Dry powder formulation of azithromycin for COVID-19 therapeutics

Figures & data

Table 1. Mean particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency and drug loading of the two formulations (mean ± SD, n = 3).

Formulation name	Particle size (nm)	PDI	Zeta potential (mV)	Encapsulation efficiency (%)	Drug loading (%)
Azithromycin with 2% PVA solution as primary emulsion, 0.5% PVA as secondary emulsion and 0.1% PVA as dilution phase (D/2.0P/0.5P/0.1P)	464.48 ± 19.85	0.60 ± 0.04	−1.38 ± 0.12	90.62 ± 0.31	3.24 ± 0.01
Azithromycin with 2% PVA solution as primary emulsion, 0.5% PVA and 0.1% COL as secondary emulsion and 0.1% PVA as dilution phase (D/2.0P/0.5P0.1COL/0.1P)	639.03 ± 14.79	0.40 ± 0.01	29.0 ± 0.52	85.86 ± 0.33	3.73 ± 0.01

Figure 1. Transmission electron micrographs of nanoparticles of the final two formulations – (a) azithromycin formulation (33,000× magnification), (b) azithromycin formulation (93,000× magnification), (c) azithromycin and chitosan formulation (33,000× magnification), (d) azithromycin and chitosan formulation (93,000× magnification).

Figure 2. Scanning electron micrographs of spray-dried formulations – (a) azithromycin formulation without centrifugation (10,000× magnification), (b) azithromycin formulation without centrifugation (50,000× magnification), (c) azithromycin formulation with centrifugation (10,000× magnification), (d) azithromycin formulation with centrifugation (50,000× magnification), (e) azithromycin and chitosan formulation without centrifugation (10,000× magnification), (f) azithromycin and chitosan formulation without centrifugation (50,000× magnification), (g) azithromycin and chitosan formulation with centrifugation (10,000× magnification), (h) azithromycin and chitosan formulation with centrifugation (50,000 × magnification).

Table 2. X₁₀, X₅₀, X₉₀, VMD and Span value of all four formulations (mean ± SD, n = 3).

Formulation name	X10 (µm)	X50 (µm)	X90 (µm)	VMD (µm)	Span
AZI w/o	1.06 ± 0.03	2.77 ± 0.19	5.70 ± 0.26	3.50 ± 0.42	1.68 ± 0.10
AZI w/	1.40 ± 0.07	3.46 ± 0.21	7.29 ± 0.35	5.56 ± 0.25	1.71 ± 0.22
A&C w/o	1.11 ± 0.02	3.59 ± 0.28	7.39 ± 0.15	4.78 ± 0.18	1.76 ± 0.11
A&C w/	1.56 ± 0.03	3.84 ± 0.10	7.64 ± 0.22	5.69 ± 0.27	1.58 ± 0.10

Figure 3. FTIR spectrum of all raw materials and the four spray-dried formulations.

Figure 4. DSC spectrum of all raw materials and the four spray-dried formulations.

Figure 5. XRD spectrum of all raw materials and the four spray-dried formulations.

Figure 6. NGI^® deposition profile of all four formulations.

Table 3. Aerodynamic parameters of formulations delivered to the NGI^® (mean ± SD, n = 3).

Formulation name	Fraction recovered (%)	Emitted dose (%)	FPF (%)	MMAD (µm)	GSD
AZI w/o	62.53 ± 2.77	80.14 ± 4.30	41.49 ± 5.86	4.14 ± 0.20	1.86 ± 0.20
AZI w/	71.68 ± 2.99	88.06 ± 5.63	56.02 ± 2.03	4.03 ± 0.26	1.74 ± 0.04
A&C w/o	70.43 ± 2.32	81.28 ± 10.36	48.21 ± 10.22	4.02 ± 0.32	1.83 ± 0.25
A&C w/	71.48 ± 5.18	91.61 ± 1.67	60.42 ± 6.19	4.21 ± 0.31	1.78 ± 0.09