Effects of formulation and operating variables on Zanamivir dry powder inhalation characteristics and aerosolization performance

Figures & data

Table 1. Formulation design.

Batch	Composition	Concentration of spray-drying solution (g/100 mL)
1	Zanamivir	1
2	Zanamivir/mannitol	1/4
3	Zanamivir/mannitol/leucine	1/3/1
4	Zanamivir/mannitol/leucine	1/2/2
5	Zanamivir/mannitol/leucine	1/1/3

Figure 1. The zanamivir spray-drying powders yield of the different formulation.

Figure 2. Scanning electron micrographs showing the particle morphology of zanamivir spray-drying powders at various formulations. (a) The powders prepared with zanamivir, Batch 1; (b) the powders prepared with zanamivir/mannitol (1/4), Batch 2; (c) the powders prepared with zanamivir/mannitol/leucine (1/3/1), Batch 3; (d) the powders prepared with zanamivir/mannitol/leucine (1/2/2), Batch 4; (e) the powders prepared with zanamivir/mannitol/leucine (1/1/3), Batch 5.

Table 2. Characteristics of zanamivir spray-drying powders (n = 3).

Batch	ρ (g.cm^−3)	α	Dg (μm)	FPF (%)
1	0.62 ± 0.03	59° ± 1	9.28 ± 0.09	5.43 ± 1.7
2	0.47 ± 0.02	43° ± 1	5.88 ± 0.15	16.33 ± 1.2
3	0.42 ± 0.01	39° ± 2	4.48 ± 0.12	25.62 ± 1.3
4	0.38 ± 0.02	33° ± 2	4.07 ± 0.07	30.62 ± 1.5
5	0.32 ± 0.01	36° ± 1	3.11 ± 0.13	41.40 ± 1.1
Relenza®	0.50 ± 0.01	46° ± 1	3.67 ± 0.17	34.21 ± 0.9

Figure 3. Moisture adsorption profile of zanamivir spray-drying powders at 45–85% relative humidity at 25 °C.

Table 3. Spray-drying variables and characteristics (Batch 5, zanamivir/mannitol/leucine, 1/1/3, n = 3).

No.	Feed flow rate (mL min^−1)	Atomizing pressure (kPa)	Air flow rate (m^3 min^−1)	Inlet temperature (°C)	Yield (%)	ρ (g cm^−3)	α	Dg (μm)	FPF (%)
1	1.5	18	0.6	130	48	0.38 ± 0.01	33° ± 2	3.18 ± 0.20	35.56 ± 2.2
2	2	18	0.6	130	41	0.32 ± 0.01	36° ± 1	3.11 ± 0.13	41.40 ± 1.1
3	2.5	18	0.6	130	23	0.29 ± 0.05	34° ± 1	3.46 ± 0.08	30.83 ± 1.4
4	2	16	0.6	130	51	0.34 ± 0.03	38° ± 1	3.86 ± 0.10	33.12 ± 1.6
5	2	20	0.6	130	18	0.33 ± 0.01	38° ± 1	2.97 ± 0.21	39.11 ± 2.0
6	2	18	0.4	130	39	0.35 ± 0.01	36° ± 1	3.42 ± 0.12	32.56 ± 1.6
7	2	18	0.7	130	40	0.34 ± 0.01	34° ± 1	3.05 ± 0.11	38.56 ± 1.2
8	2	18	0.6	110	20	0.39 ± 0.01	36° ± 2	3.11 ± 0.17	35.16 ± 1.5
9	2	18	0.6	150	47	0.25 ± 0.06	37° ± 1	3.57 ± 0.09	34.03 ± 1.1