Real-life budesonide and formoterol dose emission from the medium and high strength fixed dosed combinations in a Spiromax® dry powder inhaler using inhalation profiles from patients with chronic obstructive pulmonary disease

Abstract

Dry powder inhalers (DPIs) are passive devices used to administer inhaled medication for the management of asthma and chronic obstructive pulmonary disease (COPD). DPIs require patients to generate a sufficient internal turbulent airflow force during each inhalation to deaggregate the powdered drug formulation into an emitted dose containing particles with the greatest likelihood of lung deposition. This internal force is generated by the interaction between the user's inhalation flow and the resistance of the DPI. Traditional compendial in vitro methods of measuring dose emission use a vacuum pump to simulate inhalation. We have adapted this in vitro method by replacing the square wave inhalation profile generated by a vacuum pump with the inhalation profiles of patients using an empty DPI. This method enables accurate assessment of the actual dose they would have inhaled. In the present study, real-life inhalation profiles were selected from 15 patients with COPD who inhaled through an empty placebo Spiromax ® DPI. Ex vivo dose emissions were measured for the medium (emitted dose of 160 µg/4.5 µg) and high-strength (320 µg/9 µg) budesonide/formoterol formulations from the Spiromax DPI. These profiles were used to investigate the effect of the primary inhalation parameterpeak inhalation flow (PIF). Some profiles were modified to isolate other inhalation parameters (namely, inhaled volume [Vin] and acceleration rate of the inhalation maneuver [ACIM]). Both the medium-strength and high-strength DuoResp Spiromax displayed flow-dependent dose emission. When the PIF of a patient's inhalation maneuver increased from 26.8 L/min to 69.7 L/min, there was a significant (p < 0.05) effect on the dose-emission characteristics of the medium-strength and high-strength DuoResp Spiromax. At each PIF, an increase in Vin from approximately 500 mL to 2,000 mL had no effect on the dose-emission characteristics of either strength. However, at each Vin there was a significant (p < 0.05) effect on the dose-emission characteristics as PIF increased. The effect of ACIM on the dose-emission characteristics was small. The ex vivo methodology used in this study provides a practical approach to identify the actual dose a patient might inhale during routine real-life use of the DuoResp Spiromax.

Effect of different doses of Budesonide combined with Tiotropium bromide inhalation on elderly patients with chronic obstructive pulmonary disease

“…While current studies show clinical value of budesonide combined with tiotropium bromide in the treatment of COPD, 24 there is no unified standard for the optimal dosage of Budesonide. 15,16 Our study clearly shows that medium and high doses of Budesonide can improve disease treatment effect and ensure treatment safety. We may speculate that as the dosage of the medication increases, the local drug concentration rises, making it more effective in targeting the lesion and continuously exerting its efficacy.…”

“…The incidence of adverse reactions in both groups was low, which indicates the safety of high-dose budesonide. Bagherisadeghi et al 15 also confirmed that increasing the dosage of budesonide has certain positive impact on improving the pulmonary function rehabilitation effect of patients with COPD, and does not correlate with higher incidence of adverse reactions. Qi et al 16 showed that the optimal dose of budesonide for patients with COPD in China is 4-6 mg/d.…”

“…The administration of medium and high doses of budesonide can improve the overall clinical effect of the treatment better than small doses, and the increase of drug dosage is not associated with an increased risk of adverse reactions. 14,15 Hanania et al 14 used high-dose and low-dose budesonide to treat patients with COPD, and showed that the improvement of lung function and acute attack in patients treated with high dose of the drug were better compared to the low-dose group. The incidence of adverse reactions in both groups was low, which indicates the safety of high-dose budesonide.…”

“…The administration of medium and high doses of budesonide can improve the overall clinical effect of the treatment better than small doses, and the increase of drug dosage is not associated with an increased risk of adverse reactions. 14 , 15 …”