Effect of Texture and Surface Chemistry on Deagglomeration and Powder Retention in Capsule-Based Dry Powder Inhaler.

Pulmonary delivery systems should administer a high dose of the required formulation with the designated dry powder inhaler (DPI) to achieve therapeutic success. While the effects of device geometry and individual components used on powder dispersion are described in literature, potential effects of DPI surface properties on powder retention within the device and deagglomeration have not been adequately studied, but could impact inhalation therapy by modifying the available dose. For this, inner parts of a model DPI were modified by plasma treatment using various processes. Since both the hydrophilic-hydrophobic and structural properties of the surface were altered, conclusions can be drawn for future optimization of devices. The results show that surface topography has a greater influence on powder deposition and deagglomeration than hydrophilic or hydrophobic surface modification. The most important modification was observed with an increased rough surface texture in the mouth piece, resulting in lower powder deposition in this part (from 5 to 1% quantified amount of powder), without any change in powder deagglomeration compared to an untreated device. In summary, increasing the surface roughness of DPI components in the size range of a few nanometers could be an approach for future optimization of DPIs to increase the delivered dose.

State of the Art in Capsule-Based Dry Powder Inhalers: Deagglomeration Techniques and the Consequences for Formulation Aerosolization.

Commercially available dry powder inhalers (DPIs) are usually devices in a fixed combination with the intended formulation, and a change in medication by the physician often forces the patient to use a different device, requiring the patient to relearn how to use it, resulting in lower adherence and inadequate therapy. To investigate whether DPIs can achieve successful outcomes regardless of the formulation and flow rate used, a novel DPI and two commercially available devices were compared in vitro for their deagglomeration behavior for different binary blends and a spray-dried particle formulation. The results demonstrate that the novel device achieved the highest fine particle fraction (FPF) regardless of the formulations tested. In the binary mixtures tested, the highest emitted fraction was obtained by shaking out the powder due to the oscillating motion of the capsule in the novel device during actuation. For DPIs with high intrinsic resistance to airflow, similar FPFs were obtained with the respective DPI and formulation, regardless of the applied flow rate. Additionally, the development and use of binary blends of spray-dried APIs and carrier particles may result in high FPF and overcome disadvantages of spray-dried particles, such as high powder retention in the capsule.

Comparative bioavailability of two hydrofluoroalkane formulations of formoterol fumarate both delivered by pressurised metered dose inhaler.

A randomised, open-label, single dose, four-period crossover study was performed in healthy male human subjects to compare the pharmacokinetics of formoterol fumarate (CAS 43229-80-7) after inhalation from two different hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) formulations at two dose levels, 12 and 24 microg. This is the first study which has evaluated two HFA formulations of formoterol. Fourteen subjects were randomised, of which 13 completed the study. Each subject received in separate periods a single dose of 12 microg or 24 microg of each formulation. Blood samples for determination of formoterol plasma concentrations were taken pre-administration of study treatments and subsequently at 2, 5, 10, 20, 30, 45, 60, 90 min and 2, 3, 4, 6, 8, 12, 24 and 36 h post-administration of the study treatments. The pharmacokinetic profiles of both the formulations were similar in shape and a dose-related increase in formoterol plasma concentration was seen at all time points for both the test and reference formoterol HFA formulations between the dose levels 12 microg and 24 microg. Overall, the findings indicate that treatment with the test formoterol HFA preparation has a lung absorption pattern and systemic exposure comparable to the already licensed reference formoterol HFA preparation.