Influence of Peak Inspiratory Flow Rates and Pressure Drops on Inhalation Performance of Dry Powder Inhalers (original) (raw)
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Pharmaceutical Research, 2010
Purpose To construct a simple simulator reproducing human inspiratory flow patterns and use it to evaluate the inhalation performance of active ingredient particle-carrier particle systems (physically mixed dry powders). Methods Inspiratory flow patterns were collected and analyzed using a flow recorder. The simulator was constructed using an airtight container, a valve, and a connecting tube. Several of the patterns reproduced by the simulator were compared with those recorded. In addition, the influence of inspiratory flow on the inhalation performance of physically mixed dry powders composed of salbutamol sulfate (SS) and coarse lactose monohydrate was investigated using a twinstage liquid impinger (TSLI) equipped with the simulator. Results Human inspiratory flow patterns could be characterized by three parameters: inspiratory flow volume (area under the flow rate-time curve (AUC)), flow increase rate (FIR), and peak flow rate (PFR). The patterns could be reproduced using the simulator. Testing with the simulator in vitro revealed that PFR, but not FIR or AUC, greatly affected the inhalation performance of physically mixed dry powders. Conclusions The simulator is simple to construct and can schematically reproduce human inspiratory flow patterns. Testing with a TSLI and the simulator is useful to evaluate dry powder formulations for clinical application. KEY WORDS dry powder inhaler. inhaler testing. inspiratory flow pattern. physically mixed dry powders. twin-stage liquid impinger (TSLI)
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2019
Dry powder inhalers (DPIs) all have the ability to aerosolize dry powders, but they each offer different operating mechanisms and resistances to inhaled airflow. This variety has resulted in both clinician and patient confusion concerning DPI performance, use, and effectiveness. Particularly, there is a growing misconception that a single peak inspiratory flow rate (PIFR) can determine a patient's ability to use a DPI effectively, regardless of its design or airflow resistance. For this review article, we have sifted through the relevant literature concerning DPIs, inspiratory pressures, and inspiratory flow rates to provide a comprehensive and concise discussion and recommendations for DPI use. We ultimately clarify that the controlling parameter for DPI performance is not the PIFR but the negative pressure generated by the patient's inspiratory effort. A pressure drop * ‡1 kPa (*10 cm H 2 O) with any DPI is a reasonable threshold above which a patient should receive an adequate lung dose. Overall, we explore the underlying factors controlling inspiratory pressures, flow rates and dispensing, and dispersion characteristics of the various DPIs to clarify that inspiratory pressures, not flow rates, limit and control a patient's ability to generate sufficient flow for effective DPI use.
Understanding Dry Powder Inhalers: Key Technical and Patient Preference Attributes
Advances in Therapy
Inhalable medications for patients with asthma and chronic obstructive pulmonary disease (COPD) can be confusing even for health care professionals because of the multitude of available devices each with different operating principles. Dry powder inhalers (DPI) are a valuable option for almost all of the patients with asthma or COPD. Based on recorded patient inspiratory profiles, the peak inspiratory flow requirement of 30 L min-1 of high-resistance devices does not usually pose any practical limitations for the patients. Suboptimal adherence and errors in device handling are common and require continuous checking and patient education in order to avoid these pitfalls of all inhalation therapy. The aim of this opinion paper is to describe the working principles of DPIs and to summarise their key properties in order to help prescribing the correct inhaler for each patient.
Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers
The AAPS Journal, 2012
The study examined the sensitivity of DPI in vitro performance to formulation and device changes. Rotahaler/Rotacaps was selected as the reference DPI drug product, and Aerolizer was selected as the test device. Since the test device was recognized to have much greater efficiency of dispersion, simple modifications to both formulation and device were made in an effort to provide a closer match to the in vitro performance of the reference product. The modifications included varying the drug and lactose particle sizes and/or lactose fine particle content in the test formulations, as well as lowering the specific resistance of the test device. These modifications were intended to address variables important for drug product performance for a defined experimental design and were not intended to mimic the extensive formulation and device design strategies that are employed in an industrial setting. Formulation and device modifications resulted in a modified test product that approached the reference product in the in vitro performance.
Formulation and Evaluation of Dry Powder Inhaler
International Journal for Research in Applied Science & Engineering Technology (IJRASET), 2022
This review focuses on the dry powder inhaler (DPI) formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency. This review thus demonstrates that the successful delivery of dry powder aerosols to the lung requires careful consideration of the powder production process, formulation and inhaler device. The developments and improvements towards high dose powder pulmonary drug delivery are summarized and discussed here. It also throws light on the invention and improvement of novel inhaler devices as well as the further development of formulation principles and new powder engineering methods. I. INTRODUCTION OF DRY POWDER INHALER Inhalation drug delivery has been used for many years for the delivery of pharmacologically active agents to treat respiratory disease .Traditional asthma therapy with bronchodilators, steroids, mast cell stabilizers, and anticholinergic drugs has primarily used the pressurized metered-dose inhaler (MDI). However, this delivery system is now under increasing threat because of the environmental concerns regarding chlorofluorocarbon (CFC) propellants. A range of alternative devices, such as dry powder inhalers, which do not contain propellants, are being evaluated and developed. [1] Dry powder inhalers contain the drug in a powder formulation, where drug particles (< 5 μm) are blended with a suitable large carrier (e.g. lactose) to improve flow properties and dose uniformity and drug powders are delivered into the deep lung via a device known as dry powder inhaler (DPI). Powder de-agglomeration and aeroionisation from these formulations are achieved by the patient's inspiratory airflow. In a DPI, the aerosol needs to be generated from the powder formulation by patient 'sown effort'. For achieving this, a high turbulence is needed to break the large agglomerates of the drug into smaller, finer and inhalable particles. Turbulence is generated by creating resistance to air flow in the DPI device and the effort required to generate adequate flow rates is dependent on the extent of resistance. Whereas the flow rates required to be generated vary among various available DPIs, a flow rate of 60-90 L/min is generally required. Pulmonary drug delivery by Dry Powder Inhalers (DPIs), by virtue of its propellant free nature, high patient compliance, high dose carrying capacity, drug stability and patent protection, has encouraged rapid development in recent past to realize full potential of lungs for local and systemic treatment of diseases. But DPIs are complex in nature and their performance relies on many aspects including the design of inhaler, the powder formulation and the airflow generated by the patient. In last decade, performance of DPIs has improved significantly through the use of engineered drug particles and modified excipient systems. Exploration of inhalation aerosols for drug delivery has contributed vastly in treating pulmonary diseases for decades.Interestingly, inhalation of powders has been used for many centuries dating back to ancient times by the ancient Egyptians and Greeks. In the 19th century, Newton and Nelson each patented a DPI, after which the inhalation aerosol therapy took a detour away from DPI until 1948, when Abbott introduced Aerohalor for penicillin. Although drug delivery through inhalation was achieved many years ago, dose control was poor. When the pharmaceutical industry succeeded in delivering controlled doses of drug, there was no looking back. Treatment of pulmonary diseases, especially asthma, was revolutionized. Today, drug delivery has come a long way in successfully delivering drug to the lungs not only for local action but also for systemic application. Yet, inhalation aerosol drug delivery faces challenge in achieving consistent dose delivery and toxicity related to higher dosages delivered to the lungs. The four major classes of inhalation aerosol delivery systems are nebulizers, pMDIs and DPIs. Each has its own advantages, disadvantages and limitations in regard to the type of formulation that can be used, the types of drugs that can be used, and the amount of respirable dose that can be generated from these devices. In the past two decades, respiratory drug delivery has focused on two main aspects of drug delivery: replacing chlorofluorocarbon propellants and methodology to increase drug bioavailability.
AAPS PharmSciTech, 2017
The permeability of a powder bed reflects its particle size distribution, shape, packing, porosity, cohesivity, and tensile strength in a manner relevant to powder fluidization. The relationship between the permeability and the performance of carrier-based dry powder inhalation (DPI) mixtures has, however, aroused controversy. The current study sought to gain new insights into the relationship and to explore its potential applications. We studied eight lactose materials as DPI carriers. The carriers covered a broad permeability range of 0.42-13.53 D and moreover differed in particle size distribution, particle shape, crystal form, and/or porosity. We evaluated the performance of inhalation mixtures of each of these carriers and fluticasone propionate after aerosolization from an Aerolizer®, a model turbulent-shear inhaler, at a flow rate of 60 L/min. Starting from the high permeability side, the inhalation mixture performance increased as the carrier permeability decreased until optimum performance was reached at permeability of~3.2 D. Increased resistance to air flow strengthens aerodynamic dispersion forces. The inhalation mixture performance then decreased as the carrier permeability further decreased. Very high resistance to air flow restricts powder dispersion. The permeability accounted for effects of carrier size, shape, and macroporosity on the performance. We confirmed the relationship by analysis of two literature permeability-performance datasets, representing measurements that differ from ours in terms of carrier grades, drug, technique used to determine permeability, turbulent-shear inhaler, and/or aerosolization flow rate. Permeability provides useful information that can aid development of DPI mixtures for turbulent-shear inhalers. A practical guidance is provided.
A REVIEW ON DEVELOPMENT OF DRY POWDER INHALER
A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device. This review focuses on the DPI formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency.
Influence of carrier on the performance of dry powder inhalers
International Journal of Pharmaceutics, 2007
The aim of this work is to study carriers which can become alternatives to monohydrate lactose in dry powder inhalers and to consider particle parameters that influence adhesion between drug and carrier in dry powder inhalers.
[Patient preference in the choice of dry powder inhalers]
2004
Inhalable medications for patients with asthma and chronic obstructive pulmonary disease (COPD) can be confusing even for health care professionals because of the multitude of available devices each with different operating principles. Dry powder inhalers (DPI) are a valuable option for almost all of the patients with asthma or COPD. Based on recorded patient inspiratory profiles, the peak inspiratory flow requirement of 30 L min-1 of high-resistance devices does not usually pose any practical limitations for the patients. Suboptimal adherence and errors in device handling are common and require continuous checking and patient education in order to avoid these pitfalls of all inhalation therapy. The aim of this opinion paper is to describe the working principles of DPIs and to summarise their key properties in order to help prescribing the correct inhaler for each patient.
The clinical relevance of dry powder inhaler performance for drug delivery
Respiratory medicine, 2014
Although understanding of the scientific basis of aerosol therapy with dry powder inhalers (DPIs) has increased, some misconceptions still persist. These include the beliefs that high resistance inhalers are unsuitable for some patients, that extra fine (<1.0 μm) particles improve peripheral lung deposition and that inhalers with flow rate-independent fine particle fractions (FPFs) produce a more consistent delivered dose to the lungs. This article aims to clarify the complex inter-relationships between inhaler design and resistance, inspiratory flow rate (IFR), FPF, lung deposition and clinical outcomes, as a better understanding may result in a better choice of DPI for individual patients. The various factors that determine the delivery of drug particles into the lungs are reviewed. These include aerodynamic particle size distribution, the inspiratory manoeuvre, airway geometry and the three basic principles that determine the site and extent of deposition: inertial impaction, ...