By David Vaczek
As formats that offer therapeutic advantages and support compliance, thin films and transdermal systems are expanding into new applications and drug categories.
The oral thin-film market (OTF) is growing with the launch of drug-loaded over-the-counter (OTC) formats in new categories, such as smoking cessation, and the development of prescription drugs in OTF format.
Formulators are also focusing on developing the next generation of dissolvable films, drawing on the inherent flexibility of film technology, reports ARx LLC (Glen Rock, PA), a subsidiary of Adhesives Research.
Film formats support controlled dissolution rates and rates of absorption, for applications such as topical, sublingual, implantables, and
“Most of the filings we are seeing today are for immediate release forms. The next generation of dissolvable film technology will be sustained release, and multidrug combination products,” says Martha Sloboda, business manager, ARx.
A pharmaceutical company is planning to launch the first oral film analgesic in sustained release version for a new indication of a reference drug.
ARx will manufacture the infused film; the customer will package it in a unitized pouch. “This is a new format of a well-characterized molecule that has only been available in tablet form,”
FDA approval of a 505 (b2) filing is expected on the product by November, after the agency completes a pre-approval inspection and authorizes ARx for the manufacturing.
Films are also advancing for localized topical delivery applications, providing benefits in precise systemic dosing, portability, and leakage
Film formats, for example, can be applied like adhesive bandages and dissolve when water or other agents are applied to create a reaction.
Sloboda says an ARx client is planning a first quarter 2010 launch of a prescription dermatological product in dissolvable film form that ARx will manufacturer.
Multizone coating or multilayer drug construction where two or more layers of API-loaded films are combined in one format is another emerging area.
“Multizone coating has existed for decades in other industries, such as in batteries that incorporate different materials that react with one another when charged. The concept is very well understood, very well characterized, and very precise because it comes out of the electronics arena.
“In the area of drug delivery, it becomes an enabling technology by providing the benefit of layering APIs that would otherwise be incompatible. With this approach, the APIs work together synergistically, once ingested,” Sloboda says.
“We have had success with this at the manufacturing scale, so we know it is scalable, and we are currently looking at a number of different therapeutic areas,” she adds.
Labtec (Lagenfeld, Germany), the wholly owned affiliate of tesa AG (Hamburg), has licensed Ondansetron RapidFilm to pharmaceutical companies in Europe, Korea, Turkey, and China. The oral thin film delivers the nausea and vomiting drug ondansetron, a generic of the Zofran Zydis Lingual Oral Dissolvable Tablet.
With Ondansetron RapidFilm, “Labtec has developed a product using its proprietary RapidFilm technology that is likely to be the first prescription oral thin film ever to reach the market,” says Gunnar van der Geest, corporate communications manager, tesa. “Companies are awaiting first regulatory approvals within this year.”
RapidFilm is a nonmucoadhesive fast-dissolving oral-dosage form based on a water soluble polymer. The film disintegrates within seconds in contact with saliva and promotes gastrointestinal absorption comparable to
immediate-release oral-solid dose forms, van der Geest says.
Donepezil RapidFilm, a generic of Aricept, for treatment of Alzheimer’s disease, is under development and has passed bioequivalency studies.
“All medications with single doses of up to 30 mg, the present capacity limit that allows the film to disintegrate rapidly, are candidates for RapidFilm formulations,” van der Geest says.
Tesa moved into the pharmaceutical development market with the acquisition of Labtec last year. The merger combines tesa’s converting expertise in self-adhesive films and coating technology, with Labtec’s competency as a contract developer of pharmaceuticals. The company focuses on coated therapy solutions in thin-film and transdermal-patch formats.
Labtec has developed patches for postmenopausal symptoms, decongestant delivery, and for nail disease treatments. Fentanyl TDS, a matrix patch for the treatment of chronic pain and a generic to J&J’s Durogesic, “was a major success which evolved to be a market leader in Germany today (under license to ratiopharm GmbH),” van der Geest says.
“The recent development and licensing focus is on Sufentanil TDS, a patch based on Labtec’s proprietary matrix technology. Sufentanil is the most potent substance in its class and has a superior pharmacokinetic profile, making it an ideal candidate for the next generation patch for treatment of moderate to severe chronic pain,” van der Geest says.
“We see CNS-active drugs such as for the treatment of Alzheimer’s and Parkinson’s diseases, together with new developments for pain therapies, as market–driving indications for the next several years,” he says.
J-PAC LLC (Somersworth, NH) has expanded its manufacturing capabilities with the addition of a Thin Film Converting and Platen Sealing System from sister company Doyen Medipharm (Lakeland, FL; Wymondham, UK). For converting edible film into oral strips, the line operates up to four lanes and slits and cuts hundreds of strips per minute. Strips are platen-sealed into four-side-sealed (4SS) single-dose sachets.
Besides converting and packaging systems that individually package strips into foil pouches in up to eight-lane configurations, Doyen makes machines for strip packaging in cassettes. Bulk rolls can be slit in up to 24 lanes, stacked, and cut to length and stacked for delivering up to 24 strips per package, says Mike Taylor, director of U.S. sales, western regional office, J-PAC/Doyen Medipharm (Oakland, CA).
“We have noticed a rise in oral-strip machine inquiries in the past months, both with cassette packaging and single-dose sachet modules. Currently, there are few OTC strips on the market. However, we know that oral strip formulations against nausea have reached registration stage with FDA this year and that there are more formulations in the pipeline,” Taylor says.
For lower production requirements for wound care manufacturing, Doyen has introduced the entry-level 4DS Wound Dressing Converting Machine.
The 4DS supports flexible tooling for handling different products and dressings including island, matrix, and IV-style dressings. The unit features four die stations, with a series of mandrels for unwinding and rewinding of roll stock.
“[Besides wound care dressings] the 4DS has the potential for a wider range of multi-layer medical products. We have had interest from companies involved in diagnostics and ostomy who see the benefit in a flexible converting machine for die-cutting and laminating their products,” says Taylor.
Doyen’s higher-end DMS wound care dressing converting machine handles larger reels and can be customized to manufacture more complex products, using more than four die stations. The unit includes space to incorporate printing, visual inspection, and sophisticated reject systems, Taylor says.
“The same processing principles as in the DMS are applied in our TMS transdermal patch converting systems which also support multi-lane operations,” he adds.
The 4DS supports multiple sets of tooling set in the same machine base, “a distinct advantage for clients that want to produce smaller batches of a range of products,” Taylor says.
Finished product would be manually transferred from the standalone 4DS to a packaging machine. For DMS installations, Doyen rotary 4SS or platen-sealing packaging machines are often integrated. Doyen this year launched a broader range of options for medical device packaging with the MT150 and MT250 thermoformers.
Forming and sealing options for the top and bottom webs and multiple cutting options can be customized to customer requirements, Martin Beriswill, Doyen’s vice president of engineering and product development, reported at EastPack.
“Many medical devices are not suited for effective 4SS packaging. With the MT series, Doyen now provides packaging machines for flat as well as three-dimensional products to the highest standard,” Beriswill said. ■