However, the mixing protocol for polycation and polyanion solutions is not extensively described in the reports on PEL complexation. Often, PEL solutions are
mixed (for the order of addition see Sect. 2.2.3) using magnetic stirrers at a fixed
velocity. Only a few systematic studies can be found describing this important
aspect.
Recently, Wa ˚gberg and coworkers reported the influence of mixing procedure
on the complexation of poly(allylamine) (PAH) and poly(acrylic acid) (PAC) by
comparing jet mixing [43] with the frequently used mode termed “colloid titration”
[44], which should not be confused with the analytical technique mentioned above.
They obtained small PECs for both low molecular weight PELs at short mixing
times, whereas for high molecular weight PELs PEC size first decreased with
decreasing mixing time until a minimum and then increased again. This behavior
was explained by diffusion-controlled formation of “precomplexes” occurring
sufficiently quickly so that stable complexes were formed. However, for larger
PELs non-equilibrium precomplexes prone to aggregation were formed. Comparing the two mixing procedures, jet mixing gave smaller PECs, allowing mixing time
to control PEC size, whereas PEL titration gave larger PECs. Furthermore, higher
PEL concentration gave larger jet-mixed PECs.
Qualitatively similar results were obtained by Saether et al., who reported the
influence of mixing speed on the particle size of chitosan/alginate (CHT/ALG) PEC
particles [45] using an Ultraturrax procedure. With increasing mixing speed,
smaller CHT/ALG particles were obtained.
Schatz and coworkers reported another mixing procedure dependence, comparing ordinary dropwise mixing with one-shot mixing [46] for the chitosan/dextran
sulfate (CHT/DS) system. They found that the rapid one-shot mixing process gave
PEC colloids with higher stability and lower diameters compared with the dropwise
mixing process.
2.2.3 Order of Addition
A very sensitive experimental parameter was found by several authors to be the
order of PEL addition when the PEL solutions are mixed slowly with one another
[47, 48]. In principle, nonstoichiometric mixing ratios n
À
/n
+
< 1 or n
À /n
+
> 1 can
be experimentally achieved by dosing the minority component into the majority
component or vice versa. For example, a PEC-0.66 can be prepared by dosing the
minority PA solution into the majority PC solution (“minor-to-major”) or by dosing
the majority PC into the minority PA solution (“major-to-minor”). For the PEC
system of PEI/PAC we found smaller particle sizes for minor-to-major dosing and
larger ones for major-to-minor (see Fig. 7) [48]. Obviously, there is a dramatic
difference between minor-to-major dosing, which is related to the interval
n
À /n
+
¼ 0.1–0.7 for addition of PEI to PAC (1. PEI 2. PAC) or n
À /n
+
¼ 1.0–1.6
for addition of PAC to PEI (1. PAC 2. PEI), and major-to-minor dosing, which is
related to the interval n
À
/n
+
¼ 0.9–1.6 for 1. PEI 2. PAC or n
À /n
+
¼ 0.1–0.8 for
1. PAC 2. PEI. For the former case (minor-to-major), we suggest a more
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
205
mixed (for the order of addition see Sect. 2.2.3) using magnetic stirrers at a fixed
velocity. Only a few systematic studies can be found describing this important
aspect.
Recently, Wa ˚gberg and coworkers reported the influence of mixing procedure
on the complexation of poly(allylamine) (PAH) and poly(acrylic acid) (PAC) by
comparing jet mixing [43] with the frequently used mode termed “colloid titration”
[44], which should not be confused with the analytical technique mentioned above.
They obtained small PECs for both low molecular weight PELs at short mixing
times, whereas for high molecular weight PELs PEC size first decreased with
decreasing mixing time until a minimum and then increased again. This behavior
was explained by diffusion-controlled formation of “precomplexes” occurring
sufficiently quickly so that stable complexes were formed. However, for larger
PELs non-equilibrium precomplexes prone to aggregation were formed. Comparing the two mixing procedures, jet mixing gave smaller PECs, allowing mixing time
to control PEC size, whereas PEL titration gave larger PECs. Furthermore, higher
PEL concentration gave larger jet-mixed PECs.
Qualitatively similar results were obtained by Saether et al., who reported the
influence of mixing speed on the particle size of chitosan/alginate (CHT/ALG) PEC
particles [45] using an Ultraturrax procedure. With increasing mixing speed,
smaller CHT/ALG particles were obtained.
Schatz and coworkers reported another mixing procedure dependence, comparing ordinary dropwise mixing with one-shot mixing [46] for the chitosan/dextran
sulfate (CHT/DS) system. They found that the rapid one-shot mixing process gave
PEC colloids with higher stability and lower diameters compared with the dropwise
mixing process.
2.2.3 Order of Addition
A very sensitive experimental parameter was found by several authors to be the
order of PEL addition when the PEL solutions are mixed slowly with one another
[47, 48]. In principle, nonstoichiometric mixing ratios n
À
/n
+
< 1 or n
À /n
+
> 1 can
be experimentally achieved by dosing the minority component into the majority
component or vice versa. For example, a PEC-0.66 can be prepared by dosing the
minority PA solution into the majority PC solution (“minor-to-major”) or by dosing
the majority PC into the minority PA solution (“major-to-minor”). For the PEC
system of PEI/PAC we found smaller particle sizes for minor-to-major dosing and
larger ones for major-to-minor (see Fig. 7) [48]. Obviously, there is a dramatic
difference between minor-to-major dosing, which is related to the interval
n
À /n
+
¼ 0.1–0.7 for addition of PEI to PAC (1. PEI 2. PAC) or n
À /n
+
¼ 1.0–1.6
for addition of PAC to PEI (1. PAC 2. PEI), and major-to-minor dosing, which is
related to the interval n
À
/n
+
¼ 0.9–1.6 for 1. PEI 2. PAC or n
À /n
+
¼ 0.1–0.8 for
1. PAC 2. PEI. For the former case (minor-to-major), we suggest a more
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
205