ACCORDING TO A RECENT REPORT by MarketResearch.com, the U.S. market for drug delivery-modified therapeutics-currently at $23 billion-is expected to grow to $76 billion by 2014. That works out to an 18 percent average growth rate per year for the next eight years.
The number of new chemical entities (NCEs) is a key market driver. "The number of NCEs being approved by the FDA has declined compared to 10 years ago, so when you don't have new drugs coming into the market, companies are going to leverage the existing data on already-approved drugs to make better drugs," says Padmanabh P. Bhatt, Ph.D., vice president, pharmaceutical sciences, Supernus Pharmaceuticals Inc. (Rockville, Md.). "Because if a drug is on the market, it is already known that it is efficacious and safe to a certain degree for the patient."
Medicines can be delivered to patients in a number of ways, including orally (with tablets or inhalants), injection, and via patches, but oral delivery with tablets stands out as the preferred method.
Oral delivery is the most desirable route of administration because we are all used to putting things in our mouth when we eat or drink. When a patient is asked to take a capsule to receive medicine, it's very easy to administer.
Tablets and capsules are not just easier for the patient to take, but they are also easier to manufacture. To make an injectable, the formulation has to be sterile. The sterilization process makes the manufacturing process more expensive as opposed to the oral formulations, which do not have to be sterilized. "Our mouth and gastrointestinal tract are more accommodating to ingested items with microorganisms on them," says Bhatt. "If a non-sterile injection formulation enters the body, there could be a life-and-death situation for the patient."
Oral formulations, when administered correctly, have a greater chance of delivering medicine safely to treat diseases that affect targeted areas of the gastrointestinal tract.
Anand Baichwal, Ph.D., chief scientific officer and senior vice president of licensing for Penwest Pharmaceuticals Co. (Danbury, Conn.), notes that the optimal delivery type is directly linked to knowing what disease you intend to treat. "How you deliver depends on whether you want to treat acute conditions or chronic conditions," he says. "Then you decide what drug is needed to treat the disease, and then figure out how to deliver it to maximize efficacy and reduce side effects."
Alternatively, Baichwal says that another way to approach the delivery decision is by starting with the drug delivery technology and then figuring out what diseases it could be applicable to.
A tablet can maximize efficacy and have minimal side effects via targeted delivery. What types of delivery are available? Targeted delivery, chronotherapy, and pulsatile delivery are three currently acceptable and evolving technologies.
Drugs designed for targeted delivery will deliver the drug to a particular site in the gastrointestinal tract, not before it reaches this site. "For example, some disease states require that you deliver the drug in the colonic region, but the drug is not needed in the part above this region in the gastrointestinal tract," explains Bhatt. "Then you would design a tablet or capsule that would release medicine in the colon, the targeted area."
Chronotherapy allows you to synchronize medication with the biological rhythms of disease activity (Figure 1.). With this delivery, the oral dosage waits for an event in the disease activity before it releases. Dr. Bhatt gives hypertension as an example. "It was found that the blood pressure and chance of myocardial infarction was greatest just before awakening in the morning. To reduce the chance of a heart attack in patients that are hypertensive, you can administer a tablet with chronotherapy delivery that releases the drug in the body during the night, but the peak effect of the drug is in the morning."
Pulsatile delivery, according to Baichwal, is delivered in "pulses," so the medicine can be released into the body in pulses when it is needed. This controlled-release formulation can allow half of the dose to be delivered immediately-when you swallow the tablet-and the other half hours later when it reaches the desired region in the gastrointestinal tract.
"If you want to target the colon, you can have a formulation coated with a polymer that will not dissolve until it reaches a certain pH level," explains Bhatt. "The pH in the colon is higher (6.5 to 7) than areas above it in the gastrointestinal tract." As soon as it dissolves, the rest of the drug is released. The gastrointestinal tract has regions of differing pH levels.
So now your specialty pharmaceutical company has a delivery technology and knows what disease it wants to treat. How do you bring your product to market?
Drug delivery technology companies need to step up and create their own pipeline to experience the exponential growth mentioned in the beginning of this article. "The real growth of the company will come from developing their own pipeline and moving a drug towards commercialization," says Bhatt. If you do not have all of the tools in-house for development through product launch to the public, teaming up with another specialty pharmaceutical company or marketing entity could be beneficial.
"We partner primarily in formulation development," says Irwin C. Jacobs, Ph.D., director of RandD, for Particle and Coating Technologies Inc. (PCT; St. Louis, Mo.). "Many companies can perform analytical work, validation for potency and stability, as well as cleaning validation."
Penwest has four proprietary oral drug delivery systems, is capable of moving products through to FDA approval, and is also expanding through the licensing of compounds and technologies for a wider breadth of medicines. However, Penwest does not have a dedicated sales force. It is common for a delivery technology or development-focused specialty pharmaceutical company like Penwest to seek a partnership with a sales and marketing entity.
Other specialty pharmaceutical companies can benefit from a partnership with a delivery technology company as well. For example, Penwest entered into a venture with Endo Pharmaceuticals, which specializes in the pain area, to develop and move a pain drug through to FDA approval. "The partnership started in 1998, when we didn't have the clinical and regulatory capabilities," explains Baichwal.
KEEPING THE PATIENT IN MIND
Even though the mouth and gastrointestinal tract can ingest microorganisms that may be on tablets, you still need to watch for current FDA standards for controlled release formulations to make sure that patients administer correctly.
Bhatt offers an example. "Suppose you give a drug four times a day," he explains. "You have all of this medicine in a once-aday tablet, and the FDA is worried because there have been instances where people have taken these medicines with alcohol. If a dose dumping is caused, this could lead to death." (For more information about this FDA stance and the agency's other recommendations for controlled release drugs, take a look at the FDA's "Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products-General Considerations," which can be found at
Safe administration is important, especially as drug delivery will become more patient-controlled. "As a result of the Internet and direct-to-consumer advertising, patients are becoming more informed about drugs and want to have more control. The ease of oral delivery puts tablets and capsules in a greater position compared to other drug delivery technologies," says Baichwal.
"Suppose you give a drug four times a day," Bhatt explains. "You have all of this medicine in a once-a-day tablet, and the FDA is worried because there have been instances where people have take these medicines with alcohol. If a dose dumping is caused, this could lead to death.... Controlled-release drugs will also become even more personalized. We're learning that one drug and one delivery doesn't suit everybody, so genomics and phenotyping are helping to determine the proper drugs and delivery."
Controlled-release drugs will also become even more personalized. "We're learning that one drug and one delivery doesn't suit everybody, so genomics and phenotyping are helping to determine the proper drugs and delivery," he continues.At the end of the day, you need to keep the patient in mind. Jacobs warns that the increased complexity of the tablet could translate to an increased price for the patient. Are all of these new bells and whistles for a timed-release product worth an increase in cost to the patient? Only time will te