Levobunolol 0.5% eye drops 0.4ml unit dose preservative free

Background/aimsTo assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP).MethodsA systematic literature review adapted from the Li et al (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated.ResultsA total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%.ConclusionLBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.

Abstract licence: CC BY-NC

Abstract Context A detailed molecular-level rationale for the enantioseparation of the β-blocker levobunolol (BUN) by substituted β-cyclodextrins (β-CDs) is presented through high-level computational modeling. The calculations consistently reveal that the therapeutically active (+)-[S]-BUN enantiomer forms more stable inclusion complexes than the (−)-[R]-enantiomer with both carboxymethyl-β-CD (CM-β-CD) and sulfated-β-CD (SF-β-CD) selectors. Non-covalent interaction (NCI) reveals that the superior stability of the S-enantiomer arises from a more continuous dispersive interaction envelope and a more compact network of electrostatic and hydrogen bonds. For the most effective selector, SF-β-CD, the complexation Gibbs free energy (ΔG) in an aqueous medium is −29.5 kcal/mol for (+)-[S]-BUN versus −17.1 kcal/mol for (−)-[R]-BUN. This results in a large free energy difference (ΔΔG) of 12.4 kcal/mol, indicating exceptional enantioselectivity. The NCI isosurfaces also confirm that the S-isomer achieves optimal stereoelectronic complementarity with the host’s sulfate and hydroxyl groups, showing lower steric penalties than the R-isomer. These findings provide a robust prediction of a longer electrophoretic migration time for the (+)-[S]-enantiomer and validate SF-β-CD as a highly efficient chiral selector for BUN, underscoring the power of in silico methods to elucidate complex chiral recognition mechanisms. Methods Semiempirical geometry, frequency, non-covalent, 2nd version, eXtended Tight Binding (GFN2-xTB) and Density Functional Theory (DFT) (ωB97X-D3/6-31G(d,p) and ωB97X-D3/6–311 + G(d,p)) methods were employed in both gas and aqueous phases. NCI analysis was also performed. All DFT and semiempirical calculations were carried out using the ORCA 5.0 software package. The NCI analysis was carried out using the Multiwfn program.

Abstract licence: CC BY 4.0

Majorly, the reason for the permanent loss of vision is glaucoma. But the currently available common treatment methodologies such as eye drops have various disadvantages like patient incompliance due to repeated administration and poor (1–5%) bioavailability leading to poor efficiency. The objective of this research was to formulate Eudragit-based nanoparticles of levobunolol incorporated into a contact lens to obtain sustained ocular delivery of levobunolol at the therapeutics level. Eudragit nanoparticles of levobunolol were formulated by nanoprecipitation methodology utilizing different ratios of Eudragit S100 and polyvinyl alcohol. The prepared nanoparticles were evaluated and optimized by efficiency of entrapment, particle size, morphology of surface and zeta potential. The optimized nanoparticles were then entrapped into the matrix of the contact lens by the soaking method which were then characterized and compared for optical clarity study, equilibrium swelling study, shelf life and in vitro drug release in simulated tear fluid followed by ex vivo transcorneal permeation study. Formulation F3 was obtained as optimized nanoparticle formulation with 102.61 nm ± 3.92 of particle size, − 22.2 mV ± 2.76 of zeta potential and 86.995% ± 1.902 of efficiency of entrapment. The equilibrium swelling index and transmittance of nanoparticle incorporated into contact lenses showed better results when compared to drug solution-loaded lenses. In vitro release indicated more sustained drug profiles (84.33% ± 0.34 of drug release over a period of 12 days) as compared to drug solution-loaded lenses (89.282% ± 0.900 of drug release over a period of 3 days). Ex vivo transcorneal permeation studies showed more permeation (6.75% ± 0.170) through contact lenses as compared to marketed eye drops (3.03% ± 0.088). This research demonstrates the remarkable results of drug-laden contact lenses to serve as a great medium for the continued delivery of ocular drugs without affecting the physical and optical characteristics of the lens content.

Abstract licence: CC BY 4.0