Epilepsy: 3D Printing provides an Easier Pill to Swallow

Thomas West, Aprecia Pharmaceuticals, tells us how they are using 3D printing to revolutionize the way people take medicine.

Anyone who has had the responsibility of caring for a loved one with a chronic illness can appreciate how difficult it can be to administer medication. Small children or elderly patients may refuse to cooperate, or simply be unable to swallow tablets. Indeed, a child’s esophagus may be smaller than normal, or not yet sufficiently developed to swallow a pill, while elderly patients may suffer from dysphagia (difficulty or discomfort in swallowing, as a symptom of a disease). This ongoing struggle can lead to skipped or incomplete doses, both of which represent inadequate adherence – and possibly compromised treatment outcomes.

Some of these patients might be given liquid suspensions, but the bitter taste of most medications can only be partially masked this way. Foul tasting medicine can trigger a gag reflex and cause the medicine to be regurgitated. Worse still, a struggle to swallow medication can cause aspiration, which can in turn lead to pneumonia. Yet it’s essential that an accurate and consistent dose be administered to patients with chronic conditions if any type of control is to be achieved.

According to Thomas West, Project Director and Manager of Intellectual Property at Aprecia Pharmaceuticals, “Our goal is to use our unique formulation platform to make medicine easier to take. It’s about providing a new dosing option that can help segments or groups of patients that may have difficulty swallowing large tablets intact.” Those living with epilepsy are set to benefit from this goal.

Adherence in epilepsy

There are many medications, known as anticonvulsants, used to treat epilepsy. Most standard treatments are oral tablets or liquid suspensions. The dose is usually weight-based in children and often requires twice-daily administration. Failure to take a dose or taking an incorrect dose could lead to recurrence of symptoms, including tonic-clonic seizures, which are usually characterized by loss of consciousness, uncontrolled movements, and disorientation.

Since many anticonvulsants come in liquid form, inability to swallow pills shouldn’t be an issue. However, inaccurate doses are still common with oral suspensions. Inaccurately filling the syringe or measured cup can cause errors in dosing. Similarly, the patient failing to swallow the whole dose or leaving a residue in the syringe or container can cause under-dosing.

Failing to adhere to a patient’s therapy can have catastrophic consequences. Breakthrough seizures are the most likely result, potentially causing serious injury to the patient. Seizures of this severity almost always result in falls, which can in turn lead to broken bones, head trauma, or even death. But even if the patient doesn’t endure tonic-clonic seizures, they run the risk of further brain damage and loss of function. Clearly, controlling all seizure activity with medication is in the best interest of the patient.

The goal of any pharmacologic therapy is to provide a complete, measured dose based on the prescriber’s recommendation. Physicians use sophisticated diagnostic tools combined with knowledge of therapeutic benefits to prescribe a dose designed to control symptoms and improve quality of life. These benefits are undermined by inadequate compliance to prescription directions. Finding a way to administer the exact, complete dose of a medication according to the recommended schedule must be the common aim of all prescribers, caregivers, and patients.

How 3D technology can help

Specialty pharmaceutical company Aprecia using a unique three-dimensional printing technology platform called ZipDose® Technology. “This serves as the foundation of our orodispersible formulations of highly prescribed, high-dose medications,” says West. “What’s important to note here is our proprietary process stitches together multiple layers of powdered medication using an aqueous fluid to produce a porous, water-dispersible matrix that rapidly disintegrates with a sip of liquid.” This revolutionary use of technology will make it easier for those with difficulty swallowing pills to receive a complete dose of medication. It replaces liquid suspensions that may be inaccurately measured, with a swiftly dissolving formulation.

This is especially pertinent to patients who suffer from epilepsy because, according to West, the FDA recently approved Aprecia’s first product - SPRITAM® (Levetiracetam). This is a widely prescribed anticonvulsant used to treat patients with epilepsy and can be given in tablet form or intravenously in a hospital setting for acute treatment. However, with 3D technology, patients will now be able to take their dose with just one sip of water rather than having to swallow the tablets intact.

Three-dimensional technology allows for a higher concentration of active ingredient than other fast-melt technologies using soft compression or freeze drying because it doesn’t rely on pressure to stamp the drugs into a tablet or force them into a gelatin capsule. Nor does it require multiple components to function. Of course, the active ingredient is what provides the actual therapeutic benefits, but most tablets require additives. In many cases, a bulking agent must be added to make them large enough to be taken effectively. A binder is used to hold the ingredients together, and possibly a degradant to break it apart in the digestive tract. On top of this, a lubricant is necessary to release the pills from the press, and a coating may also be needed to improve the taste and make the tablets easier to swallow. None of this is necessary when 3-D technology is used.

Indeed, with 3D technology, instead of combining the active ingredient with the other compounds and pressing them into a hard pill form, an aqueous substance can be used as its ‘ink,’ along with other excipients, and the individual tablets can be printed out layer by layer. Because the layers of powder are bound microscopically with this aqueous element, they are highly water soluble and dissolve rapidly when introduced to liquid.

Orodispersible tablets, or Orally Disintegrating Tablets (ODT), have become an important therapeutic alternative for patients who have difficulty swallowing pills. They are designed to dissolve on the tongue within sixty seconds and then be swallowed. This is achieved using a variety of methods, including effervescence and loosely packing the ingredients. ODTs have also been used for drugs that require buccal absorption due to low gastrointestinal bioavailability. The use of 3D technology to create pills using mainly the active ingredient and an aqueous component takes orodispersible administration to a whole new level.

There are two key benefits to using 3D technology: higher dosage and faster disintegration. According to West, “ZipDose® Technology represents a departure from prior ‘fast melt’ technologies, which have generally been limited to products with much lower strengths.” Aprecia indicates that approximately 98% of the ODT dosage strengths approved for commercial sale in the US, including generics, are below 200 mg, and that 94% of the dosage strengths are below 50 mg.

West also highlights that, “We have formulated prototypes that have delivered more than 1000 mg of a drug in a fast melt dosage form that disperses in the mouth within seconds when taken with a sip of liquid.” This is critical for patients suffering from epilepsy who frequently take doses of 1000 to 3000 mg per day. Imagine having to take five to fifteen ODTs to get the required dose. That would be far less attractive than a liquid suspension or oral tablets.

3D printing: the drug manufacture method of the future?

When asked how Aprecia hopes to use 3D printing technology in the future, West says, “Our initial pipeline will apply ZipDose® Technology to other molecules in the CNS [central nervous system] therapeutic area, and we believe these product candidates will complement one another.  A similar approach could be taken in the future for ZipDose® formulations in other therapeutic areas, either by ourselves or through strategic partnerships.”

There are clearly many applications for this exciting new technology. Most importantly, it should bring relief to beleaguered caregivers who struggle to cope with administering medications to chronically ill patients requiring maintenance medications.