advertisement
Abstract #73072 Published in IGR 18-4
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
Battistini FD; Tártara LI; Boiero C; Guzmán ML; Luciani-Giaccobbe LC; Palma SD; Allemandi DA; Manzo RH; Olivera MEEuropean Journal of Pharmaceutical Sciences 2017; 105: 188-194
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.
Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000 Córdoba, Argentina.
Full articleClassification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
