Pharmaceutical Manufacturing Handbook: Production and

1352 OIL-IN-WATER NANOSIZED EMULSIONS
CsA concentration, ng/g
2800
2400
2000
1600
1200
800
400
0
Cornea positive emulsion
Cornea negative emulsion
Conjunctiva positive emulsion
Conjunctiva negative emulsion
15 30 60 120 180 480
Time (min)
FIGURE 4 Infl uence of emulsion surface charges cyclosporin A (CsA) concentrations in
ocular surface tissues (cornea and conjunctiva) following one single - dose (50 - μ L) instillation
of positively (cationic) and negatively (anionic) charged CsA - loaded nanosized emulsions
into albino rabbit eye.
This long residence time may help reduce evaporation of the limited volume of
natural tears present in patients with dry eye. This was probably due to the adhesion
of the positively charged oil droplets to the negatively charged corneal surface
moieties as a result of electrostatic attraction. This hypothesis was supported by data
from an ex vivo study which showed that cationic emulsion exhibited better wettability
properties on albino rabbit eye cornea than either saline or anionic emulsion
[108] . Associated with Poloxamer and phospholipids, a cationic primary amine,
stearylamine, has been used to obtain the above - described third - generation cationic
emulsions. Additionally, a cationic emulsion based on an association of Poloxamer
188 and chitosan was prepared and also showed interesting physicochemical properties
on stability and charge effects [97, 98] . Moreover, the stability and ocular tolerance
following topical instillation into the eye of these cationic emulsion vehicles
were investigated [98, 114] . The overall studies hence stress the effectiveness of
nanosized cationic emulsion, which promotes ocular drug absorption via internalization
possibly through an endocytic process [112] .
7.4.5.3 Nasal Route
The nasal route is still receiving great attention due to a number of advantages over
parenteral and oral administration [180] , particularly when fi rst - pass metabolism
makes the drug ineffective. The approach of an o/w emulsion formulation of the
drug may increase absorption by solubilizing the drug in the inner phase of
the emulsion and prolonging contact time between emulsion droplets and nasal
mucosa.
One of the fi rst examples for systemic delivery of peptides concerned a lipid -
soluble rennin inhibitor [181] . The peptide was solubilized in the oil phase of an o/w
emulsion containing membrane adjuvants such as oleic acid and mono - and diglyc-