Pharmaceutical Manufacturing Handbook: Production and

DESIGN AND FABRICATION OF CONTROLLED-RELEASE DOSAGE FORMS 365
and poly(alkylcyanoacrylate), which are most commonly employed [65] . Similarly,
a broad range of oils is suitable for the preparation of nanocapsules/nanospheres,
including vegetable or mineral oils and pure compounds such as ethyl oleate and
benzyl benzoate. The criteria for the selection of these compounds are the nontoxicity
and the low solubility of the oil in the polymers and vice versa.
Both hydrophilic and lipophilic surfactants can be used to stabilize the polymeric
nanoparticles. Generally the lipophilic surfactant is a natural lecithin of relatively
low phosphotidylcholine content, whereas the hydrophilic one is synthetic: anionic
(lauryl sulfate), cationic (quaternary ammonium), or more commonly nonionic
[poly(oxyethylene) - poly(propylene)glycol]. Nanoparticles can be prepared in the
absence of surfactants, but there are lots more chances to get aggregated during
storage.
2. Nanoparticles Obtained by Multiple Emulsion/Solvent Evaporation Method
The multiple emulsion/solvent evaporation method was initially developed for the
preparation of microcapsules. This method consists in fi rst dissolving the drug in an
aqueous solution with or without a surfactant and the polymer in a volatile organic
solvent that is not miscible to water. Polymers used for the formation of such types
of particles have been mainly poly(lactide - co - glycolide) and poly( ε - caprolactone)
[66, 67] . The inner water phase is then poured into the organic phase. This mixture
is generally emulsifi ed forming the fi rst inner emulsion or the primary W/O emulsion,
which is then mixed vigorously into an aqueous phase (outer water phase) that
contains an emulsifi er forming the water - in - oil - in - water (W/O/W) multiple emulsion.
The resulting multiple nanoemulsion is continuously stirred and the solvent is
allowed to evaporate, inducing precipitation of polymer and, thereby, the formation
of solid drug loaded nanoparticles.
5.1.6.3 Liposomes
Liposomes were discovered in the mid - 1960s [68] and were originally studied as cell
membrane models. They have since gained recognition in the fi eld of drug delivery.
Liposomes are formed by the self - assembly of phospholipid molecules in an aqueous
environment. The amphophilic phospholipid molecules form a closed bilayer sphere
in an attempt to shield their hydrophobic groups from the aqueous environment
while still maintaining contact with aqueous phase via the hydrophilic head group.
The resulting closed sphere may encapsulate aqueous soluble drugs within the
central aqueous compartment or lipid - soluble drugs within the bilayer membrane.
Alternatively, lipid - soluble drugs may be complexed with other polymers (e.g.,
cyclodextrin) and subsequently encapsulated within the liposome aqueous compartment.
The encapsulation within/association of drugs with liposomes alters the drug
pharmacokinetics.
Attractive Biological Properties of Liposomes [69]
• Liposomes are biocompatible.
• Liposomes can entrap hydrophilic bioactive compounds in their internal compartment
and hydrophobic into the membrane.
• Liposome - incorporated bioactives are protected from the inactivating effect of
external conditions yet do not cause undesirable side reactions.