after dispersion in the modified lens matrix. The drug model and kinetic study show the Higuchi model completely supported the release profile. This study represents the novel drug delivery system to control intra-ocular pressure as a candidate platform for glaucoma treatment. Improved compatibility and drug release from the designed contact lenses would prepare new insight into the mentioned disease treatment.

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.

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.

Intraluminal deposits: A rare cause of glaucoma drainage implant total obstruction.

PURPOSE: To report the unforeseen complication of total obstruction of a glaucoma drainage implant (GDI) tube lumen by white deposit material and to present a preliminary report identifying the composition of this material. METHODS: Two subjects with a high IOP due to total obstruction of a GDI tube were reviewed. Both patients had a long history with brinzolamide and timolol maleate eye drops. The GDI tube was swept with a 5-0 polypropylene suture stent in order to open the tube. The intraluminal solid sample was successfully collected from the implant tube in one patient. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was used to determine the origin of the intraluminal sample. RESULTS: Intraluminal deposits containing components of antiglaucoma drugs e.g., timolol and brinzolamide are a rare cause of total obstruction of GDI tubes. CONCLUSIONS: Our study describes a new cause of total obstruction GDI tubes. The long-term use of timolol maleate and brinzolamide and their presence in the intraluminal solid sample collected from the blocked GDI tube suggest that the glaucoma medication may have a role in the pathogenesis. However, the exact mechanism is unknown and requires further studies.

Development and evaluation of polycaprolactone-based electrospun nanofibers containing timolol maleate as a sustained-release device for treatment of glaucoma: in vivo evaluation in equine eye.

Background and purpose: Prolonging the drug release can be a suitable approach to overcome the challenges related to topical ophthalmic administration of drugs especially the ones prescribed for chronic ailments. The sustained delivery of the drug would reduce the required frequency of administration which could extremely improve patient compliance and feeling of well-being. This study aimed to develop nanofibrous inserts for sustained ophthalmic delivery of timolol maleate (TIM) for the treatment of glaucoma. Experimental approach: Polycaprolactone-based nanofibers containing TIM were prepared using pure polycaprolactone or a blend of it with cellulose acetate or Eudragit RL100 polymers by the electrospinning method. Following the preparation, polymeric inserts were evaluated for morphological and physicochemical properties. The in vitro drug release was assessed and the in vivo efficacy of a selected insert in decreasing the intraocular pressure (IOP) was also evaluated in the equine eyes. Findings / Results: Prepared nanofibers indicated diameter ranged between 122-174 nm. The formulations showed suitable physicochemical properties and stability for ophthalmic administration. In vitro release study showed prolonged release of drug during more than 3 days. In vivo evaluation revealed that the prepared insert is non-irritant and non-toxic to the equine eyes while having suitable efficacy in decreasing the IOP during 6 days. Conclusions and implication: Prepared TIM inserts indicated a higher efficacy than commercial TIM eye drop in lowering IOP during a prolonged period. Thus, these formulations can be considered suitable for enhancing patient compliance by reducing the frequency of administration in the treatment of glaucoma.

Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas.

Infantile hemangiomas (IH) leave sequelae after involution. Topical application of timolol maleate (TM) is the mainstream treatment for superficial lesions but is limited by its low penetrable properties. We aimed to develop a superior skin permeation drug while maintaining the therapeutic properties of timolol. We predict that this drug will promote the involution of thick and deep IH lesions and avoid sequelae. We chemically modified drug structure to prepare butyryl timolol maleate (BT) prodrug and conducted in vitro and in vivo toxicity evaluations of BT with rat dorsal skin and normal skin cells. Skin permeation and absorption comparisons of TM and BT were conducted using rat and porcine skin models. Conversion efficiency of BT to timolol was also tested on human skin ex vivo. BT did not cause skin irritation on rat dorsal skin and exhibited low cytotoxicity overall. BT exhibited superior skin permeation ability compared with that of TM, whilst maintaining a low systemic absorbance. Further, BT was converted to timolol in human skin in a time-dependent manner. Noticeably, timolol accumulation in the skin from BT was higher than that from TM. Finally, BT demonstrated similar biocompatibility with TM in the IH tumor. BT enhances local delivery of timolol and its skin permeation. Using BT, we could eliminate thicker IH lesions that are prone to leave sequelae, and potentially help young children avoid dermal sequelae, disfigurement, and concomitant therapy.

The Effect of Polymers on Drug Release Kinetics in Nanoemulsion In Situ Gel Formulation.

Glaucoma is an ocular condition characterized by elevated intraocular pressure (IOP). Conventional treatments of glaucoma face poor corneal permeability and bioavailability. To address these issues, a nanoemulsion in situ gel of Timolol maleate was developed in this study by adding the polymer Carbopol 934p. Using Carbopol 934p, a novel ophthalmic pH-induced nanoemulsion in situ gel was formulated. The formulation was liquid at pH 4 and quickly gelled when the pH was raised to 7.4 (Lacrimal pH). The pH-triggered in situ gelling mechanism demonstrated continuous drug release over a 24 h cycle. A total of nine trial formulations were prepared (NEI1-NEI9) and subjected to various physicochemical and in vitro evaluations. According to the in vitro release kinetics, the drug release of Timolol maleate nanoemulsion in situ gel NEI5 followed zero-order kinetics, with a release exponent value of 0.902, indicating that the mechanism of release was non-Fickian diffusion regulated. In vivo results showed that Timolol maleate nanoemulsion in situ gel NEI5 provided a better-sustained release of the drug, compared with the Timolet OD eye drops. The formulation is stable in storage, with no distinguishable change in appearance, physical properties, quality, and percentage drug release. NEI5 also reduces drug administration frequency, which improves patient compliance. Timolol maleate nanoemulsion in situ gel NEI5 achieved the goal of controlled drug delivery with extended-release and cost-effectiveness, lowering the dosage and frequency of drug administration, and thus may improve patient compliance. In conclusion, the stable nanoemulsion in situ gel of Timolol maleate NEI5 decreases intraocular pressure (IOP) over a prolonged period.

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment.

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.

Role of topical beta blockers in regression of infantile capillary hemangioma.

OBJECTIVE: To observe efficacy of Timolol maleate 0.5% by topical and surface application in infantile superficial capillary hemangioma of eyelid. METHODS: This multi-centered clinical case series was carried out at Ophthalmology Department of Bilawal Medical College and Institute of Ophthalmology, LUMHS, Jamshoro from November 2019 to May 2020. We included 14 subjects. All the patients were subjected to detailed clinical examination. Before starting the topical beta blockers, the enrolled subjects had obtained the expert opinion by pediatrician to rule out any preexisting developmental cardio vascular disease. Topical beta blockers 0.5% drops were thus started with, against the ongoing finding of superficial capillary hemangioma of eyelid. RESULTS: There was significant regression in size of infantile hemangioma after treating with topical timolol maleate 0.5%. We included 14 subjects in this study. Mean±SD age of patients was 4.94. Complete regression was seen in 08 subjects at the end of 12 weeks (64%) while 03 were completely cured at 08 weeks (21%) and 01 patient lost follow up with us. No significant ocular and systemic side effects were noted. CONCLUSION: Topical timolol maleate 0.5% can be the first-line treatment modality for superficial capillary hemangiomas due to its better safety and efficacy.

Efficacy Evaluation of 755-nm Long-Pulse Alexandrite Laser Combined with 0.5% Timolol Maleate Eye Drops in the Treatment of Thicker Infantile Hemangioma.

PURPOSE: Assessment of the clinical effectiveness and safety of 755-nm long-pulse alexandrite laser combined with 0.5% timolol maleate eye drops in treating thicker infantile hemangioma (IH). MATERIALS AND METHODS: Retrospective analysis of IH treated with 755-nm long-pulse alexandrite laser and topical timolol in the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to October 2020. Seventy-eight cases were included, with a five-week laser treatment interval. Treatment status was documented during the 35 weeks before each treatment, the effect was assessed at the visual analog scale (VAS), and side effects were recorded. During the 6-month follow-up period, the recurrence and residual skin lesions were monitored. The relationship between IH thickness, treatment duration and VAS was analyzed. RESULTS: Among the 78 children with hemangioma, 4 children were treated with a combination of propranolol, fractional laser and cinnamyl alcohol injection due to poor curative effect. Finally, the lesions were effectively alleviated. At the 5th, 15th, 25th, and 35th weeks of treatment, the average VAS of 74 children were 3.56 ± 1.20, 4.61 ± 1.43, 5.63 ± 1.60, and 6.63 ± 1.72, respectively. We analyzed VAS in different thickness groups with Repeated Measures Analysis of Variance(RMANOVA). The results show that the VAS of the thickness 2-3 mm and 3-5mm groups were higher than the 5-7mm and 7-8mm groups (F group = 440.54, P <0.05, F time = 448.31, P <0.05). During the 6-month follow-up period, none of the 74 children relapsed and the residual skin lesions gradually vanished. CONCLUSION: Combined treatment of IHs with a 755-nm long-pulse alexandrite laser and 0.5% timolol maleate eye drops which has apparent clinical efficacy and safety reduce residual skin lesions and decrease the IH recurrence rate.

Timing and Efficacy of 595-nm Pulsed-Dye Laser Combined with 0.5% Timolol Maleate Solution in the Treatment of Superficial Infantile Hemangiomas.

PURPOSE: Infantile hemangioma (IH) is the most common benign tumor in infancy, and superficial IH is the most common type. IH can reportedly resolve spontaneously, but this is associated with complications, such as scars, atrophy, hypopigmentation, telangiectasia, and skin sagging, in 70% of cases. This study explores the safety and feasibility of therapeutic intervention with the 595-nm pulsed-dye laser (PDL) combined with 0.5% timolol maleate solution in superficial IH and compares the difference in efficacy between the early group and the late group. PATIENTS AND METHODS: This retrospective study examined 167 patients with superficial IH who underwent combination therapy at the Dermatology Clinic of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University between July 2019 and July 2020. The early and late groups were composed of children aged ≤2 and >2 months, respectively. Treatment was administered for 6 months, and patients were followed up for another 6 months. Two independent, double-blinded physicians reviewed photographs of the skin lesions before and after treatment to evaluate efficacy. RESULTS: The early group demonstrated higher treatment efficacy than the late group. The early (n = 45) and late (n = 122) groups had treatment efficacy rates of 95.5% and 86.1%, respectively; the difference was statistically significant (P< 0.05). The early and late groups underwent 3.51 ± 0.50 and 4.73 ± 0.68 months of treatment, respectively; the difference was statistically significant (P< 0.05). Seventeen (44.4%) patients in the early group had immediate adverse reactions but no permanent sequelae, whereas 25 (20.49%) and 13 (10.7%) patients in the late group had immediate and permanent sequelae, respectively. The difference was statistically significant (P<0.05). CONCLUSION: This retrospective study demonstrated that 595-nm PDL combined with 0.5% timolol maleate solution was a safe and effective local treatment for superficial IH. Early treatment required fewer treatments, had better curative effects, and a lower probability of permanent sequelae.

Magnesium Hydroxide Nanoparticles Improve the Ocular Hypotensive Effect of Twice Daily Topical Timolol Maleate in Healthy Dogs.

Timolol maleate (TM), a beta-adrenergic receptor antagonist, is widely used for canine antiglaucoma eye drops; however, its bioavailability is <5%. Our previous study revealed that magnesium hydroxide nanoparticles (nMH) have potency in improving the bioavailability of fixed-combined TM in rodent models. This study aimed to investigate whether the fixed combination with nMH improves the ocular hypotensive effect of TM and affects pupil size (PS), heart rate (HR), and mean arterial pressure (MAP) in clinically healthy dogs. Five clinically healthy dogs were administered topical saline, commercial 0.5% TM, and a 0.01% or 0.1% nMH-0.5% TM fixed combination (0.01% or 0.1% nMH-TM) twice daily in one eye for 7 days with at least a 28-day interval. The changes from baseline were calculated and were statistically analyzed for each drug. IOP was significantly reduced in both 0.01% and 0.1% nMH-TM-treated-dogs compared with saline- and TM-treated dogs. Meanwhile, 0.01% and 0.1% nMH did not exacerbate the side effects of TM. From these results, nMH improved the ocular hypotensive effect of TM without enhancing side effects. Topical nMH-TM is potentially more effective for canine ocular hypotensive eye drops than TM.

Quality of timolol eye drops marketed in Kinshasa, Democratic Republic of the Congo.

OBJECTIVE: To assess the quality of timolol eye drops sold in Kinshasa, Democratic Republic of Congo (DRC). METHODS: Seven samples of timolol maleate 0.5% were purchased over the counter in seven randomly selected public pharmacies in 3 neighborhoods in Kinshasa. They were submitted to a quality assessment that included visual inspection, spectrophotometry, high performance liquid chromatography (HPLC), and bacteriologic assessment. RESULTS: The samples came from France (n=2), India (n=2) and DRC (n=3). Overall, 3 (2 from India and 1 from the DRC) of the 7 samples, or 3 out of the 5 from developing countries, showed various abnormalities consistent with substandard drugs. One sample (India) demonstrated an incorrect pH, while 3 (2 from India and one from the DRC) had lower than stated volumes as well as lower than required concentrations of the active pharmaceutical ingredient. In addition, one sample from the DRC was bacteriologically contaminated. CONCLUSION: These results suggest that some timolol maleate eye drops from Congolese and Indian manufacturers sold in Kinshasa are of substandard quality. This may reflect deficiencies in the manufacturers and local authorities charged with regulation of the quality control and sale of pharmaceuticals. Passing a visual inspection does not necessarily indicate that a drug is not substandard. Analytical chemistry testing and bacteriologic analysis are required to determine with certainty the quality of the drug.