Polymeric ocular nanosuspension for controlled release of acyclovir: in vitro release and ocular distribution

The aim of this study is to formulate a novel ophthalmic nanosuspension (ONS), an alternative carrier system to traditional colloidal carriers for controlled release (CR) of acyclovir (ACV). In the present study, ONS is employed to avoid some of major disadvantages of colloidal carriers systems such as instability in cul de sac and short half life by increasing efficiency of drug encapsulation as well as by CR. A quassi-emulsion solvent evaporation method was used to prepare ACV loaded Eudragit RS 100 ONS with the aim of improved ocular bioavailability and distribution. Five different formulations were prepared and evaluated for pH of ONS, particle size, entrapment efficiency, differential scanning calorimetry (DSC), in vitro release profile, in vivo release studies and stability studies. An average size range of 100 to 300 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Cumulative percent drug released for all formulations after 24 h was between 79.28 to 95% indicating effective CR property of ONS. The release profile revealed from best formulation followed Non-Fickian diffusion mechanism. In vivo studies showed that ACV concentration in aqueous humor at 8 h was 82.83, 77.49 and 34.15 mg/ml. Stability studies showed a maximum drug content and almost similar in vitro release compared to the initial data found for the sample stored at 4°C. Overall, the study also revealed that ONS was capable of releasing the drug for a prolonged period of time and increased bioavailability.