Development and evaluation of a dry powder formulation of liposome-encapsulated oseltamivir phosphate for inhalation

Figures & data

Table 1. Levels and factors in the orthogonal design.

	Factors
Levels	A (OP:PC)	B (mol/L)	C (°C)	D (min)
1	1:5	0.1	40	15
2	1:7.5	0.2	50	25
3	1:10	0.3	60	35

Table 2. The test of orthogonal design for optimization of OP liposome formulation.

	Factors
Test no.	A	B	C	D
1	1	1	1	1
2	1	2	2	2
3	1	3	3	3
4	2	1	2	3
5	2	2	3	1
6	2	3	1	2
7	3	1	3	2
8	3	2	1	3
9	3	3	2	1

Table 3. Results of the orthogonal design of OP liposomes.

	Factors
Test no.	A	B	C	D	(%)
1	1	1	1	1	23.98
2	1	2	2	2	42.6
3	1	3	3	3	48.28
4	2	1	2	3	68.65
5	2	2	3	1	68.57
6	2	3	1	2	90.31
7	3	1	3	2	72.27
8	3	2	1	3	88.72
9	3	3	2	1	79.71
K1	38.29	54.97	67.67	57.42
K2	75.85	66.63	63.65	68.40
K3	80.23	72.77	63.04	68.50
R	41.95	17.80	4.63	11.13

Table 4. The entrapment efficiency of liposomes (n = 3).

Experimental group	Entrapment efficiency (%)	Average entrapment efficiency (%)	RSD (%)
1	85.32	88.75 ± 3.09	0.03
2	89.6
3	91.32

Figure 1. TEM image of blank liposomes.

Figure 2. TEM image of OP liposomes.

Figure 3. AFM image of blank liposomes.

Figure 4. AFM image of OP liposomes.

Table 5. Particle size, polydispersity index and zeta potential of OP liposomes.

Index	OP liposomes
Particle size (nm)	105.9 ± 3.4
Polydispersity index	0.191 ± 0.012
zeta Potential (mV)	−13.65 ± 1.22

Table 6. The physical and chemical properties of liposomal OP dry powders as different ratio of l-leucine and solid content liposome.

l-Leucine/ liposome	Appearance	Yield (%)	Bulk density (mg/cm^3)	Angle of repose (°)	EE (%)
1: 1	Loose	53.24	0.23	26.1	60.43
2: 1	Coalescence	38.56	0.36	35.8	58.93
3: 1	Oalescence	25.12	0.53	45.5	57.28

Figure 5. SEM images liposomal OP dry powders.

Table 7. Properties of optimized liposomal OP dry powders formulation.

Sample	Bulk density (g/cm^3)	Particle size (μm)	Angle of repose (°)	FPF (%)	Yield (%)
Liposomal OP dry powders	0.24	3.5	29.3	35.40	55.37

Table 8. The solution of liposomes before and after spray-dried at 4 °C.

	Index
	Particle size (nm)		EE (%)
Sample	0 day	30 days	0 day	30 days
Solution of liposomal OP dry powders	165.2	180.6	69.43	61.39
Solution of OP liposomes	159.5	379.8	85.38	36.73

Table 9. Drug content uniformity of liposomal OP dry powders.

Experimental group	Theoretical drug content (%)	Measured drug content (%)	SD	RSD (%)
1	5	4.92	0.06	0.012
2	5	4.84
3	5	4.96

Figure 6. X-ray diffraction spectrum of OP.

Figure 7. X-ray diffraction spectrum of L-Lecuine.

Figure 8. X-ray diffraction spectrum of liposomal OP dry powders.

Figure 9. TEM image of blank liposomal dry powders.

Figure 10. TEM image of liposomal OP dry powders.

Figure 11. AFM image of blank liposomal dry powders.

Figure 12. AFM image of OP liposomal dry powders.

Figure 13. The curve of drug cumulative release percentage over time for different preparations.

Figure 14. Chromatography of OP in liver homogenates (A) and lung homogenates (B).

Figure 15. Regression line of v and v/[s] of liver homogenates and lung homogenates.

Figure 16. OSCA plasma concentration-time profile of group a (OP solution for oral administration) and group b (liposomal OP dry powders for pulmonary delivery).

Table 10. Pharmacokinetic analysis of OSCA following different administration (n = 5).

Groups	AUC (mg/Lċh)	AUC0–∞ (mg/Lċh)	MRT (h)	Tmax (h)	Cmax (mg/L)
Group a	4178.454 ± 929.263	4207.020 ± 321.654	4.652 ± 0.329	0.250 ± 0.052	1367.364 ± 321.5
Group b	4709.700 ± 298.518	4812.443 ± 269.321	5.608 ± 0.245	1.547 ± 0.045	1671.338 ± 533.2

Figure 17. OSCA concentrations in the lung of group c (OP solution for oral administration) and group d (liposomal OP dry powders for pulmonary delivery).