Background: Acyclovir, BCS Class III drug is commercially available as 3% w/w eye
ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because
of improved permeation characteristics. Further, the development of in situ ophthalmic gels
can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining
Objective: The purpose of this study was the development and evaluation of nanoemulsions based
in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems.
Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method
using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant,
respectively selected on the basis of Acyclovir solubility in the oil phase and emulsification
ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using
gellan gum and Methocel K4M.
Results: The developed gels showed a sustained effect in vitro release studies and improved goat
corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies
concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the
absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological
studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal
stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel
showed increased corneal deposition and permeation in isolated rat eyes.
Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced
frequency of application compared to the marketed ointment in animal studies.