Articles

Spray drying is used to produce engineered, inhalable dry powders and is a critical tool for new drug developers. It enables production of powders with a tightly controlled range of particle sizes and solid-state properties. Formulators have control over the crystalline and amorphous character and radial distribution of components and particle morphology. This comes from understanding the impact of each material’s physicochemical properties and the kinetics of droplet drying.

Much improvement has taken place in evaluating sources of variability in the measures of delivered dose uniformity (DDU) and aerodynamic particle size distribution (APSD). Methods described in the United States Pharmacopeia (USP) and European Pharmacopoeia (Pharm. Eur.) now include dimensions and diagrams for all components critical to their robustness. However, we show that there are sources of bias in the standard methods for DDU. A future article will address APSD.

The Biopharmaceutics Focus Group of the Academy of Pharmaceutical Sciences (APS) of Great Britain presented a workshop on nasal biopharmaceutics at the 2022 Drug Delivery to the Lungs Conference (DDL2022) in December 2022 in Edinburgh, UK. The aim was to bring together the scientific community to discuss challenges in the development of nasally administered therapies.

Following “lower than expected demand,” Nestlé is exploring strategic options for Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp], the first and only drug approved by the US FDA for the treatment of peanut allergy in children.

The Food Allergy Bravery Clinic at Children’s Hospital of Philadelphia provides cognitive behavioral therapy to children who have severe food allergy-related anxiety, helping them reduce their fears and improve their quality of life.

When selecting biological models for testing inhalation products, careful consideration must be made regarding the area of the respiratory tract that is the target site for a product. Once the appropriate cellular models are selected, there are several cell culture techniques that can be utilized to mimic the physiologically relevant conditions.

Excipient enhanced growth (EEG) is progressing through toxicological studies and showing promise for treatment of asthma and lung cancer by delivering active molecules to target sites in the lungs. This article discusses development of two candidates, budesonide and gemcitabine, for local lung delivery using this formulation approach in combination with traditional spray drying for the generation of respirable engineered particles.

The United States Centers for Disease Control and Prevention (CDC) has published a report in the Annals of Allergy, Asthma and Immunology that offers recommendations and resources to assist allergists and immunologists in supporting patients as they become affected by climate change.

Climate change may have more severe effect on children’s health, according to a review published in the New England Journal of Medicine by researchers from Stanford University and Columbia University. In two interviews, one of the authors discussed the content of the review.

In spray-dried formulations, various excipients or carriers are incorporated to improve the aerosolization behavior, stability and mechanical properties of active pharmaceutical ingredients (APIs) as well as to modify the pharmacokinetics and pharmacodynamics of APIs. Sugars are the most common excipients used as diluents and flow enhancers. In addition, sugars can provide hydrogen bonding and act as product stabilizers when water is removed.

With the increasing prevalence and use of digital technologies applied to drug delivery devices and software solutions to support inhaled therapeutics, there are multiple considerations that patients, healthcare professionals, payors and pharmaceutical manufacturers can and should observe. Key considerations include identifying the stakeholders required, value to deliver to each stakeholder, system design and the laws and regulations with which the system must comply.

The SABINA study of SABA inhaler usage and risk of asthma exacerbations, funded by AstraZeneca, is the largest real-world observational data analysis of asthma inhaler therapy and has evaluated more than one million patients across 40 countries. In addition, at Queen Mary University of London, a study of more than 700,000 patient records evaluated SABA inhaler usage, patterns of prescribing and rates of asthma-related hospitalizations.

Local treatment of lung cancer by the inhalation route is an emerging therapeutic area, particularly for early stages of the disease when the cancer is localized in the lung tissue. This article outlines manufacturing and formulation considerations for local treatment of lung cancer by dry powder inhaler and highlights three recent case studies.

The earliest reference to therapeutic dry powder inhalation may also be the earliest reference to “engineered particles,” dating from 1849, in London. An initial article looks at the history of dry powder inhalers, including devices and formulations, and discusses considerations for future DPIs. Then an interview takes a new look at current challenges and opportunities for DPIs.

AAFA has launched the Health Equity Advancement and Leadership (HEAL) program to address findings from its 2020 report about asthma disparities in America. Each year, the HEAL Innovation program will award funding and resources to four local, pilot, community-based asthma programs tailored to at-risk populations most impacted by asthma and will focus on needs of adults and teens.

CFD modeling for product development requires knowledge of the capabilities of state-of-the-art software and the adoption of a well-controlled simulation workflow. This article will review previous work in this area, illuminating CFD capabilities and the processes and considerations required to create a trusted, useful, predictive simulation to support the product development process.

The four parts of a dry powder formulation (the formulation, excipient, composition and processing) must be thoroughly understood in order to develop and optimize adhesive mixtures for inhalation. In addition, their interactions can be highly complex. This article gives examples and discusses the complex interaction between the formulation and the device.

This article discusses CFD simulations of nasal spray transport and use of CFD modeling to design nasal spray devices and analyze spray delivery performance. In silico testing using CFD, guided with in vitro measurements, is a potentially valuable approach that can reduce time and costs of evaluating nasal spray delivery performance under variable usage conditions in realistic nasal airway models.

HEI undertook the Global Burden of Disease from Major Air Pollution Sources (GBD-MAPS) project to determine which air pollution sources or fuels contribute most to outdoor PM_2.5 concentrations and their associated health burden. The study provides the first comprehensive estimates at global, regional and national levels, which can help inform policy.

Dry powder inhalation (DPI) products basically consist of a powder formulation and a device. The formulation, which contains active pharmaceutical ingredient(s) (APIs) micronized to inhalable particle size and a few excipients may, at first glance, appear simple. However, a large number of factors are critical to the performance of dry powder formulations for inhalation. Furthermore, many of these interact in complex ways.

Greater associations between risk of mortality and long-term exposures to relatively low concentrations of fine particulate matter (PM_2.5) have been reported. Recognizing “more stringent air quality standards and guidelines will likely be considered,” The Health Effects Institute has funded three studies—in the United States, Europe and Canada—“to explore health effects from air pollution exposure at levels below government recommended standards."

Considering flow conditions in the DPI test system has led to understanding more about why experts have improved the pharmacopeial protocol over time. Still, there are aspects of the fundamentals that are not yet clarified but worth understanding and accommodating in the protocols. The authors believe these include specifications for the solenoid valve, the effect of the pre-separator, control of the flow rate and measurement of the flow rate.

A large gap exists between the relatively straightforward robust methods in the pharmacopeias, developed primarily for product release, and the more elaborate approaches to assist in understanding how inhalers are likely to perform in the hands of the patient or caregiver. The authors propose that there is a middle way forward and believe it is possible to retain robustness in methodologies, while achieving significant gains in clinical realism.

Researchers from Tulane University School of Medicine analyzed operating costs of a partnership between school-based health centers (SBHCs) and a local allergist providing asthma care for students. Results showed the program was sustainable and cost-neutral and did not rely on grant funding.

A community-based program to help manage children’s asthma, developed with and successfully piloted in four Bronx schools, is expanding in up to 40 schools across the Bronx. The five-year “Asthma-PASS” study is supported by a $4.2 million grant from the United States National Institutes of Health (NIH).

This article provides an overview of the considerations for the formulation development of inhaled biologics and the various excipients that are routinely investigated for use in dry powder formulations of biologics intended for oral inhalation, with particular emphasis on protein stabilization. Carbohydrates, including simple sugars, complex sugars and sugar alcohols; amino acids and surfactants are discussed.

This article describes legislative and commercial drivers for propellant change and potential propellants, as well as the Respitab® technology platform, which provides a novel approach to formulation and manufacturing of lower global warning potential (GWP) pMDIs. Studies are presented and manufacturing and considerations for its use are discussed.