Low powder mass filling of dry powder inhalation formulations.
BACKGROUND
The successful accurate dosing and filling of powders at fill masses of <10 mg is considered to be challenging for the pharmaceutical industry. This is mainly due to the limitations of current powder volumetric dosing technologies, which rely on formulations having 'good' flow properties. This is especially true for dry powder inhaler (DPI) applications where, together with good manufacturability, powders must also exhibit properties that allow acceptable product performance.


OBJECTIVE
In this study, the OMNIDOSE® filling technology was investigated for its capability to accurately fill powders suitable for DPI applications, to masses as low as 1 mg.


RESULTS
Several lactose monohydrate-based powders were successfully dosed at target fill masses of 1 and 5 mg using the current technology at laboratory scale. The filling behavior of the excipients could be related to various aspects of their physical properties. DPI formulations were dosed at masses of 4 and 25 mg at pilot scale to produce capsules that exhibited aerosolization fine particle fractions of ∼30% based on label claim.


CONCLUSIONS
Initial studies suggest that the OMNIDOSE((®)) technology is readily adaptable for the dosing of low masses of DPI excipients and formulations and demonstrate the value of thoroughly evaluating powder performance at laboratory scale prior to pilot scale.
Eskandar
Fadi
F
Novartis Pharma AG, PDU Inhalation, Basel, Switzerland. fadi.eskandar@novartis.com
Lejeune
Morgane
M
Edge
Stephen
S
D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D058995:Dry Powder Inhalers / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry*
D005079:Excipients; D011208:Powders; D007785:Lactose