Pulmonary Drug Delivery: The Emerging Paradigm in Drug Delivery

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Pulmonary Drug Delivery Overview

The inhalation route is one of the oldest methods of drug delivery, dating back at least 4,000 years when ancient people smoked various herbs to alleviate symptoms of asthma.  This practice has evolved into modern respiratory therapy, which includes the use of drug delivery devices like pressurized metered-dose inhalers, dry powder inhalers, and nebulizers.

Pressurized metered dose inhalers (pMDIs) utilize a drug suspended in a propellant (typically a hydrofluoroalkane).  As the device is actuated, the metering valve fills with a measured volume of propellant-drug mixture within the pressurized chamber, which expands upon release into the atmosphere, propelling a precisely-measured, aerosolized dose of drug.

Dry powder inhalers (DPI) are devices where premeasured powder dose is held in a sealed blister or a capsule that is manually loaded into the device.  The device is actuated to open the blister or puncture the capsule, and drug is aerosolized and inhaled upon inspiration.

Lack of patient training can often be a challenge with pMDIs and DPIs, since coordination of inspiration and actuation of the device is necessary to deliver the proper dose.  This can be a problem for patients with limited respiratory function, or for drugs with a narrow therapeutic window.  These limitations can be overcome using the third type of delivery device, the nebulizer.  Nebulizers use a piezoelectric vibrating membrane or high velocity fluid jet to aerosolize a continuous stream of drug.  Nebulizers are sometimes limited in their effectiveness because of their relative lack of portability, but they are ideal for a clinical setting and for patients with limited pulmonary function.

The Benefits of Inhalable Therapeutics

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Depending on the indication, there are several benefits to aerosol formulations compared to more traditional dosage forms (e.g. oral, parenteral).  For example, in diseases like asthma or chronic obstructive pulmonary disease, local delivery of the drug to the disease site can often minimize systemic side effects and lead to rapid action, for example, in the case of abortive asthma therapy.  For systemically acting drugs (e.g. the recently-approved inhalable insulin product Afreeza(tm)), the lungs provide a large alveolar surface area suitable for systemic absorption (70-140 square meters in an adult human).  Additionally, the pulmonary route of delivery has the added benefit of avoiding the first-pass hepatic metabolism associated with oral drug delivery.

A Growing Market

There are many inhalable drug products currently available and the market is rapidly growing.  One of the top selling drugs in the world, Advair(tm), is an inhalable drug.  Advair(tm) is a fluticasone-salmeterol formulation sold by GlaxoSmithKline for the treatment of asthma and chronic obstructive pulmonary disease.    It was the eighth highest-grossing pharmaceutical product in 2014, with global sales of $6.7 billion USD.  According to the FDA Orange Book - a compilation of all approved drug products, the number of inhalational drug products has increased from an average of 1.5 products per year from 1938-1982 to an average of 10.7 products per year from 2010 to 2017.  Overall, the aerosol drug generic market is expected to reach $35.5 billion USD by 2023.  This growing market will demand precise methods of testing inhalational products in both preclinical and clinical studies.

Challenges for the Future

Preclinical inhalation studies present unique technical challenges.  The most common laboratory method of pulmonary formulation testing is intratracheal instillation, which requires the use of a special syringe to deliver a drug solution or powder. This device must be precisely placed into the test animal’s trachea, which is tedious and challenging for small animals like rodents and often leads to variability in the delivered dose.  This can lead to imprecise data and may necessitate repeated studies to meet data integrity standards and to overcome regulatory hurdles.  This challenge can be overcome with new technologies designed to deliver precise and repeatable doses of inhalable drugs. 

Technology for the Future of Drug Delivery

Learn more about how PneumoDose can help your company generate high-quality inhalational data.

References

  1. Gandevia B. “Historical review of the use of parasympatholytic agents in the treatment of respiratory disorders.”  Postgrad Med J.  1975(51):13-20.
  2. https://www.afrezza.com/
  3. Groneberg DA, et al.  “Fundamentals of pulmonary drug delivery.”  Resp Med.  2003(97):382-87.http://www.pmlive.com/top_pharma_list/Top_50_pharmaceutical_products_by_global_sales
  4. https://www.accessdata.fda.gov/scripts/cder/ob/
  5. Inhalation and nasal Spray Generic Drugs Market Expected to Reach US$35.5 bn Globally by 2023.
  6. Transparency Market Research.  23 February 2016.  
  7. Patil JS, Sarasija S. “Pulmonary drug delivery strategies: A concise, systematic review.”  Lung India 2012(29):44-49.