Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro–in silico lung deposition results

Figures & data

Table 1. Compositions of the DPI formulations containing the applied concentration of excipients.

Products	CIP (w/w %)	NaSt (w/w %)	IH 70 (w/w %)	MgSt (w/w %)
µCIP + IH70	9.09	–	90.91	–
CIP_0.5NaSt_spd	99.50	0.50	–	–
CIP_0.5NaSt_spd + IH70_MgSt	9.045	0.045	88.91	2.00

Figure 1. Structural investigation of the formulations by XRPD before and after storage.

Table 2. Residual solvent content in the samples.

Products	Residual solvent content (%)
	Before storage	1 month
µCIP + IH70	0.492 ± 0.009	0.518 ± 0.006
CIP_0.5NaSt_spd	0.175 ± 0.002	0.218 ± 0.110
CIP_0.5NaSt_spd + IH70_MgSt	0.500 ± 0.005	0.490 ± 0.003

Table 3. Cohesion, adhesion values, and spreading coefficient of the preparations.

Samples	Wc (mN/m)		Wadh (mN/m)		Fadh (mN)		S21
	Before storage	1 month	Before storage	1 month	Before storage	1 month	Before storage	1 month
µCIP	161.60 ± 0.26	160.06 ± 0.66	‒	‒	‒	‒	‒	‒
µCIP + IH70	‒	‒	108.26 ± 0.56	107.39 ± 0.77	1.690 × 10^–3 ± 0.09 × 10^–3	1.677 × 10^–3 ± 0.15 × 10^–3	1.64 ± 0.08	2.38 ± 0.13
CIP_0.5NaSt_spd	123.26 ± 0.89	144.74 ± 1.13	‒	‒	‒	‒	‒	‒
CIP_0.5NaSt_spd + IH70_MgSt	‒	‒	72.57 ± 1.26	81.81 ± 0.98	0.504 × 10^–3 ± 0.11 × 10^–3	0.593 × 10^–3 ± 0.07 × 10^–3	‒19.06 ± 0.23	–49.1 ± 0.36

Table 4. Morphology and particle size distribution of the formulations during the storage.

Samples	Before storage			10 days			1 month
	D [0.1] (µm)	D [0.5] (µm)	D [0.9] (µm)	D [0.1] (µm)	D [0.5] (µm)	D [0.9] (µm)	D [0.1] (µm)	D [0.5] (µm)	D [0.9] (µm)
µCIP + IH70
	15.034 ± 0.16	156.028 ± 1.85	198.152 ± 1.73	25.550 ± 0.26	170.366 ± 0.86	257.835 ± 1.19	31.846 ± 0.22	180.277 ± 1.81	285.720 ± 1.36
CIP_0.5NaSt_spd
	1.208 ± 0.05	2.364 ± 0.11	4.556 ± 0.09	1.494 ± 0.02	2.466 ± 0.06	5.321 ± 0.04	1.608 ± 0.07	2.981 ± 0.12	23.123 ± 0.08
CIP_0.5NaSt_spd + IH70_MgSt
	3.245 ± 0.12	128.763 ± 0.78	194.180 ± 0.63	4.513 ± 0.08	137.106 ± 1.15	221.555 ± 1.26	5.830 ± 0.02	158.440 ± 1.78	278.396 ± 1.36

Table 5. FPF value of microparticles before and after storage.

Samples	Before storage	10 days	1 month
µCIP + IH70
FPF <5 µm (%)	23.30 ± 0.23	17.57 ± 0.45	15.55 ± 0.36
FPF <3 µm (%)	11.88 ± 0.20	8.67 ± 0.36	7.83 ± 0.18
CIP_0.5NaSt_spd
FPF <5 µm (%)	54.27 ± 2.75	39.41 ± 1.91	30.22 ± 1.82
FPF <3 µm (%)	27.14 ± 2.38	17.43 ± 0.96	12.72 ± 1.66
CIP_0.5NaSt_spd + IH70_MgSt
FPF <5 µm (%)	63.75 ± 1.21	57.36 ± 2.21	47.12 ± 0.78
FPF <3 µm (%)	39.22 ± 0.74	33.56 ± 0.96	26.52 ± 1.12

Table 6. EF and MMAD values of microparticles before and after storage.

Products	Before storage	10 days	1 month
µCIP + IH70
EF (%)	96.92 ± 0.11	95.56 ± 0.22	96.52 ± 0.45
MMAD (µm)	7.98 ± 0.10	10.02 ± 0.15	11.40 ± 0.23
CIP_0.5NaSt_spd
EF (%)	76.99 ± 3.32	92.23 ± 0.21	92.32 ± 0.19
MMAD (µm)	4.14 ± 0.18	5.48 ± 0.28	6.54 ± 0.05
CIP_0.5NaSt_spd + IH70_MgSt
EF (%)	90.45 ± 1.80	90.65 ± 0.32	89.46 ± 1.12
MMAD (µm)	3.47 ± 0.02	4.03 ± 0.19	5.47 ± 0.35

Figure 2. In silico lung modeling results of the novel combined formulated DPI, SD< ±3%. ET: extrathoracic airways; LUNG: bronchial and acinar parts; EXH: exhalation fraction.