The role of hyaluronan as a drug carrier to enhance the bioavailability of extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a model case.

The aim of this work was to obtain information concerning the properties of ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the factors that determine the onset, intensity and duration of the pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and presented a counterionic condensation higher than 75%. For comparison a similar complex obtained with hyaluronic acid (HyH) was also prepared. Although the viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro release of TM from both complexes showed a similar extended drug release profile (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM complex exhibited attractive bioavailability properties in the aqueous humor (AUC and Cmax significantly higher and later Tmax) compared to commercial TM eye-drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h) and a more intense hypotensive activity was observed after instillation of a drop of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer pre-corneal residence times (400%) observed with HyNa-TM complex. No significant changes in rabbit transcorneal permeation were detected upon complexation. These results demonstrate that the ability of HyNa to modulate TM release, together with its mucoadhesiveness related to the viscosity, affected both the pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a potentially useful carrier for ocular drug delivery, which could improve the TM efficacy and reduce the frequency of administration to improve patient compliance.

Does the type of treatment have an influence on utility values in a glaucoma population?

PURPOSE: To assess the impact of glaucoma therapy on utility values in a glaucoma population. METHODS: A cross-sectional study of consecutive glaucoma patients was conducted. Utility values were obtained using the time trade-off method. Visual function variables (visual acuity and mean deviation in the better eye) and sociodemographic and clinical characteristics (age, sex, race, educational level, type of glaucoma, current and past glaucoma treatments, and comorbidities) were also obtained for statistical analysis. We divided the patients into three groups: medical treatment (group 1), surgical treatment (group 2), and mixed surgical and medical treatment (group 3). RESULTS: Mean age of the study population (n=225) was 65.7 years. After controlling for glaucoma stage (early, moderate, and advanced), the difference among the groups in mean utility values was not statistically significant. Number of medications per patient, type of medication, or type of surgical technique did not have an impact on the utility values. CONCLUSION: Our findings suggest that the type of therapy did not affect the utility values in a glaucoma population.