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1.
Adv Drug Deliv Rev ; 191: 114580, 2022 12.
Article in English | MEDLINE | ID: mdl-36273513

ABSTRACT

Adherence to inhaled treatments is a complex challenge for patients with chronic obstructive pulmonary disease (COPD) and asthma, it not only involves following the prescribed treatment plans but also administering the medications correctly. When using a dry powder inhaler (DPI), the inhalation flow is particularly critical. Patients frequently fail to use a rapid enough onset and fast enough inhalation when using DPIs. At the same time, there is increasing pressure on physicians to switch patients to DPIs, to minimise the environmental impact of pMDI propellants. This makes it critical to understand whether a patient will maintain or improve disease control by using their new inhaler correctly. However, it is challenging for health care professionals to understand how a patient behaves away from the clinic. Therefore, it would be beneficial to obtain real-world data through the use of monitoring tools, i.e., "smart inhalers". This paper reviews the technologies used to monitor DPIs, how effective they have been in a clinical setting, and how well these have been adopted by patients and health care providers.


Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Dry Powder Inhalers , Administration, Inhalation , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/drug therapy
2.
Drug Des Devel Ther ; 14: 3043-3055, 2020.
Article in English | MEDLINE | ID: mdl-32801643

ABSTRACT

Increases in global temperature are already having a significant impact on our climate. The hydrofluorocarbon (HFC) propellants used today in pressurized metered-dose inhalers (pMDIs) have global warming potential (GWP) many times that of carbon dioxide. Their use, together with all other emissive uses of HFCs, is being phased down under the Montreal protocol. This has prompted calls to switch patients to dry powder inhalers (DPIs). This paper presents a new analysis of the top 15 respiratory drug markets by drug class. It shows that a switch to DPIs would be economically feasible for most countries and most drugs. However, a wholesale switch of reliever medications, notably short-acting  ß-agonists, would lead to significant increases in the cost of these life-saving medications. Reviewing the evidence, whilst most patients are capable of using DPIs, the very young, very old and those undergoing an acute exacerbation still require a pMDI. Thus, there is a clinical and economic need to have both pMDIs and DPIs available. At the same time, it is projected that the reduction in non-medical uses of propellants is likely to give rise to a 5-fold increase in their cost for pMDI uses and is likely to hit the Western world in 2025. This may lead to a price increase in reliever medication that will make it unaffordable for the poorer communities in some markets. At the same time, opportunities to save money by developing new formulations using propellants with lower GWP, such as HFC 152a or HFO 1234ze(E), are described. Two companies have made this commitment, but neither currently have a strong presence in reliever medication. For them, or other companies, now is the time to act; 2025 is not far away in terms of product development timescales and the climate cannot wait.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Hydrocarbons, Fluorinated/therapeutic use , Metered Dose Inhalers , Administration, Inhalation , Anti-Asthmatic Agents/administration & dosage , Dry Powder Inhalers , Humans , Hydrocarbons, Fluorinated/administration & dosage
3.
Ther Deliv ; 9(2): 121-136, 2018 02.
Article in English | MEDLINE | ID: mdl-29325508

ABSTRACT

In the 24 years since first being marketed, the mesh nebulizer has been developed by five main manufacturers into a viable solution for the delivery of high-value nebulized drugs. Mesh nebulizers provide increased portability, convenience and energy efficiency along with similar lung deposition and increased ease of use compared with jet nebulizers. An analysis of EU and US clinical trial databases has shown that mesh nebulizers are now preferred over jet nebulizers for clinical trials sponsored by pharmaceutical companies. The results show a strong preference for the use of mesh nebulizers in trials involving high cost and niche therapy areas. Built-in capability to optimize the way patients use their mesh nebulizer and manage their disease will further increase uptake. [Formula: see text].


Subject(s)
Bronchodilator Agents/administration & dosage , Drug Delivery Systems/trends , Drug Development/trends , Nebulizers and Vaporizers/trends , Administration, Inhalation , Animals , Bronchodilator Agents/chemical synthesis , Clinical Trials as Topic/standards , Drug Delivery Systems/standards , Drug Development/standards , Humans , Lung Diseases/drug therapy , Nebulizers and Vaporizers/standards
4.
Respir Care ; 63(3): 289-293, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29162718

ABSTRACT

BACKGROUND: Inhaled corticosteroids are used to treat pediatric asthma. The shaking of a pressurized metered-dose inhaler (pMDI) is required to ensure consistency of emitted dose. Delays between shaking and actuating the pMDI are frequent during administration of aerosols to children where a valved holding chamber is used. METHODS: In a recent clinical trial, we used a monitoring device to record shaking and actuation of the pMDI and the inhalation profiles of children with asthma while they were inhaling fluticasone hydrofluoroalkane from a valved holding chamber onto an external filter. During the procedure, in vitro and transport samples were generated without a delay between shaking and actuating the pMDI. Emitted dose, expressed as percentage of ex-actuator nominal dose, obtained from the second actuation following a recorded shake-actuation interval for subjects and from in vitro/transport samples (no delay) were compared. RESULTS: The mean emitted dose was 158.6% (95% CI 150.1-167.2%) (subjects) and 106.8% (95% CI 104.7-108.9%) (in vitro + transport) of the ex-actuator nominal dose (P < .001). The mean delay between shaking and actuating the pMDI was 12.9 s (95% CI 11.9-13.9 s) for the subject samples. A strong correlation was observed between shake and actuation delay and the emitted dose of the second actuation following the delay (Spearman correlation coefficient = 0.61). A 10-, 20-, and 30-s delay resulted in an emitted dose of the second actuation following the delay of 147, 187, and 227% of the ex-actuator nominal dose, respectively. CONCLUSIONS: Delays between shaking and actuating a corticosteroid suspension pMDI resulted in an increase in the emitted dose of the second actuation following the delay. This can be a common occurrence when doses are administered by a caregiver to a patient via a holding chamber. This should be addressed by practitioners educating patients and parents on proper inhaler use. (ClinicalTrials.gov registration NCT01714063.).


Subject(s)
Bronchodilator Agents/administration & dosage , Fluticasone/administration & dosage , Metered Dose Inhalers , Administration, Inhalation , Aerosols , Asthma/drug therapy , Child , Child, Preschool , Female , Humans , Hydrocarbons, Fluorinated , Male , Pressure , Random Allocation , Time Factors
5.
Ther Deliv ; 8(6): 391-399, 2017 06.
Article in English | MEDLINE | ID: mdl-28470113

ABSTRACT

In the later half of the 20th century, nebulized therapy was in decline, but in the 21st century the prospects for the expanded use of nebulized therapy within respiratory medicine look bright. The advent of mesh nebulizers, which combine the universal applicability of the nebulizer in the treatment of all respiratory patients with the convenience of portable inhaler use, is ideally timed to capitalize on the forecast of increased numbers of patients who will require nebulized therapy in the future. This special report will highlight some of the opportunities that the development of mesh nebulizers presents in the field of respiratory medicine.


Subject(s)
Bronchodilator Agents/administration & dosage , Drug Delivery Systems , Nebulizers and Vaporizers , Pulmonary Medicine/trends , Administration, Inhalation , Aerosols , Humans
6.
J Aerosol Med Pulm Drug Deliv ; 30(1): 71-79, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27635793

ABSTRACT

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) should be shaken before use to prevent creaming or sedimentation of the drugs in solution; however, data published on this topic are limited, and it is rarely specified how soon after shaking the device should be actuated. Delays between shaking and firing the pMDI have previously been shown to cause significant inhomogeneity in delivered dose. We studied the effect of various shake-fire delays on the drug delivered from five commercially available pMDIs commonly prescribed for asthma and chronic obstructive pulmonary disease to assess the potential variability in delivered dose. METHODS: The pMDI formulations tested were the Flovent HFA, Ventolin Evohaler, Airomir Inhaler, and Symbicort (suspension pMDIs), and the QVAR 100 Inhaler (solution pMDI). Each pMDI was shaken for 5 seconds before attachment to a dosage unit sampling apparatus collection tube and filter, and it was actuated once with shake-fire delays of 0, 5, 10, 20, 30, 40, 50, and 60 seconds. Analysis of the eluates from the collection tubes and filters was performed by using high-performance liquid chromatography. Three of each pMDI were tested twice with each time delay. RESULTS: All of the suspension pMDIs produced variable amounts of drug over the shake-fire delays tested. A comparison of the delivered doses after the 0- and 60-second delays showed that the drug delivered increased for the Flovent HFA (320%), Ventolin Evohaler (346%), and Airomir Inhaler (230%) pMDIs; decreased for the Symbicort budesonide (75%) and formoterol fumarate (76%) pMDI; and remained consistent for the QVAR 100 Inhaler pMDI. CONCLUSIONS: The amount of drug delivered can vary widely over different shake-fire delays with suspension pMDIs. Therefore, guidance should be given to users/caregivers on the timing of firing after shaking their device, particularly with pediatrics, who may take time to become receptive to accepting their medication after pMDI shaking and before dose administration.


Subject(s)
Anti-Asthmatic Agents/administration & dosage , Bronchodilator Agents/administration & dosage , Drug Delivery Systems , Metered Dose Inhalers , Administration, Inhalation , Chromatography, High Pressure Liquid , Equipment Design , Humans , Time Factors , Tissue Distribution
7.
J Aerosol Med Pulm Drug Deliv ; 30(1): 1-13, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27537608

ABSTRACT

This article reports on discussions at the 2015 workshop cosponsored by the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) and the International Society for Aerosols in Medicine (ISAM), entitled "Regulatory and Patient Considerations for Inhalation Device Design, Development and Use." Key topics addressed at the workshop and presented here include patient-focused device design for orally inhaled products (OIPs), instructions for use (IFU), human factors, regulatory considerations in the United States and Europe, development of generic inhalers, quality-by-design, and change management of OIP devices. Workshop participants also identified several areas for further consideration and emphasized the need for increased focus on the patient to create therapeutic products (inclusive of device design, IFU, education, training) that support adherence with an individual patient's treatment regimen. Advances in patient-centric product development will require engagement and collaboration by industry, regulators, patients, physicians, and other stakeholders. The article includes summaries of presented talks as well as of panel and audience discussions.


Subject(s)
Equipment Design , Medical Device Legislation , Nebulizers and Vaporizers , Administration, Inhalation , Aerosols , Europe , Humans , Pharmaceutical Preparations/administration & dosage , United States
8.
Int J Pharm ; 496(2): 1069-72, 2015 Dec 30.
Article in English | MEDLINE | ID: mdl-26475968

ABSTRACT

Nebulized treatment is an important delivery option for the young, elderly, and those with severe chronic respiratory disease, but there is a lack of new nebulized drug products being produced for these patients, leading to the potential for under-treatment. This communication describes a new drug development paradigm as a timely solution to this issue. Often, drug development is initiated with nebulizers in the early stages, to provide cheaper and faster drug development, and then switched to inhaler devices in later clinical trials to address the majority of patients. However, the waste of resource on parallel development of the inhaler can be large due to the high early attrition rate of new drug development. The new paradigm uses the nebulizer to continue drug development through to market, and initiates inhaler development after completion of the riskier early phase studies. New drug safety and efficacy can be assessed faster and more efficiently by using a nebulized formulation rather than developing an inhaler. The results of calculations of expected net present value showed that the new paradigm produced higher expected net present values than the conventional model over a range of economic scenarios. This new paradigm could therefore provide improved returns on investments, as well as more modern drugs in nebulized form for those patients unable to use inhalers.


Subject(s)
Drug Discovery , Nebulizers and Vaporizers , Administration, Inhalation , Chemistry, Pharmaceutical , Drug Discovery/economics
9.
Expert Opin Drug Deliv ; 12(11): 1755-65, 2015.
Article in English | MEDLINE | ID: mdl-26067581

ABSTRACT

INTRODUCTION: Respiratory diseases remain a target for improved forms of inhalation therapy. However, there are neither regulatory preferences for one type of device over another, nor well-recognized guidelines. This guidance describes factors that should be considered to optimize the choice of delivery system. AREAS COVERED: This article summarizes the different types of delivery systems with key technical and commercial considerations for selection. It highlights current market trends and opportunities for the future, based on the author's experience of more than 20 years in this field. EXPERT OPINION: For a generic drug, low device cost favors a capsule dry powder inhaler (DPI) or a propellant-based metered-dose inhaler (pMDI). Novel particle engineering approaches may allow close matching to the innovator product performance. For novel drugs, most companies favor a bespoke DPI, adding patent protection and aiding brand recognition, despite being expensive to develop. Device features may add differentiation, but "no outcome, no income." Patient technique and adherence remain problematic, compounded by age, although accessories, including monitors, can help. There are few modern medicines available in nebulized form, so there is value in fast-tracking the nebulized formulations from Phase I studies through to market in parallel to the chosen inhaler.


Subject(s)
Drug Delivery Systems , Respiratory Tract Diseases/drug therapy , Administration, Inhalation , Dry Powder Inhalers , Humans , Metered Dose Inhalers
10.
Expert Opin Drug Deliv ; 12(8): 1375-87, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25758911

ABSTRACT

INTRODUCTION: Nebulizers are a common device choice for use when developing a new drug product, but the range of nebulizer devices available can make it difficult to select the right device. Increasingly, companies are only able to promote a drug with the device that was used during the development program; therefore, choosing the best device at an early stage is important in order to achieve commercial success. Selecting a device that is inappropriate for the intended drug can result in poor drug delivery from the nebulizer to the patient, which would have obvious implications for the development program. As device performance varies, it is important to ensure that the most appropriate device is chosen for the intended drug to ensure optimal drug delivery to the patient population. AREAS COVERED: In this review, the types of nebulizer devices available are highlighted, and the factors that should be taken into consideration when selecting the most appropriate device for a new drug are discussed. The review is broadly divided into drug, device, patient and trial characteristics. EXPERT OPINION: Efficient nebulizer devices that combine electronic monitoring capabilities as a form of telehealth are likely to provide superior drug delivery to patients and accurate clinical trial data. Their use in adaptive clinical trials may help to vastly reduce the time and costs associated with achieving drug approval.


Subject(s)
Aerosols/administration & dosage , Drug Delivery Systems , Nebulizers and Vaporizers , Humans
11.
J Aerosol Med Pulm Drug Deliv ; 28(2): 69-81, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25548863

ABSTRACT

Despite the availability of effective treatments for respiratory disorders, disease control is often suboptimal, due in part to the failure of patients to adhere to prescribed regimens, or to demonstrate competence with the often complex steps in the administration of inhaled medications. The cost of poor true adherence, a combined measure of adherence and inhaler competence, is considerable, both economically and in terms of health-related impact. While patient education is recognized as essential, there exist many barriers to healthcare professional-led monitoring and promotion of true adherence. Successful intervention remains a challenging task, dependent upon understanding and addressing the distinct issues associated with poor adherence and inhaler competence, and lessening the perceived burden on healthcare professionals. Electronic monitors provide an accurate and objective indication of adherence and may also be of value in assessing inhaler competence. The information provided by such devices is a helpful aid to understanding the challenging nature of true adherence, and may be crucial to the development and assessment of true adherence promoting interventions. This article provides a background to the impact of suboptimal adherence and inhaler competence, and the challenges associated with the promotion of true adherence, with an emphasis on respiratory therapies. Contemporary electronic monitors of adherence and inhaler competence are critically reviewed, and case studies of emerging technologies are provided to illustrate the use of innovative monitoring devices in the promotion of true adherence in practice. Potential future directions, including increased targeting and individualization, enhanced coordination of care, and a greater focus on inhaler competence are considered to be important additions to currently available technologies in this rapidly evolving field.


Subject(s)
Medication Adherence , Nebulizers and Vaporizers , Reminder Systems/instrumentation , Respiratory System Agents/administration & dosage , Telemetry/instrumentation , Administration, Inhalation , Attitude of Health Personnel , Equipment Design , Feedback, Psychological , Health Knowledge, Attitudes, Practice , Humans , Patient Education as Topic , Treatment Outcome
12.
Ther Deliv ; 5(12): 1261-73, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25531928

ABSTRACT

A wide range of asthma and chronic obstructive pulmonary disease products are soon to be released onto the inhaled therapies market and differentiation between these devices will help them to gain market share over their competitors. Current legislation is directing healthcare towards being more efficient and cost-effective in order to continually provide quality care despite the challenges of aging populations and fewer resources. Devices and drugs that can be differentiated by producing improved patient outcomes would, therefore, be likely to win market share. In this perspective article, the current and potential opportunities for the successful delivery and differentiation of new inhaled drug products are discussed.


Subject(s)
Anti-Asthmatic Agents/administration & dosage , Asthma/drug therapy , Drug Delivery Systems/methods , Drug Industry/organization & administration , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Anti-Asthmatic Agents/economics , Asthma/economics , Cost-Benefit Analysis , Drug Delivery Systems/economics , Drug Industry/economics , Drug Substitution/economics , Drug Substitution/methods , Humans , Medication Adherence , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive/economics , Research Design , Technology, Pharmaceutical , Telemedicine/organization & administration
13.
Pharm Res ; 22(10): 1692-9, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16180127

ABSTRACT

PURPOSE: Quantification of inhaled aerosols by planar gamma scintigraphy could be improved if a more comprehensive assessment of aerosol distribution patterns among lung airways were obtained. The analysis of planar scans can be quite subjective because of overlaying of small, peripheral airways with large, conducting airways. Herein, a computer modeling technique of the three-dimensional (3-D) branching structure of human lung airways was applied to assist in the interpretation of planar gamma camera images. METHODS: Airway dimensions were derived from morphometric data, and lung boundaries were formulated from scintigraphy protocols. Central, intermediate, and peripheral regions were superimposed on a planar view of the 3-D simulations, and airways were then tabulated by type, number, surface area, and volume in each respective region. RESULTS: These findings indicate that the central region, for example, consists mostly of alveolated airways. Specifically, it was found that alveolated airways comprise over 99% of the total number of airways, over 95% of the total airway surface area, and approximately 80% of the total airway volume in the central region. CONCLUSIONS: The computer simulations are designed to serve as templates that can assist in the interpretation of aerosol deposition data from scintigraphy images.


Subject(s)
Computer Simulation , Gamma Cameras , Lung/anatomy & histology , Lung/diagnostic imaging , Models, Theoretical , Lung Volume Measurements , Pulmonary Alveoli/anatomy & histology , Pulmonary Alveoli/diagnostic imaging , Radionuclide Imaging
14.
J Allergy Clin Immunol ; 112(1): 29-36, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12847476

ABSTRACT

BACKGROUND: The coadministration of long-acting inhaled beta(2)-agonists and inhaled corticosteroids is the most effective treatment for persistent asthma. OBJECTIVE: This meta-analysis aimed to determine the efficacy of fluticasone propionate and salmeterol inhaled from a single inhaler (combination therapy) or from separate inhalers (concurrent therapy). METHODS: Four similarly designed double-blind studies individually confirmed equivalence between combination and concurrent therapy on the basis of the primary efficacy measure (morning peak expiratory flow [PEF]). Each study showed a consistent trend in favor of combination therapy. Individual patient data from these studies were combined to provide overall estimates of treatment effect for morning PEF and other efficacy measures. RESULTS: Fixed-effects meta-analysis showed a significant advantage for combination therapy compared with concurrent therapy in morning PEF (mean difference between groups in change from baseline over 12 weeks of 5.4 L/min; P =.006; 95% CI = 1.5-9.2). Logistic regression analysis showed that the odds of achieving a greater than 15 or greater than 30 L/min improvement with combination therapy were increased by approximately 40% compared with those after concurrent therapy (15 L/min: odds ratio = 1.42, P =.008, 95% CI = 1.1-1.8; 30 L/min: odds ratio = 1.40, P =.006, 95% CI = 1.1-1.8), representing an additional 7% to 9% and 5% to 14% more patients, respectively, on combination therapy responding compared with those on concurrent therapy. CONCLUSION: The meta-analysis indicates that the fluticasone propionate plus salmeterol combination offers the potential for increased clinical efficacy over concurrent use of the same doses of the same 2 drugs. After administration from a single inhaler, fluticasone propionate and salmeterol might codeposit in the airways. It is hypothesized that this codeposition offers an increased opportunity for synergistic interaction to occur.


Subject(s)
Albuterol/analogs & derivatives , Albuterol/administration & dosage , Androstadienes/administration & dosage , Asthma/drug therapy , Administration, Inhalation , Albuterol/pharmacokinetics , Androstadienes/pharmacokinetics , Asthma/physiopathology , Drug Synergism , Drug Therapy, Combination , Fluticasone , Humans , Lung/physiopathology , Nebulizers and Vaporizers , Salmeterol Xinafoate
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