Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

Figures & data

Table 1. Effect of adding different concentrations of ethanol in 0.9% saline on nebulization rate/min and nebulized fraction (mean ± S.D., n = 6).

	Ethanol-saline (%)
Nebulization rate/min	0	10	20	30	40	50
1st min	5.6 ± 0.8%	5.6 ± 0.7%	5.8 ± 0.8%	8.6 ± 0.8%	8.0 ± 0.6%	7.2 ± 0.5%
10th min	5.1 ± 0.7%	5.2 ± 0.6%	5.7 ± 0.8%	8.5 ± 0.8%	8.0 ± 0.7%	6.9 ± 0.5%
15th min	5.1 ± 0.8%	5.1 ± 0.7%	Dry	Dry	Dry	Dry
Nebulized fraction (%)	30.5 ± 3.3	39.2 ± 3.6	55.3 ± 6.5	67.8 ± 7.6	68.4 ± 8.2	69.3 ± 8.5

Table 2. Andersen cascade impactor (ACI) results for AS nebulization with and without spacer at inspiratory flow rate of 28.3 L min⁻¹ (n = 6).

	ACI (inhalation indices)
Particle size attributes	Without spacer	With spacer
Particle size (nm)	900–1200	350–500
Emitted dose (%)	68.2 ± 8.5*	46 ± 7.4
Respiratory fraction (%)	65.2 ± 5.2	82.6 ± 3.1*
Small particle fraction (%)	32 ± 2.6	56.4 ± 4.8*
Total recovery (%)	97.7 ± 0.78	97.4 ± 1.41

Data are expressed as mean ± S.D.

*p < 0.05.

Table 3. Signs and symptoms of atropinization in human volunteers after inhalation of submicronic 3% AS respiratory fluid (n = 6).

Time (min)	5 min			10 min			15 min			30 min			60 min			120 min
Signs of atropinization	Dry mouth	Thirst	Blurred vision	Dry mouth	Thirst	Blurred vision	Dry mouth	Thirst	Blurred vision	Dry mouth	Thirst	Blurred vision	Dry mouth	Thirst	Blurred vision	Dry mouth	Thirst	Blurred vision
Volunteer 1	–	–	–	–	–	–	–	–	–	++	++	+	++	++	++	+	+	–
Volunteer 2	–	–	–	+	+	+	+	+	++	++	++	++	++	++	++	++	+	+
Volunteer 3	+	–	–	+	+	–	+++	+	+	+++	++	+++	++	++	+++	++	+	+
Volunteer 4	–	–	–	–	–	–	+	+	+	++	++	++	++	++	++	+	+	–
Volunteer 5	+	–	–	+	+	–	++	+	+	+++	++	++	++	++	+	+	+	+
Volunteer 6	–	–	–	–	–	–	+	+	+	++	++	+	++	++	++	+	+	–

– No symptom; + Mild; ++ Moderate; +++ Severe.

Figure 1. Plasma concentrations of 3% nano-AS in human volunteers post-nebulization (mean ± S.D., n = 6).

Figure 2. Human scintigraphy images of submicronic 3% AS respiratory formulation in two healthy volunteers at 5 min and 2 h showing distribution of the drug into oral cavity, tracheobronchial tree, lungs and stomach. While (a) represents distribution of nebulized drug using a spacer, (b) represent distribution of drug without a spacer.

Table 4. Gamma scintigraphy based regional deposition of AS aerosols after inhalation of submicronic 3% AS respiratory fluid containing tracer quantity of ^99mTc-DTPA (200–300 μCi) in human volunteers (n = 6).

Variables	Percent drug deposition Post-nebulization
Nebulizer cup	31.4 ± 2.8
Spacer, mouthpiece and T-Piece	13.3 ± 2.5
Exhalation filter	7.1 ± 1.1
Emitted dose	49.2 ± 6.5
Whole lung	80.2 ± 6.8
(a) Centre	(a) 33.6 ± 4.3
(b) Intermediate	(b) 28.3 ± 1.5
(c) Peripheral	(c) 18.3 ± 1.1
P/C ratio	0.54

Data are presented as mean ± S.D. Whole-lung deposition is the sum of central, intermediate, and peripheral values and represents percentage of inhaled dose.