Biomedical Engineering Reference
In-Depth Information
have affinity for CO
2
. In pharmaceutical processing scCO
2
offers a particular
advantage in that the polymer plasticization processing can be carried out at low
temperatures [
52
] which is important for thermally sensitive drug or biomaterials
(e.g. enzyme) formulations, where the incipient may degrade when exposed to high
temperatures [
53
].
The development of sustained drug delivery based on the use of supercritical
fluid assisted mixing of drug particles and biological materials in degradable/non-
degradable polymers is an innovative application of the methodology and one
of the main reasons for polymer processing in pharmaceutical field. This kind
of pharmaceutical preparations permit to obtain fast release for drugs with low
water solubilities, prolonged-delayed release for drugs with high water solubilities,
protection of the active principle, minimization of haematic concentration peaks
avoiding side effects and better patient compliance [
54
]. The resulting products can
be used for tissue engineering applications such as scaffolds and controlled drug
delivery devices using both biodegradable and non-biodegradable polymers. The
above mentioned high diffusivity and low surface tension of dense CO
2
enables
it to easily penetrate into the polymeric matrix, dispersing solutes throughout
the polymer. Furthermore, this diffusion enhancement can be controlled (“tuned”)
just by changing the operational pressure and temperature. Upon depressurization
the CO
2
-soluble compounds become entrapped in the polymer substrate, and can
also cause the polymer substrate to foam. When returning back to atmospheric
temperature and pressure, dense CO
2
will return to its gaseous state without leaving
any residual solvent, originating a highly pure final product [
53
,
55
]. Therefore,
impregnation using scCO
2
results from the equilibrium between CO
2
swelling and
plasticizing capacity and CO
2
solubility for the additive(s) to be loaded, assuring
the appropriate plasticization of the polymeric substrate as well as the appropriate
solvent power for the additive(s). This will strongly favor the additive partition
into the polymeric phase over the supercritical phase, yielding higher loadings
and a more uniform distribution of the additives in the whole polymeric substrate
[
56
-
58
].
Although CO
2
is the most frequently employed SCF, it also presents several
limitations mainly due to its inability to dissolve high molecular weight compounds
and to its non-polarity and lack of several specific solvent-solute and solvent-
polymer interactions that would lead to high polymeric drug loading. A frequent
strategy to increase drug solubility in scCO
2
is the addition of small amounts of
specific co-solvents (like ethanol or water) which can change its solvent power,
sometimes up to several hundred percent in terms of solubility enhancement [
59
,
60
]. The efficacy of a dense CO
2
process to create a controlled drug delivery
system is dependent on pressure, glass transition temperature (Tg) of the polymer
and interactions between the polymer, bioactive substance and dense CO
2
.The
dispersion of the drug within the polymer matrix is dependent on the drug CO
2
solubility as well as on the drug affinity for the polymer. Two different impregnation
mechanisms may occur. The first one is explained by the interaction of the drug
molecules with the polymer active sites: the drug molecules leave the supercritical
phase and reach the polymeric active sites, while the concentration of the drug in
