Delivery of Dry Powders to the Lungs: Influence of Particle Attributes from a Biological and Technological Point of View

2019 ◽  
Vol 16 (3) ◽  
pp. 180-194 ◽  
Author(s):  
Sarah Zellnitz ◽  
Eva Roblegg ◽  
Joana Pinto ◽  
Eleonore Fröhlich
Keyword(s):  
Solid State ◽  
Dry Powder Inhaler ◽  
Point Of View ◽  
Dry Powder Inhalers ◽  
Dry Powder ◽  
Dry Powders ◽  
Pharmaceutical Ingredients ◽  
Technical Requirements ◽  
Particle Characteristics ◽  
Epithelial Cell Layer

Dry powder inhalers are medical devices used to deliver powder formulations of active pharmaceutical ingredients via oral inhalation to the lungs. Drug particles, from a biological perspective, should reach the targeted site, dissolve and permeate through the epithelial cell layer in order to deliver a therapeutic effect. However, drug particle attributes that lead to a biological activity are not always consistent with the technical requirements necessary for formulation design. For example, small cohesive drug particles may interact with neighbouring particles, resulting in large aggregates or even agglomerates that show poor flowability, solubility and permeability. To circumvent these hurdles, most dry powder inhalers currently on the market are carrier-based formulations. These formulations comprise drug particles, which are blended with larger carrier particles that need to detach again from the carrier during inhalation. Apart from blending process parameters, inhaler type used and patient’s inspiratory force, drug detachment strongly depends on the drug and carrier particle characteristics such as size, shape, solid-state and morphology as well as their interdependency. This review discusses critical particle characteristics. We consider size of the drug (1-5 µm in order to reach the lung), solid-state (crystalline to guarantee stability versus amorphous to improve dissolution), shape (spherical drug particles to avoid macrophage clearance) and surface morphology of the carrier (regular shaped smooth or nano-rough carrier surfaces for improved drug detachment.) that need to be considered in dry powder inhaler development taking into account the lung as biological barrier.

scholarly journals REVIEW ON DRY POWDER INHALERS: CURRENT ADVANCES AND LIMITATIONS

2021 ◽  
pp. 63-67
Author(s):  
A. V. Badarinath ◽  
S A Sreenivas ◽  
M. Suresh Babu
Keyword(s):  
Clinical Practice ◽  
Focal Point ◽  
Dry Powder Inhaler ◽  
Dry Powder Inhalers ◽  
Clinical Use ◽  
Expected Loss ◽  
Dry Powder ◽  
Everyday Clinical Practice ◽  
Innovative Work

Inhalers are the focal point of quickened innovative work as a result of the possibility to deliver greatest medication to the site of pathology in the lungs. Among the accessible conveyance choices, the dry powder inhaler (DPI) is the favoured gadget for the treatment of an undeniably different scope of ailments. Advancement of DPI frameworks that focus on the conveyance of fine medication particles to the more profound aviation routes in the lungs utilizing a mix of improved medication definitions and upgraded conveyance gadget advances implies that every one of these variables adds to in general execution of the vaporized framework. There are enormous scopes of gadgets for clinical use, anyway no individual gadget shows prevalent clinical viability. A significant worry that is pertinent in everyday clinical practice is the between and intra-understanding fluctuation of the medication measurements conveyed to the profound lungs from the inward breath gadgets, where the degree of changeability relies upon the medication definition, the gadget plan, and patient's breath profile. This fluctuation may result in under-dosing of medication to the patient and expected loss of pharmacological viability. This article audits ongoing advances in container based DPI innovation and the presentation of the 'dispensable' DPI gadget.

scholarly journals Development of an adaptive bypass element for passive entrainment flow control in dry powder inhalers

2019 ◽  
Vol 233 (15) ◽  
pp. 5201-5213
Author(s):  
Thomas Kopsch ◽  
Darragh Murnane ◽  
Digby Symons
Keyword(s):  
Drug Delivery ◽  
Dry Powder Inhaler ◽  
Experimental Methods ◽  
Dry Powder Inhalers ◽  
Total Flow ◽  
Dry Powder ◽  
Flow Rates ◽  
Inhaler Device ◽  
Flow Resistances ◽  
Flap Valve

The release of drug from dry powder inhalers is strongly dependent on the patient's inhalation profile. To maximise the effect of the treatment, it is necessary to optimise dry powder inhalers to achieve drug delivery that (A) is independent of the inhalation manoeuvre and (B) is targeted to the correct site in the lung. The purpose of this study is to develop a dry powder inhaler with an adaptive bypass element that achieves desired drug delivery behaviour. Computational and experimental methods are used. First, the effect of a generic variable bypass element on entrainment behaviour is modelled. This is done by modelling a dry powder inhaler as a network of flow. Second, the behaviour of a potential variable bypass element, a flap valve, is studied both computationally and experimentally. Third, the flow resistances are optimised to achieve consistent and desired entrainment behaviour for patients with very different inhalation manoeuvres. A simulated dry powder inhaler device design was found that achieves an approximately constant entrainment flow rate of 12 L/min when total flow rates larger than 20 L/min are applied. The developed dry powder inhaler is predicted to accurately deliver drug for patients with highly different inhalation manoeuvres.

A Preference Study of Two Placebo Dry Powder Inhalers in Adults with COPD: ELLIPTA® Dry Powder Inhaler (DPI) versus DISKUS® DPI

2015 ◽  
Vol 13 (2) ◽  
pp. 167-175 ◽  
Author(s):  
Suyong Yun Kirby ◽  
Chang-Qing Zhu ◽  
Edward M. Kerwin ◽  
Richard H. Stanford ◽  
George Georges
Keyword(s):  
Dry Powder Inhaler ◽  
Dry Powder Inhalers ◽  
Dry Powder ◽  
Preference Study

scholarly journals The Use of a Three-Fluid Atomising Nozzle in the Production of Spray-Dried Theophylline/Salbutamol Sulphate Powders Intended for Pulmonary Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1116
Author(s):  
Stefano Focaroli ◽  
Guannan Jiang ◽  
Peter O'Connell ◽  
John V. Fahy ◽  
Anne-Marie Healy
Keyword(s):  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Spray Dryer ◽  
Equivalent Formulation ◽  
Dry Powders ◽  
Salbutamol Sulphate ◽  
Pharmaceutical Ingredients ◽  
Low Solubility ◽  
Two Fluid ◽  
Spray Dried

The aim of this study was to investigate the use of a three-fluid atomising nozzle in a lab-scale spray dryer for the production of dry powders intended for pulmonary delivery. Powders were composed of salbutamol sulphate and theophylline in different weight ratios. The three-fluid nozzle technology enabled powders containing a high theophylline content to be obtained, overcoming the problems associated with its relatively low solubility, by pumping two separate feed solutions (containing the two different active pharmaceutical ingredients (APIs)) into the spray dryer via two separate nozzle channels at different feed rates. The final spray-dried products were characterized in terms of morphology, solid-state properties and aerosolization performance, and were compared with an equivalent formulation prepared using a standard two-fluid atomising nozzle. Results confirmed that most of the powders made using the three-fluid atomising nozzle met the required standards for a dry powder inhaler formulation in terms of physical characteristics; however, aerosolization characteristics require improvement if the powders are to be considered suitable for pulmonary delivery.

scholarly journals The Use of Video Instructions in Patient Education Promoting Correct Technique for Dry Powder Inhalers: An Investigation on Inhaler-Naïve Individuals

Pharmacy ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 106 ◽  
Author(s):  
Sofia von Schantz ◽  
Nina Katajavuori ◽  
Anne Juppo
Keyword(s):  
Disease Management ◽  
Dry Powder Inhaler ◽  
Dry Powder Inhalers ◽  
Inhaler Technique ◽  
Dry Powder ◽  
Educational Method ◽  
Inhaler Device ◽  
Correct Technique ◽  
Study Participants ◽  
To Receive

Introduction: The correct use of a prescribed inhaler device is crucial for achieving successful disease management in asthma. This study investigates non-verbal, demonstrational videos as a method of teaching inhaler naïve individuals how to use a dry powder inhaler (DPI). Methods: Video instructions for four DPIs were examined using a mixed methodology; 31 inhaler-naïve individuals participated in the study. Participants were each shown a demonstrational video of one the four inhalers, after each video the participant demonstrated how they would use the inhaler. After demonstrating the use, participants crossed over to the next inhaler. The demonstrations were videotaped. A common questionnaire was filled at the beginning of the study and four inhaler-specific questionnaires which were filled out by the participant after each inhaler demonstration. Results: The frequency of participant error varied between inhalers. When asked about how they perceived the video instructions, participants often stated they would have liked to receive feedback on their performance. The importance of feedback was further highlighted by the fact that participants tended to overestimate their own inhaler technique. Conclusion: Non-verbal videos may be more efficient for some DPIs than for others as a method for providing inhaler instructions. Lack of feedback on the participants’ inhaler performance emerged as a clear shortcoming of this educational method. Some steps in the inhalation process may be harder for individuals to remember and therefore require extra emphasis in order to achieve correct inhaler technique.

Quantifying Uncertainty in the Residence Time of the Drug and Carrier Particles in a Dry Powder Inhaler

2021 ◽  
Author(s):  
Antara Badhan ◽  
V M KRUSHNARAO Kotteda ◽  
Samia Afrin ◽  
Vinod Kumar
Keyword(s):  
Residence Time ◽  
Particle Density ◽  
Dry Powder Inhaler ◽  
Department Of Energy ◽  
Dry Powder ◽  
Throat Region ◽  
Particle In Cell ◽  
Pharmaceutical Ingredients ◽  
Fluidizing Agent ◽  
The Individual

Abstract Dry powder inhalers, used as a means for pulmonary drug delivery, typically contain a combination of active pharmaceutical ingredients (API) and significantly larger carrier particles. The micro-sized drug particles - which have a strong propensity to aggregate and poor aerosolization performance - are mixed with significantly large carrier particles that cannot penetrate the mouth-throat region to deagglomerate and entrain the smaller API particles in the inhaled airflow. Therefore, a DPI's performance depends on the carrier-API combination particles' entrainment and the time and thoroughness of the individual API particles' deagglomeration from the carrier particles. Since DPI particle transport is significantly affected by particle-particle interactions, particle sizes and shapes present significant challenges to CFD modelers to model regional lung deposition from a DPI. We employed the Particle-In-Cell method for studying the transport/deposition and the agglomeration and deagglomeration for DPI carrier and API particles in the present work. The proposed development will leverage CFD-PIC and sensitivity analysis capabilities from the Department of Energy laboratories: Multiphase Flow Interface Flow Exchange and Dakota UQ software. A data-driven framework is used to obtain the reliable low order statics of the particle's residence time in the inhaler. The framework is further used to study the effect of drug particle density, carrier particle density and size, fluidizing agent density and velocity, and some numerical parameters on the particles' residence time in the inhaler.

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