Development and characterization of spray-dried porous nanoaggregates for pulmonary delivery of anti-tubercular drugs

Figures & data

Table 1. Optimization of guar gum concentration.

Formulation code	Guar gum (% w/v)	Ethanol: water ratio	Average particle size (nm)	Polydispersity index (PDI)
P-GGN 1	0.1	1:1	877.55 ± 21.14	0.277 ± 0.074
P-GGN 2	0.3	1:1	882.24 ± 16.58	0.291 ± 0.084
P-GGN 3	0.5	1:1	1186.60 ± 19.85	0.466 ± 0.13
P-GGN 4	0.7	1:1	2441.29 ± 22.14	0.869 ± 0.017

Table 2. Optimization of solvent (ethanol:water) ratio.

Formulation code	Ethanol: water ratio	Guar gum (% w/v)	Particle size (nm)	Polydispersity index (PDI)
S-GGN 1	1:1	0.3	882.24 ± 16.58	0.291 ± 0.084
S-GGN 2	2:1	0.3	1394.00 ± 18.52	0.673 ± 0.024
S-GGN 3	3:1	0.3	Aggregates

Table 3. Isoniazid entrapment optimization in optimized guar gum batch (S-GGN 1).

Sl. no.	Formulation code	Drug: polymer ratio	Particle size (nm)	PDI	% entrapment
1.	I-GGN 1	1:3	1030.8 ± 24.32	0.417 ± 0.009	55.2 ± 2.41
2.	I-GGN 2	2:3	1077.9 ± 14.21	0.437 ± 0.011	51.3 ± 2.17
3.	I-GGN 3	3:3	1214.9 ± 18.23	0.484 ± 0.014	41.3 ± 1.45
4.	I-GGN 4	4:3	1271.6 ± 21.14	0.520 ± 0.021	38.3 ± 1.47
5.	I-GGN 5	5:3	1325.2 ± 25.42	0.439 ± 0.019	32.6 ± 1.14

Table 4. Rifampicin entrapment optimization in optimized guar gum batch (S-GGN 1).

Sl. no.	Formulation code	Drug polymer ratio	Particle size (nm)	PDI	% entrapment
1.	R-GGN 1	1:3	1124.0 ± 11.95	0.414 ± 0.007	52.1 ± 2.4
2.	R-GGN 2	2:3	1186.6 ± 14.2	0.466 ± 0.009	50.4 ± 2.8
3.	R-GGN 3	3:3	1283.7 ± 19.25	0.439 ± 0.012	18.2 ± 1.5
4.	R-GGN 4	4:3	1671.7 ± 27.59	0.584 ± 0.012	17.3 ± 1.9
5.	R-GGN 5	5:3	2486.1 ± 29.21	0.649 ± 0.016	13.7 ± 1.1

Table 5. Characterization of optimized formulations after spray drying.

Characterization parameters	I-GGN 2	R-GGN 2
Bulk density (g/cm^3)	0.91 ± 0.004	1.31 ± 0.010
Tapped density (g/cm^3)	1.04 ± 0.006	1.55 ± 0.015
Carr's index	16.6 ± 0.7	15.6 ± 1.2
Hausner's ratio	1.19 ± 0.02	1.18 ± 0.05
Angle of repose	24.4 ± 1.1	23.6 ± 1.5
% yield	30.3 ± 1.5	28.9 ± 2.4
Moisture content	4.51 ± 0.21	4.64 ± 0.34
Aerodynamic diameter (µm)	3.53	3.11

Figure 1. SEM images of (A) isoniazid- and (B) rifampicin-loaded guar gum porous nanoaggregates.

Figure 2. In vitro release behavior of guar gum nanoaggregates.

Figure 3. Drug distribution in different organs.

Table 6. Pharmacokinetic data of optimized formulations.

Parameters	I-GNP 2	INH	R-GNP 2	RIF
Cmax (µg/ml)	9.45 ± 1.25	5.55 ± 1.23	11.7 ± 1.38	6.65 ± 1.18
Tmax (h)	8.00 ± 1.01	2.03 ± 0.61	9.01 ± 1.42	2.89 ± 0.31
AUCtot (µg/ml/h)	174.6 ± 10.25	32.4 ± 5.25	324.5 ± 15.25	45.5 ± 3.75
t1/2 (h)	9.11 ± 1.10	2.91 ± 1.20	14.5 ± 1.12	3.7 ± 0.52
MRT (h)	16.18 ± 1.24	5.38 ± 1.4	23.5 ± 1.54	6.46 ± 1.23