Pharmaceutical Manufacturing Handbook: Production and

748 OCULAR DRUG DELIVERY
tigated in this regard were poly(acrylic acid) (PAA), hyaluronic acid (HA), chitosan,
and poloxamer [36, 43, 121 – 122, 214] .
Durrani and co - workers [122] reported on the infl uence of a carbopol coating on
the corneal retention of pilocarpine - loaded liposomes, and demonstrated a biphasic
response with an initial low intensity followed by a sustained reaction.
Bochot et al. [124, 125] developed a novel delivery system for oligonucleotides
by incorporating them into liposomes and then dispersing them into a thermosensitive
gel composed of poloxamer 407. They compared the in vitro release of the
model oligonucleotides pdT16 from simple poloxamer gels (20 and 27% poloxamer)
with the ones where pdT16 was encapsulated into liposomes and then dispersed
within the gels. They found that the release of the oligonucleotides from the gels
was controlled by the poloxamer dissolution, whereas the dispersion of liposomes
within 27% poloxamer gel was shown to slow down the diffusion of pdT16 out of
the gel.
Niosomes In order to circumvent some of the limitations encountered with
liposomes, such as their chemical instability, the cost and purity of the natural
phospholipids, and oxidative degradation of the phospholipids, niosomes have been
developed. Niosomes are nonionic surfactant vesicles which exhibit the same bilayered
structures as liposomes. Their advantages over liposomes include improved
chemical stability and low production costs. Moreover, niosomes are biocompatible,
biodegradable, and nonimmunogenic [215] . They were also shown to increase the
ocular bioavailability of hydrophilic drugs signifi cantly more than liposomes. This is
due to the fact that the surfactants in the niosomes act as penetrations enhancers
and remove the mucous layer from the ocular surface [209] .
A modifi ed version of niosomes are the so - called discomes, which vary from the
conventional niosomes in size and shape. The larger size of the vesicles (12 – 60 μ m)
prevents their drainage into the nasolacrimal drainage system. Furthermore, their
disclike shape provides them with a better fi t in the cul - de - sac of the eye [26] .
Vyas et al. [216] demonstrated that discomes entrapped higher amounts of timolol
maleate than niosomes and that both niosomes and discomes signifi cantly increased
the bioavailability of timolol maleate when compared to a conventional timolol
maleate solution.
Microemulsions Microemulsions (MEs) are colloidal dispersions composed of an
oil phase, an aqueous phase, and one or more surfactants. They are optically isotropic
and thermodynamically stable and appear as transparent liquids as the droplet
size of the dispersed phase is less than 150 nm. One of their main advantages is their
ability to increase the solubilization of lipophilic and hydrophilic drugs accompanied
by a decrease in systemic absorption [217] . Moreover, MEs are transparent
systems thus enable monitoring of phase separation and/or precipitation. In addition,
MEs possess low surface tension and therefore exhibit good wetting and
spreading properties.
While the presence of surfactants is advantageous due to an increase in cellular
membrane permeability, which facilitates drug absorption and bioavailability [218] ,
caution needs to be taken in relation to the amount of surfactant incorporated, as
high concentrations can lead to ocular toxicity. In general, nonionic surfactants are
preferred over ionic ones, which are generally too toxic to be used in ophthalmic