Optimization of experimental parameters for the production of LMWH-loaded polymeric microspheres

Figures & data

Table 1 Factors and levels in the Box-Behnken design

	Levels
Independent variables	Low	Middle	High
X1 = Polymer concentration (%)	1	5	9
X2 = Inlet temperature (°C)	80	90	100
X3 = Feed flow rate (%)	15	20	25
	Constraints
Dependent variables	Low	High	Goal
Y1 = Production yield (%)	20	100	maximize
Y2 = Mean particle size (μm)	1	30	minimize

Table 2 Box-Behnken experimental design grid and responses pertaining to microparticle production

Run no.	Polymer concentration (%)	Inlet tem- perature	Feed flow rate (%)	Production yield	Mean particle size
		(°C)		(%)	(μm)
1	1	100	20	51.89	26.13
2	1	80	20	0	N/A
3	9	100	20	59.26	42.92
4	5	80	15	23.45	19.62
5	9	90	15	53.37	32.66
6	5	90	20	47.45	25.79
7	1	90	25	0	N/A
8	9	80	20	23.33	22.36
9	5	100	25	56.55	24.98
10	5	80	25	20	40.18
11	9	90	25	18.84	32.78
12	1	90	15	25.33	36.27
13	5	100	15	47.45	25.09
14	5	90	20	28.36	30.54
15	5	90	20	25.82	27.02

Table 3 Fractal dimension and residual moisture content for microparticles prepared by spray drying

Formulation no.	Fractal dimension (n = 3) (Df)	Moisture content (n = 3) (%)
1	1.74 ± 0.06	4.80 ± 0.05
2	N/A	N/A
3	1.4 ± 0.06	4.13 ± 0.01
4	1.72 ± 0.03	4.04 ± 0.02
5	1.55 ± 0.05	3.66 ± 0.03
6	1.67 ± 0.09	5.24 ± 0.10
7	N/A	N/A
8	1.54 ± 0.10	2.80 ± 0.07
9	1.59 ± 0.13	3.45 ± 0.01
10	1.76 ± 0.06	3.53 ± 0.10
11	1.59 ± 0.05	4.64 ± 0.12
12	1.87 ± 0.005	4.53 ± 0.10
13	1.69 ± 0.10	5.08 ± 0.05
14	1.63 ± 0.08	5.04 ± 0.01
15	1.58 ± 0.16	5.11 ± 0.08

Figure 1 Scanning electron micrographs of spray-dried microparticles and native heparin. (Magnification 200X. scale corresponds to 200 μm) Note: no particles obtained for run no.’s 2 and 7.

Figure 2 Standardized Pareto chart for main effects of experimental parameters on the responses.

Figure 3 Response surface wire frame plot with contours below for (a) percent yield and (b) particle size as a function of the spray drying operating parameters.