Table I.
Characterization of Particle Sizes by Laser Diffraction for the Reference and Test Formulations and Lactose
| Formulation | Drug particle size (D50), μm | Lactose brand and grade | Drug concentrationa (RSD %),b albuterol base, % w/w | Volume diameter (SDc), μm | Lactose fine content,d % | |||
|---|---|---|---|---|---|---|---|---|
| D10 | D50 | D90 | (D90–D10)/D50 | Mean (SD) | ||||
| Reference (Rotacaps) | – | Milled | 0.820 (3.76) | 2.78 (0.09) | 39.9 (1.10) | 97.3 (1.85) | 2.37 (0.02) | 20.9 (0.48) |
| A | 1.9 | Respitose ML003, milled | 0.797 (0.925) | 3.48 (0.05) | 34.4 (0.32) | 102 (0.32) | 2.86 (0.02) | 22.9 (0.25) |
| B | 1.9 | Lactohale LH 200, milled | 0.773 (0.984) | 6.67 (0.11) | 73.2 (0.39) | 161 (0.37) | 2.11 (0.01) | 12.4 (0.10) |
| C | 3.2 | Respitose ML003, milled | 0.785 (0.887) | 3.85 (0.04) | 35.3 (0.43) | 107 (0.94) | 2.91 (0.01) | 22.0 (0.21) |
| D | 3.2 | Lactohale LH 200 + LH 300, millede | 0.729 (0.967)f | 3.13 (0.02) | 58.7 (1.53) | 144 (3.37) | 2.40 (0.01) | 24.0 (0.31) |
| Lactose only | Respitose ML003, milled | 4.00 (0.07) | 35.7 (0.40) | 106 (2.94) | 2.84 (0.05) | 20.8 (0.19) | ||
| Lactose only | Lactohale LH 200, milled | 9.97 (0.08) | 74.9 (0.30) | 158 (1.89) | 1.97 (0.02) | 10.0 (0.07) | ||
| Lactose only | Lactohale LH 300, micronized | 0.77 (0.01) | 3.54 (0.03) | 8.91 (0.03) | 2.30 (0.05) | 93.0 (0.08) | ||
aThe mean of six measurements (25 mg per sample) in terms of albuterol base
bRelative standard deviation
cStandard deviation
dPercentage below 10 μm
e8.0 % Lactohale LH 300
fFormulation D was formulated 8.9 % below target albuterol concentration. For exploratory purposes, performance of the lower concentration formulation was studied in an attempt to offset the greater dispersion efficiency of the test product