An Investigation into the Powder Release Behavior from Capsule-Based Dry Powder Inhalers

Figures & data

FIG. 1. Relationship between airflow rate and generated pressure drop for low- (LR) and high-resistance (HR) RS01® inhalers, with and without a capsule. Coefficient of correlation values were greater than 0.996 for all regression lines.

TABLE 1 Pressure drop measurements, with and without capsule, for low-resistance (LR) and high-resistance (HR) RS01® inhalers at 30, 60, and 90 L min⁻¹ flow rate

Flow rate (L min^−1)	Without capsule (kPa)		With capsule (kPa)
	LR	HR	LR	HR
30	0.50	1.50	0.30	1.10
60	1.80	5.50	1.40	4.10
90	3.80	10.80	2.90	8.30

FIG. 2. Emitted dose as a function of pressure drop for low- and high-resistance RS01® inhalers (n = 5; mean ± SD).

FIG. 3. Influence of flow rate and presence of a capsule on the mean cumulative volumetric particle size distributions of aerosolized mannitol powder measured from Malvern Spraytec® at (a) 30, (b) 60, and (c) 90 L min^–1 (n = 3).

TABLE 2 Corresponding volume medium diameter (X₅₀) of aerosolized dose measured from Malvern Spraytec® (n = 3; mean ± SD) without and with capsule

Device	Flow rate (L min^−1)	Without capsule	With capsule
LR	30	8.91 ± 1.48	5.97 ± 0.75
	60	8.07 ± 1.26	4.41 ± 0.23
	90	7.16 ± 0.29	4.21 ± 0.08
HR	30	8.97 ± 2.18	5.01 ± 0.39
	60	7.68 ± 0.46	4.36 ± 0.24
	90	6.59 ± 0.42	5.64 ± 1.89

FIG. 4. Typical example illustrating changes in X50 transmission profiles of mannitol powder dispersed with and without capsule from the low-resistance RS01® inhaler at 90 L min^–1.

FIG. 5. Typical example showing the obscuration profiles of mannitol powder dispersed with and without capsule from low resistance at 90 L min^–1.

TABLE 3 Powder obscuration data tabulating %PO and t_po parameters (n = 3; mean ± SD)

Device	Flow rate (L min^−1)	Without capsule		With capsule
		%PO	tPO (ms)	%PO	tPO (ms)
LR	30	73.5 ± 1.58	103.5 ± 5.72	37.2 ± 4.82	579.6 ± 215.4
	60	88.2 ± 1.19	48.4 ± 4.87	63.8 ± 7.10	186.7 ± 62.50
	90	90.2 ± 1.01	34.7 ± 4.16	72.2 ± 4.90	105.5 ± 49.90
HR	30	77.8 ± 5.04	102.3 ± 6.50	61.3 ± 8.32	204.9 ± 98.70
	60	85.0 ± 3.01	73.1 ± 2.34	69.6 ± 2.53	146.0 ± 41.0
	90	88.1 ± 1.335	51.1 ± 1.514	66.6 ± 11.2	114.9 ± 51.9

TABLE 4 Dependency values and coefficient correlation for each estimated parameter for the initial release and single-decay rate models (n = 3; mean ± SD)

Flow rate (L min^−1)		Initial release (sigmoidal) model				Single-rate decay model
		%PO′	tempty (s)	t50 (s)	R^2	Ao	Kdm (s^−1)	Bo	R^2
Without capsule	LR30	0.80 ± 0.09	0.57 ± 0.10	0.73 ± 0.13	0.989 ± 0.006	0.65 ± 0.011	0.70 ± 0.009	0.23 ± 0.035	0.849 ± 0.055
	LR60	0.72 ± 0.12	0.50 ± 0.11	0.64 ± 0.15	0.988 ± 0.008	0.61 ± 0.021	0.68 ± 0.042	0.27 ± 0.100	0.945 ± 0.041
	LR90	0.65 ± 0.03	0.41 ± 0.01	0.54 ± 0.06	0.997 ± 0.001	0.63 ± 0.005	0.72 ± 0.009	0.36 ± 0.038	0.980 ± 0.003
	HR30	0.54 ± 0.07	0.33 ± 0.06	0.41 ± 0.08	0.994 ± 0.002	0.67 ± 0.078	0.73 ± 0.046	0.24 ± 0.144	0.872 ± 0.035
	HR60	0.59 ± 0.16	0.38 ± 0.14	0.47 ± 0.19	0.989 ± 0.004	0.63 ± 0.035	0.68 ± 0.018	0.21 ± 0.043	0.968 ± 0.007
	HR90	0.53 ± 0.18	0.33 ± 0.15	0.40 ± 0.18	0.990 ± 0.005	0.66 ± 0.004	0.75 ± 0.008	0.39 ± 0.033	0.978 ± 0.009
With capsule	LR30	0.47 ± 0.38	0.33 ± 0.44	0.38 ± 0.41	0.954 ± 0.025	0.86 ± 0.010	0.90 ± 0.018	0.55 ± 0.20	0.963 ± 0.017
	LR60	—	—	—	—	0.77 ± 0.058	0.84 ± 0.031	0.50 ± 0.028	0.980 ± 0.009
	LR90	—	—	—	—	0.74 ± 0.064	0.82 ± 0.063	0.49 ± 0.143	0.985 ± 0.008
	HR30	0.70 ± 0.14	0.48 ± 0.15	0.59 ± 0.18	0.980 ± 0.005	0.71 ± 0.059	0.78 ± 0.036	0.40 ± 0.125	0.976 ± 0.013
	HR60	0.82 ± 0.13	0.61 ± 0.14	0.75 ± 0.12	0.984 ± 0.007	0.76 ± 0.052	0.81 ± 0.028	0.39 ± 0.052	0.970 ± 0.015
	HR90	—	—	—	—	0.76 ± 0.08	0.84 ± 0.055	0.53 ± 0.148	0.965 ± 0.013

^a Experimental data could not be converged to Equation (1)[1] .

^b Only two sample experiments converged to Equation (1)[1] .

FIG. 6. Initial obscuration profiles of individual experiments from the low-resistance RS01® at 90 L min^–1 (a) without, and (b) with a capsule.

FIG. 7. Influence of pressure drop on the estimated rate constant parameters for (a) time constant, t_empty, and (b) single-decay rate constant, K_dm (n = 3; mean ± SD).

FIG. 8. Scatter plots showing the effect of estimated parameters (a) t_empty, and (b) K_dm on X₅₀ from the low- and high-resistance RS01®.