03-09-2012, 12:15 PM
FORMULATION AND CHARACTERIZATION OF TOPICAL LIPOSOME GEL BEARING LIDOCAINE HCl
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ABSTRACT
Liposome gels, bearing lidocaine hydrochloride, intended for topical application have been prepared and
evaluated.
Liposomes composed of Soya lecithin and cholesterol, with lidocaine hydrochloride entrapped in the inner water
compartment, were prepared by the simple mechanical method vortexing the phospholipid dispersion in water.
Topical liposome gels were prepared by incorporation of liposomes into a structured vehicle (1.5, 1.75 and 2 % Carbopol
gel base). Also, corresponding hydrogels were prepared and drug release properties were investigated.
High percentage of encapsulated drug into liposomes has been obtained (over 72 %). Liposome gels provided a
prolonged drug release rate. The concentration of the gelling agent affected the release rate slightly. Also, embedding
liposomes into a structured vehicle of Carbopol resulted in significantly slower drug release than hydrogels. Exponential
dependence of the amount of drug released on time was evidenced; the diffusion exponents were superior to
0.5, indicating anomalous Fickian diffusion, generally due to the swelling of the system in the solvent before the release
took place. The mathematical processing of drug release data showed that after the 3rd hour liposomes acted as
reservoir systems for continuous delivery of encapsulated drug.
Proposed formulations provided a stable percentage of encapsulated drug and drug release within an examination
period of 3 weeks.
INTRODUCTION
The search continues for safe and effective
topical anesthetic preparation that can ease the
pain during minor dermal procedures, such as intravenous
cannulation, vaccination, curcumcision,
venipunction, punch biopsy and other small surgical
inclusions [1].
Lidocaine is safe and the most widely used
local anesthetic agent, but due to the low permeability
through the stratum coneum (SC) and relatively
high drug concentration required in local
tissues for effective anesthesia, the use of lidocaine
for anesthesia of intact skin has to date been
quite disappointing. Topical lidocaine formulations
may be prepared as conventional pharmaceutical
creams and gels, but those products can not
effective deliver lidocaine through intact skin due
to the barrier function of the SC. It is composed of
dead, flattened calls, filled with keratin, in the
form of a regular array of protein rich cells embedded
in an intercellular multilamellar lipid domain
running parallel to the skin [2, 3]. Several
experiments have shown that lipoidal domains, the
integral components of the transport barrier must
be breached if the drug is to be delivered at an appropriate
rate. Several enhancement techniques
have been developed to overcome the impervious
nature of the SC, i.e. ionophoresis, chemical enhancement,
application of supersaturated drug systems,
prodrugs and liposome vesicles [4–6].
EXPERIMENTAL
Materials
Hydrogenated Soya lecithin (phospholipid
content above 70 %, and PC content ~35 %) was
supplied from Soya protein (Serbia and Montenegro)
and cholesterol from Galenika (Serbia and Montenegro).
Lidocaine hydrochloride (Lidocaine HCl) was a
generous gift from Siegfried (Switzerland). Carbopol
940 (Alpha Pharma, Belgium) was used as a gelling
agent. All other materials and solvents were of an
analytical grade.
Preparation of liposome gel formulations
Multilamellar liposomes (MLV) containing
the local anaesthetic agent Lidocaine HCl (5.4
w/w) were prepared by the simple mixing method,
vortexing the lipid dispersion in water [13]. In brief:
the lipid phase containing lecithin/cholesterol in
mass ratio 9:1 (total lipids content 27 % w/w) was
hydrated for 2 h at room temperature with occasional
vigorous mixing (200–300 min–1) with an
aqueous phase (purified water bearing total drug
quantity), so the final lipid/aqueous phase mass
ratio was 1:2.7 and drug/lipid mass ratio 1:5. Afterwards,
the prepared sample was allowed to
stand for 24 h at 4 oC [14].
RESULTS AND DISCUSSION
Characterization of liposome gels
The prepared topical liposome formulations
were clear, homogenized gels with light-yellowish
colour. To be closer to the application of liposomes
in humans, an appropriate viscosity of liposome
preparation is required. This can be achieved
by their incorporation in a vehicle suitable for
topical application. One of the limitations of conventional
topical dosage forms on the skin is relatively
short residence time of the drug at the site of
application. Because a controlled release and prolonged
retention on the skin is often required for
the desired therapeutic effect, research efforts have
been directed to using hydrophilic polymers with
bioadhesive characteristics to improve drug delivery.
It has already been proven that liposomes are
fairly compatible with polymers derived from
crosslinking poly(acrylic acid) polymers [23].
CONCLUSION
This study suggests that liposome gel formulations
containing Lidocaine HCl could perform
therapeutically better effects than the conventional
formulations, as prolonged and controlled
release topical dosage forms, which may
lead to improved efficiency and better patient
compliance.