The next step in drug delivery

By Lynda Charters

Reviewed by Sean Ianchulev, MD, MPH

San Francisco-A new topical micro-droplet delivery system (Micro-Droplet Piezoelectric Ejection System, Corinthian Ophthalmic) may be an improvement first step over the eye dropper to deliver topical medications.

Such a drug-delivery system might standardize instillation of drugs and prevent over-treatment and improper instillation, thus aiding patient compliance, according to Sean Ianchulev, MD, MPH, clinical associate professor, University of California, San Francisco.

Dr. Ianchulev identified some major challenges encountered with the conventional eye dropper, such as overflow, inability to deliver inside the eye, and uneven distribution to the ocular surface. Even when instilled correctly into the eye, the vast majority of a single eye drop is lost within the first 15 to 30 seconds after instillation, either by lid overflow or via the nasolacrimal duct system. In stark contrast with most other pharmacologic delivery methods (e.g., pills, intravenous), there is little control on what amount of drug is actually delivered to the target tissue (i.e., the ocular surface) when a physician prescribes a topical formulation.

To overcome this problem, investigators have attempted to deliver medications by spraying the drug onto the eye, but initial efforts with such systems as atomizer sprays have failed due to inability to control droplet size and flow dynamics for consistent and predictable administration. Major problems related to the physics of droplet ejection, such as dispersion, droplet evaporation, drag, and non-collimated flow turbulence, have held back such new approaches until recently.

“There is a reason why we have been using the conventional eye dropper for more than 100 years, even though we are well aware of its deficiencies,” Dr. Ianchulev said.

A different approach

The micro-droplet piezoelectric ejection system may overcome these obstacles. The device, he explained, provides collimated flow in a manner similar to ink-jet printers.

“This facilitates depositing of the drug on the ocular surface and the result differs markedly from eye dropper instillation or spray,” Dr. Ianchulev said.

The delivery is based on the piezoelectric fluid ejection system, which monitors every application of a drug.

“Using sophisticated technology, the system is able to control the dosing and ejection of micro-droplets to enable direct application on the ocular surface,” he said. “It can be used across a platform of topical medications. Glaucoma, antibiotic, and mydriatic drops have been successfully sprayed using this delivery system.”

The technology has a light-emitting-diode optical targeting system that eliminates the need for the patient to tilt his or her head and delivers the spray within less than 30 to 40 ms, which is faster than the blink reflex.

Clinical assessment

A clinical study of the delivery system was performed to compare the dilating effect of a topical medication (2.5% phenylephrine and 1% tropicamide) delivered via the micro-droplet ejection device and an eye dropper. The study included 102 patients; one eye of each patient served as the control for which an eye dropper delivered the drug and the delivery system was used to deliver the drug to the fellow eye. The patients were randomly assigned to one of three study arms in which 34 patients received a 1.5-µl dose, 33 patients received 6 µl, and 35 patients two doses of 3 µl each.

The pupils were monitored by digital pupillometry at 10, 20, and 60 minutes following dosing.

“The results showed that the micro-droplet ejection system provided similar dilation and pharmacodynamics effect to that achieved to the drug instilled using the eye dropper-even though the spray administered one tenth of the volume of the eye drop,” Dr. Ianchulev said. “This is important because we can reduce ocular surface exposure to preservatives and for some drugs, such as beta blockers, systemic side effects can be avoided. The results made us very confident about investigating other drugs.”

When a glaucoma drug was tested in a similar manner in a canine model, the investigators achieved the same efficacy curves to those achieved with eyedropper instillation, he noted. The advantage of the ejection system is that a much lower volume of drug can be ejected onto the ocular surface to achieve the same effect as that using eye drops.

“The delivery system provided minimally dispersive targeted delivery to the eye and had a good safety and tolerability profile for delivery of most ocular medications,” Dr. Ianchulev concluded. “In addition, the system was clinically equivalent to delivery by an eye dropper based on the achieved dilation at lower doses. The ocular surface was exposed to less preservatives. The system will be validated further in equivalence studies of glaucoma drugs that will include multi-dose, preservative-free delivery.”OT

FYI

Sean Ianchulev, MD, MPH

E-mail: tianchul@yahoo.com

Dr. Ianchulev is a scientific advisor and member of the board of directors for Corinthian Ophthalmic. This article was adapted from Dr. Ianchulev’s presentation at the 2012 meeting of the American Academy of Ophthalmology.