Scintigraphic Assessment of Drug Delivery from the Ultrahaler Dry Powder Inhaler

Abstract

A new dry powder inhaler, the Ultrahaler, has been developed to deliver nedocromil sodium for the prophylaxis of asthma. This study was performed to compare the lung deposition of nedocromil sodium inhaled from the Ultrahaler at two different inhaled flow rates with that from a pressurised metered dose inhaler (MDI). A scintigraphic study was conducted in 12 healthy volunteers. On each study day, volunteers received a single 4.2 mg dose of nedocromil sodium from the Ultrahaler, using either an optimal (fast) inhaled flow rate or a suboptimal (slow) inhaled flow rate, or two doses of 2 mg nedocromil sodium from an MDI using an optimal (slow) inhaled flow rate. Used optimally, the Ultrahaler deposited significantly more (p < 0.05) of the metered dose in the lungs than either the Ultrahaler used suboptimally or the MDI used optimally [mean (SD) lung deposition values of 13.3 (4.8)%, 9.8 (3.5)%, and 7.5 (2.9)%, respectively]. Oropharyngeal deposition averaged over 80% of the dose for all three treatment regimens. This scintigraphic study demonstrated in vivo proof of concept for the Ultrahaler dry powder inhaler, and provided quantitative data on the relationship in lung deposition between the Ultrahaler and MDI which differed from that predicted by the in vitro fine particle fraction.

Pulmonary Drug Delivery from the Taifun Dry Powder Inhaler Is Relatively Independent of the Patient's Inspiratory Effort

“…An additional feature of drug delivery from Taifun ® , not seen for most other breath-actuated DPIs, is that total and regional lung depositions were virtually independent of the degree of inspiratory effort. This situation contrasts with that observed in scintigraphic studies on most other DPIs, which show reduced lung deposition with reduced inspiratory effort for Pulvinal, (20) Turbuhaler, (14) Spinhaler, (22) Ultrahaler, (19) and AM-MDPI. (16) The reduction in lung deposition with decreasing inhalation flow through DPIs may be associated with a reduction in the clinical effects of inhaled asthma drugs.…”

In Vitro/In Vivo Correlations for Respiratory Drug Delivery

“…This observation was confirmed by the findings of another study (44) where FPF overestimated whole lung deposition from a DPI to similar degrees at both fast and slow inhaled flow rates (Fig. 3).…”

Scintigraphic comparison of budesonide deposition from two dry powder inhalers

“…While the P/C ratio detects expected changes in regional lung deposition brought about by changes in particle size for two aerosols inhaled under the identical conditions [27] the situation in the present study is compounded by the inhalation flow rate and particle size changing simultaneously. Previous scintigraphic studies involving other DPIs have also shown no change in P/C ratio with a change in flow rate, despite a change in whole lung deposition [9,10].…”

“…After removing the water by freeze drying the radiolabelled powder was put into an empty Turbuhaler. The radiolabelling method used for the AM-MDPI was broadly based upon methods developed for other drug/lactose powder blends [9,10]. Budesonide was labelled as described for the Turbuhaler, an appropriate mass of lactose added, and a Turbula 2TC mixer (Glencreston, Stanmore, UK) used to prepare a homogenous powder blend.…”