Capsule-based Dry Powder Inhaler Research Articles

Interaction of Formulation and Device Factors Determine the In Vitro Performance of Salbutamol Sulphate Dry Powders for Inhalation

A variety of capsule-based dry powder inhalers were used to evaluate formulation-device interaction. The in vitro deposition of salbutamol sulphate (SS) was compared directly to published data for salmeterol xinafoate (SX). A 3(2) factorial design was used to assess the effect of SS formulations with three blends of different grade coarse lactose supplemented with different levels of fine lactose. These formulations were tested for homogeneity and evaluated for their in vitro deposition using Aeroliser, Handihaler and Rotahaler devices. The performance of the SS-lactose formulations differed across the grade of lactose and amount of fine lactose used compared to the same powder compositions blended with SX. SX had a greater fine particle fraction than SS for most of the comparable formulations, probably because of the different cohesiveness of the drugs. A head-to-head comparison of 'matched' SX and SS formulations when aerosolised from the same three devices demonstrated that formulation-device interactions are as critical in determining the in vitro deposition of drug-lactose blends as the identity of the active pharmaceutical ingredient. This work has revealed the limitations of the interpretative value of published in vitro performance data generated with a single device (even at equivalent aerosolisation force), when designing formulations for a different device.

An Investigation into the Powder Release Behavior from Capsule-Based Dry Powder Inhalers

A methodology for studying the deagglomeration performance and emptying behavior of micronized mannitol powder from two commercial capsule-based dry powder inhalers (DPIs), the low- and high-resistance RS01®, is presented. Mathematical modeling played a key role in the interpretation of the powder release behavior from these two DPI systems. Non-linear regression models, which were characterized from the aerosol obscuration versus time profiles obtained from laser diffraction particle sizing data, were used to estimate rate constants for emptying of mannitol powder. The effects of device resistance and associated pressure drops, sampling flow rate, rates of powder emptying, and the presence of capsule on the dispersion characteristics were studied. The presence of a capsule significantly improved the aerosolization performance of mannitol powder from both inhalers, which may be due to the extended powder–air–device interactions within the device. It is important to consider the stochastic nature of moveme...

“Pierce and inhale” design in capsule based dry powder inhalers: Effect of capsule piercing and motion on aerodynamic performance of drugs

In this work three capsule-based dry powder inhalers, available for generics product development, were compared. Two technologically different dry powder formulations were used in order to relate the capsule piercing position and motion in the device to their aerodynamic performance.A “pierce and inhale” design, in which the capsules pierced with RS01, HandiHaler or Turbospin devices were aerosolized in the same device or transferred and aerosolized with another device, was constructed and carried out.The results obtained showed that two dry powder formulations, i.e., a drug/lactose blend or a carrier-free powder, aerosolized using capsule based inhalers, performed differently. The aerosolization of drug carrier mixture in terms of drug dispersion and emitted dose, was more sensible to the piercing and device combination than the carrier free powder. The motion of the capsule during the aerosolization boosted the powder emission, whereas the powder disaggregation was more influenced by the airflow pattern around the capsule and inside the inhaler turbulence chamber.

Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium

Objectives:The long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) has recently been approved as a once-daily treatment for COPD. The objectives of this study were to determine the dose delivery characteristics of glycopyrronium and compare them with those of the LAMA tiotropium, both delivered by their respective capsule-based dry-powder inhalers (DPIs).Research design and methods:Seven inhalation profiles derived from patients with moderate and severe COPD were reproduced to determine the aerodynamic particle size distribution of glycopyrronium delivered by the Breezhaler device, a low-resistance DPI. Theoretical respiratory tract deposition was estimated using a semi-empirical model for healthy lungs. These results were compared with those of tiotropium delivered by the high-resistance HandiHaler device obtained in a previous study using the same set of inhalation profiles. Study limitations are that fine particle fraction (FPF) and particle size are generated by the inhalers are not a direct measure of lung deposition, and the bronchodilator effect of inhaled drugs does not depend solely upon the percentage of the total dose that reaches the lung.Results:The mean FPF (≤4.7 µm) was 42.6% of the nominal dose (which refers to the content of the capsule) for glycopyrronium and 9.8% for tiotropium while the mass median aerodynamic diameter (MMAD) was 2.8 µm and 3.9 µm for glycopyrronium and tiotropium, respectively. The mean estimated intrathoracic drug deposition as a percentage of the mean dose delivered to the Next Generation Impactor was 39% for glycopyrronium and 22% for tiotropium.Conclusions:The glycopyrronium capsule-based DPI delivered a higher FPF and greater and more consistent intrathoracic deposition irrespective of age and disease severity compared to the tiotropium capsule-based DPI, suggesting that it may be suitable for use by patients with a wide range of COPD severities.

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

This study investigated the effect of modifying the design of the Cyclohaler on its aerosolization performance and comparability to the HandiHaler at multiple flow rates. The Cyclohaler and HandiHaler were designated as model test and reference unit-dose, capsule-based dry powder inhalers (DPIs), respectively. The flow field, pressure drop, and carrier particle trajectories within the Cyclohaler and HandiHaler were modeled via computational fluid dynamics (CFD). With the goal of achieving in vitro comparability to the HandiHaler, the CFD results were used to identify key device attributes and to design two modifications of the Cyclohaler (Mod 1 and Mod 2), which matched the specific resistance of the HandiHaler but exhibited different cyclonic flow conditions in the device. Aerosolization performance of the four DPI devices was evaluated by using the reference product's capsule and formulation (Spiriva capsule) and a multistage cascade impactor. The in vitro data showed that Mod 2 provided a closer match to the HandiHaler than the Cyclohaler and Mod 1 at 20, 39, and 55l/min. The in vitro and CFD results together suggest that matching the resistance of test and reference DPI devices is not sufficient to attain comparable aerosolization performance, and the improved in vitro comparability of Mod 2 to the HandiHaler may be related to the greater degree of similarities of the flow rate of air through the pierced capsule (Q(c)) and the maximum impact velocity of representative carrier particles (V(n)) in the Cyclohaler-based device. This investigation illustrates the importance of enhanced product understanding, in this case through the CFD modeling and in vitro characterization of aerosolization performance, to enable identification and modification of key design features of a test DPI device for achieving comparable aerosolization performance to the reference DPI device.

Insulin-micro- and nanoparticles for pulmonary delivery

The pulmonary application of insulin via oral inhalation turned out to be a promising option due to the large surface area and good vascularisation the lung is offering for the systemic delivery of peptides and proteins. To have a systemic effect, inhaled particles need to attain the alveoli and should therefore have a mass median diameter of less than 2 μm. To achieve such a particle size for dry powders spray drying of drug solutions is a common method. In this study, a nano-precipitation of the drug prior to spray drying was carried out using the solvent change method. The produced powders were compared to powder produced out of a solution and to the marketed product Exubera ®. The Aerolizer ® device was used representing a simple capsule-based dry powder inhaler. It could be shown that the insulin yield of the precipitation process highly depends on the used pH-value and the amount of non-solvent. Also the particle size after spray drying decreases with increasing amount of non-solvent. Aerodynamic assessment of insulin powders showed that the precipitated insulin particles behave superior to powders spray dried from solution with respect to particles smaller than 2 μm. The deposition pattern of the originator powder delivered with the Exubera ® device showed significantly lower fine particle fractions and higher residues in comparison to the Aerolizer ® device. In summary, precipitated insulin particles combined with the delivery from a standard capsule-based inhaler were found to be at least as effective in vitro as the marketed Exubera ® product. With an optimised powder having an increased particle fraction smaller than 2 μm more insulin may reach the deeper lung. Therefore, a lower dose could be used for an effective diabetic therapy.