Comfort In Parenteral Delivery

Advanced parenteral delivery solutions are affording product differentiation and therapeutic benefits across a range of therapies.

In needle-based injection, cartridge-based pens and prefilled syringes loaded into disposable auto injector devices offer features that support easier self administration by patients.

Antares Pharma Vibex injectors feature adjustable needle penetration and adjust to alter injection speed for viscous product.

Used for daily therapies and those less frequently administered, these devices require fewer steps and make the injection process less difficult and safer. As more easily used delivery systems, they promote regimen adherence among self-treating patients.

In transdermal delivery through patch and gel technologies, the side effects of orally administered drugs that often cause noncompliance are reduced or avoided.

Needle-free injection therapy systems—promising for applications including pediatric vaccines and self-administered injections for chronic conditions—also address patient adherence, as patients facing daily injection don’t also have to face a needle.

Genentech (www.gene.com) provides unique features that support patient dosing with the Nutropin AQ NuSpin, a prefilled multi-dose injection pen, for administration of Nutropin [somatropin (rDNA origin) injection], a recombinant growth hormone.
After the launch of Nutropin AQ NuSpin in 2009 for the adult human growth hormone market, Genentech announced availability of the system in 2010 for the pediatric market.

Advanced features of the device improve patient ease-of-use compared to Genentech’s earlier AQ Nutropin pen, a reusable device that requires patients to load in the cartridges. Delivered prefilled with the cartridge, the Nutropin NuSpin is disposed of after use. The device comes prefilled with 5-, 10-, and 20-mg cartridges, denoted by different device colors.

VISUAL CUES

The patient sets the dose using a unique “spinning” dose knob that spins as the dose is administered. The selected dose amount is shown in a small window, says Donna French, senior director, device development, Genentech.

“The spinning knob provides a strong visual indicator. The patient can be assured when the injection starts, when it is happening, and when it is finished. (In addition), if the patient accidentally over turns the knob in setting the dose, it can be turned back and forward with ease to select the correct dose,” French says.

After the needle is inserted into the skin, the drug is automatically delivered after the patient moves a sliding dose activator on the side of the pen.

“The drug is pushed through the needle into the subcutaneous space automatically. With Nutropin NuSpin, we have the only
disposable pen on the market with automated drug delivery. Patient feedback has been excellent,” French says.

Genentech has partnered with two contract manufacturing organization (CMOs) to produce a market ready product, says Gerald Llorach, head of combination products, CMOs.

One makes the device; the second fills the cartridges and performs final assembly for delivery to a Genentech distribution center.
Antares Pharma (www.antarespharma.com) offers technology platforms for self-injection of drug products as well as for transdermal delivery. Automatic injecting devices such as Antares’s Vibex pressure-assisted auto injector platform leverage technology first developed for the company’s Medi-Jector needle-free delivery system.

Concepts employed in the Medi-Jector are applied to Antares’s mini-needle auto injectors for rapid and confortable self-injection.
“We have one of the most powerful spring-generated injection technologies available. We have applied the Medi-Jector technology to auto injectors for subcutaneous and intramuscular delivery in devices that have to withstand the pressures generated during injection with this technology,” says Paul Wotton, PhD, Antares president and CEO.

PAIN Avoidance

“As a company with a lot of history with this type of injection technology, our mission is to make it easier for patients to self-inject at home without fear of pain,” Wotton says.

In addition to out-licensing its technology platforms, Antares is developing its own pharmaceutical products and partners with pharmaceutical companies to develop and commercialize novel parenteral drug/device combination products using its drug delivery systems.

“There is a huge need for systems that help companies differentiate product in the market while promoting patient safety, enhanced comfort, and adherence. Of the $50 billion U.S. market for biological products, we estimate that self-administered products account for over half the total,” Wotton says.

“(Also) biological drugs tend to present injection challenges due to the viscosity of the solutions. Injection devices designed to improve patient comfort and compliance will be crucial to differentiating biological products, particularly biosimilar versions of marketed biologics,” he adds.

In needle-free delivery using Antares’s Vision technology, the device releases a thin stream of the drug that permeates through the outer layer of the skin into the tissue undernealth. The system is used in Teva Pharmaceuticals’ Tjet device for injection of Tev-Tropin human growth hormone (hgh). In Europe, Ferring Pharmaceuticals provides Zomacton hgh in
Antares Zomajet 2 Vision and Zomajet Vision X devices.

Last month Antares announced the dosing of the first patient in a clinical study evaluating Vibex MTX, being developed for the treatment of rheumatoid arthritis. Vibex MTX is Antares’s proprietary methotrexate injection system for patient self administration of the drug. The subcutaneous delivery system offers an alternative to conventional needle and syringe administration by a caregiver, and to oral dosing.

“Many patients are not able to tolerate methotrexate when given orally. Also, injection delivery minimizes dosing variability. The dosing is not easily reproducible when taken orally especially at higher doses,” Wotton says.

“Methotrexate for injection is increasing used in this country for rheumatoid arthritis patients. Our research has shown that given a practical means of enabling subcutaneous administration, rheumatologists would offer the option to many patients who either don’t tolerate or adequately absorb methotrexate,” he adds.

Delivered to the patient as a ready to use unit, Vibex MTX incorporates the drug in a prefilled syringe and needle. Antares’s partner Uman Pharma (Montreal) formulates and packages the drug into syringes for final assembly into the device.

RAPID INJECTION

In use, the patient flips off a safety cover, removes the needle cap, and pushes the device against the skin. When pushed against the skin, a collar retracts to expose the needle to a shallow depth, triggering delivery.
“It’s a comfortable procedure. The collar pressure distracts the patient a bit so you don’t feel the needle. We are trying to make injection as easy for the patient as taking a pill, while also improving therapeutic performance,” Wotton says.

Wotton notes that auto injection with typical injectors takes seven to ten seconds. “The whole procedure using Vibex takes three seconds and the injection of a ½-ml or 1-ml dose is accomplished in a second or less,” he says.

Vibex’s coil-spring system is also paired with the allergy emergency drug epinephrine in a disposable, single use injection developed with Teva Pharma as a generic version of the EpiPen.

In transdermal drug delivery, Antares is developing Anturol for treatment of over active bladder. Based on the company’s Advanced Transdermal Delivery (ADT) Gel technology, Anturol is formulated as a version of oxybutynin for optimizing the drug delivery in a non-patch transdermal form. Antares filed an NDA for Anturol in December 2010.

“It has been well recognized that transdermal delivery of drugs is a safe and effective way of delivering certain drugs that undergo first pass gastric and hepatic metabolism. We’re hoping for approval in the next 12 months,” Wotton says.

The ADT Gel technology is also used to deliver Azur Pharma’s FDA-approved Elestrin menopause drug, in NestraGel, a Phase II contraceptive being developed with the Population Council, and in BioSante Pharma’s Phase III female sexual dysfunction drug LibiGel.