The outlook is increasingly promising for products that deliver medicines to and through the respiratory system.
Since the mid-twentieth century, with the growth of high-technology medical engineering, pulmonary drug delivery has grown from a seed concept to a multi-billion dollar industry. In 2001, sales of products using pulmonary delivery systems reached $8 billion and some industry sources project this market to grow to $15bn by 2006. 1
After 50 years of development, metered dose inhalers (MDIs) that deliver drugs are an established market serving millions of patients worldwide. Nebulisers have held their niche position and new technologies have enabled portable versions that are gaining a foothold for various applications. Dry powder inhalers (DPI) are becoming increasingly important, with four DPI systems approved for asthma medications and 40 more DPI systems either in development or under regulatory review.
The first pulmonary system to deliver a large molecule drug to treat a systemic disease - insulin for diabetes - is in the late stages of development, with a DPI product called Exubera filed in Europe and in the USA by Pfizer Inc and the Sanofi-Aventis Group. Inhalable systems for proteins, peptides, oligonucleotides, and numerous small molecules for local and systemic effect are in earlier development phases.
Accelerating technical advances over the past decade are enabling new and different, as well as cheaper and better, approaches to pulmonary drug delivery. These include ongoing improvements to MDIs and nebuliser systems, and continued improvements in all aspects of DPI systems. Pulmonary drug delivery is coming of age as a way to extend the lifecycle of existing products, improve upon drugs on the market, and deliver new chemical entities in more efficient and effective ways.
DPIs offer the greatest potential of any approach to pulmonary delivery. When engineered properly, dry powders can meet the criteria for success while delivering a wide range of molecules - from traditional asthma drugs and small molecule antibiotics, to peptides, proteins, antibodies and oligonucleotides. In particular, delivering biologicals to the deep lung for systemic diseases offers the most promising inhaleable platform for successful systemic administration of biologicals.
The market is on the brink of realising pulmonary delivery of large molecules for chronic systemic diseases with inhaled insulin under regulatory review in both the EU and the USA. It looks likely that the gateway will be opened for products for chronic administration of systemic peptides.
Continued advances in the technologies used to manufacture drug powders for inhalation, especially improvements in particle engineering and formulation methodologies for controlling particle size, are enabling faster, cheaper and better approaches to delivery of drugs to and through the lungs, including biologicals. Thus the longer-range future of DPIs includes portable, non-invasive delivery of large molecules for systemic conditions, both as product extensions for drugs now given by injection and from the beginning of the development process for new chemicals.
Pharmaceutical companies and drug delivery companies are also focused on developing pulmonary delivery systems to treat local lung diseases, and to deliver drugs for conditions where fast onset is desirable, such as pain relief, allergic reactions and sexual dysfunction. Many new agents are under investigation for pulmonary delivery, both for targeted lung and systemic delivery. These include growth hormone alpha-1 antitrypsin interferons and parathyroid hormone and other peptides. Inhalation delivery methods may also be applied to gene therapy via tissue targeting and organ targeting, as well as to vaccines, especially for respiratory diseases. Additional concepts include a DPI pulmonary version of EPO-Fc conjugate, and DPI delivery of antibiotics for tuberculosis.
With maturing pharmaceutical marketing, a focus on better drug delivery has become an important and growing aspect of pharmaceutical product development and franchise management. Drug developers increasingly recognise the opportunities presented by integrating new delivery methods into product development to extend product lifecycles and to increase sales by enabling better performing drugs and improved patient compliance.
The 1990s were a wild decade for the development of new technologies for pulmonary delivery. As products advance in the early years of the twenty-first century, pulmonary delivery will be an increasingly important part of the growing emphasis on state-of-the-art drug delivery as part of optimising product characteristics in an increasingly competitive pharmaceutical development environment.
1 Minter, Brian, Opportunities in Drug Delivery: Identifying hot technologies, companies and markets, Urch Publishing Ltd, 2003.
DPIs offer the greatest potential of any approach to pulmonary delivery
Nektar Therapeutics (formerly Inhale Therapeutic Systems, Shearwater and Bradford Particle Design) is a pioneer in advanced drug delivery technologies that enable highly differentiated products.