Natural and synthetic oil phase transition microemulsions for ocular delivery of tropicamide: efficacy and safety

The objective of this work was to investigate the efficacy and safety of natural oils (castor oil and olive oil) based phase transition microemulsion systems for ocular delivery with reference to ethyl oleate systems. Tropicamide was used as model drug and was incorporated in the formulation at a concentration of 0.5% w/w. The phase transition systems comprised the oil, surfactant and water with the phase behavior depending on the concentration of water. The tested systems included microemulsion (ME), liquid crystalline system (LC) and coarse emulsion (EM). The efficacy of these systems was evaluated by monitoring the mydriatic response in comparison to drug solution containing polyvinylpyrrolidone (PVP). Ocular irritation was monitored by visual inspection and tear flow estimation. Drug release depended on the formulation type and viscosity. Thus LC systems produced the slowest release rates followed by the ME with the EM producing the largest release rate. The mydriatic response versus time plots showed biphasic effect with two maxima (MRmax) which verified the systemic absorption of the drug. Both ethyl oleate and olive oil based systems were more effective than the control with respect to the area under the mydriatic response profile. However, castor oil based systems were comparable to the control. With respect to ocular irritation castor oil based system were the least irritant followed by olive oil systems with ethyl oleate systems being the most irritant. The study thus introduced olive oil based phase transition systems for ocular drug delivery with lower irritation compared to the synthetic oil systems.