The development of dimple-shaped chitosan carrier for ethambutol dihydrochloride dry powder inhaler.
OBJECTIVE
In this study, a dimple-shaped chitosan carrier was developed for delivering the antituberculosis drug ethambutol dihydrochloride (EDH) from a dry powder inhaler (DPI) to the lungs.


METHODS
Nanosized drug particles were prepared using nanospray drying. The microsized carrier was developed from a chitosan solution by spray drying. Five formulations were prepared by physically mixing the drug and carrier in different ratios. The physico-chemical properties of the formulations were analyzed using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, ultracentrifugation and a cascade impactor.


CONCLUSIONS
The EDH size was 222 nm and the chitosan carrier size was 1.2 µm. Five formulations, i.e. 1:2, 1:2.5, 1:3.3, 1:5 and 1:10 w/w of the EDH to chitosan carrier were prepared by physical mixing. The chitosan carrier was spherical in shape with a dimpled surface and this provided shallow cavities to which the drug was bound, both within its grooves as well as on its surface. The median adhesion force (50% of drug detachment) for formulations #1 to #5 was between 122 and 993 µN. The mass median aerodynamic diameter of the EDH was between 2.3 and 2.7 μm, with the fine particle fractions (aerosolized particles less than 4.4 μm) of 32-42% of the nominal dose.


CONCLUSIONS
We suggest that ethambutol dihydrochloride mixed with a chitosan carrier was suitable for use in a dry powder inhaler for controlling tuberculosis especially in minimizing the risk of multidrug resistant tuberculosis and the possible side effects from EDH.
Department of Pharmaceutical Technology and.
Md Iftekhar
MI
Ahmad
Suwipa
S
Ungphaiboon
Teerapol
T
Srichana
D000280:Administration, Inhalation; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D058995:Dry Powder Inhalers; D004977:Ethambutol / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared
D000995:Antitubercular Agents; D004337:Drug Carriers; D004977:Ethambutol; D048271:Chitosan
Chitosan; dry powder inhaler; ethambutol dihydrochloride; microsize carrier; nanosize drug; size characterization