Increased drug product complexity, the rise of biopharmaceuticals, novel therapeutic technologies, bioavailability challenges and the demand for the demonstration of strong drug performance are all factors driving unprecedented drug-delivery technology innovation. In addition, cost pressures in the healthcare system and patients’ busy schedules are requiring increasing levels of self-administration.
These demands call for advanced drug-delivery technologies that improve drug efficacy and safety by controlling the time, rate and place of drug release in the body. In addition, pharmaceutical companies are seeking to improve patient compliance, extend patent protection and achieve competitive differentiation.
Reinforcing the importance of advancing drug-delivery technologies, in the United States alone, more than 50 percent of prescribed medications are taken incorrectly or not at all. It is sobering that the incorrect use of medications has been linked to up to 125,000 deaths annually, and the IMS Institute for Healthcare Informatics reported that more than $200 billion might be saved each year by increasing patient adherence.
This report explores some of the fascinating advancements in drug-delivery technologies, including oral dosage form innovation, biopharmaceutical drug delivery, smart drugs and targeted drug release.
ORAL DOSAGE FORM INNOVATION
Oral drug delivery remains patients’ preferred method of drug delivery. Compared to injectables, oral dosage forms are much easier and more comfortable for patients to self-administer. This ease and comfort increases patients’ adherence levels. Additionally, solid dosage forms are often less expensive to manufacture.
However, many pharmacology advancements in recent decades have been large-molecule drugs or other complex therapeutics that are extremely difficult to manufacture in solid dosage forms. Even many small-molecule drugs are difficult to deliver effectively. As a result, approximately 70 percent of molecules exhibit poor solubility, which could limit bioavailability.
One new oral dose approach is dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods for oral solid dosage products. This technology uses drop-on-demand printing technology for the automated and controlled deposition of solution-, melt- or suspension-based formulations onto edible substrates. The advantages of drop-on-demand technology include the highly reproducible production of small droplets, adjustable drop sizing, high placement accuracy and flexible adaptability for different formulations. These features enable the production of individualized dosing - even for low-dose and high-potency drugs - and suggest a promising manufacturing technology as personalized medicines continue to advance.
Another exciting and promising oral delivery technology is being achieved by molecular farming. Molecular farming is the use of plants for the production of scalable and safe, high-value recombinant proteins for use in pharmaceuticals. Several approaches are being explored utilizing proteins produced by molecular farming. However, one of the most promising approaches is the use of edible plant organs that express biopharmaceuticals for direct oral delivery. This technology holds the promise of eliminating many costly aspects of biopharmaceutical production, including expensive processing, purification, cold chain storage and transportation costs.
TRENDS IN BIOPHARMA DRUG DELIVERY
While nearly all biopharmaceuticals to date have been injectables, much progress is being made in the development of drug delivery that is less invasive and easier to self-administer. New biopharmaceutical drug-delivery formats in active development include oral, inhaled and micro-needle administered dosage forms.
As with chemically synthesized small-molecule drugs, the oral delivery of biopharmaceuticals is generally viewed as the most desired route of administration. There are, however, many obstacles to delivering biologics by non-injection methods, often because of temperature and other sensitivities of proteins. Delivery methods including lipid-based formulations within softgels and next-generation orally disintegrating tablet (ODT) formulations, as well as inhaled, transdermal and ocular delivery, are showing promise.
Advanced particle engineering is facilitating the oral delivery of biologics to the lungs. For example, in 2014, the FDA approved Afrezza, an inhaled form of insulin that catapulted inhalation devices to the front and center of drug-delivery innovation.
While the non-injectable delivery of biologics is actively being pursued, many biologics, for the near future, simply must be injected. The need to reduce healthcare costs and patients’ busy schedules dictate that self-administration will rise as the use of biologics increases. Packaging and delivery solutions, including prefilled syringe systems, wearable pumps, auto-injectors and wearable patch injectors, are helping to solve some of the administration constraints that have inhibited the use of biologics in the past.
Oral delivery of biopharmaceuticals remains a very sought-after goal. Novo Nordisk, in pursuit of advancing the effort, formed a research collaboration with Professor Robert Langer’s laboratory at MIT to develop drug-delivery devices for the oral delivery of peptides. The goal of this work is to overcome challenges in developing and manufacturing peptide delivery vehicles that meet both efficacy and reliability objectives. Among the many challenges that need to be overcome are premature degradation in the body, poor peptide transport over epithelial barriers and variability of absorption. In addition to these drug performance considerations, technologies that facilitate manufacturing cost-effectively and at the needed scale are leading challenges.