Pharmaceutical Commerce - March/April 2013 - (Page 30)

Manufacturing & Packaging Transdermal drug delivery looks for new frontiers continued from page 1 proteins and peptides, and this obstacle has led to efforts to develop physical or active methods of overcoming the skin barrier, including: • Microneedles—sharp microprojections, frequently in patch form • Iontophoresis—a weak, continuous electrical current • Electroporation—short, high-voltage pulses • Magnetophoresis—a magnetic field • Ultrasound—low intensity ultrasound Systemic and topical delivery Transdermal technologies not only provide benefits for systemic drug delivery but also for local delivery of dermatological and cosmeceutical products, the latter not (in billions) Manufacturer Revenue Passive patches still dominate the transdermal market. Despite years of effort, the movement of active technologies into the market has been slow, and few have reached the market or been successful. In May 2011, FDA approved Sanofi Pasteur’s microneedlebased product, an influenza-virus vaccine called Fluzone Intradermal. In January, FDA approved Zecuity (sumatriptan), a single-use, battery-powered, iontophoretic patch for treatment of migraine in adults, developed by NuPathe Inc. (Conshohocken, PA). These achievements may open the way for development of more drugs using active technologies. Historically, many transdermal products have delivered drugs that provide treatment for hormonal deficiencies, help with smoking cessation, or manage pain. In addition to Sanofi and NuPathe, two other pharmaceutical companies have recently developed new products that treat other types of medical conditions. In January 2009, FDA approved Watson Pharmaceuticals’ Gelnique (oxybutynin), a gel for the treatment of overactive bladder. Last April, FDA approved UCB’s Neupro (rotigotine), a transdermal patch, for treatment of Parkinson’s disease and restless legs syndrome. In a market study published in September, Kalorama Information (New York) puts the current market for transdermal and transmucosal products at about $8.4 billion, with around $700 million being spent on the delivery technology. By 2017, the product value will be just over $10 billion, with delivery technology at $900 million (Fig. 1). Pharmaceutical companies initially became interested in transdermal technology for systemic drug delivery because it: 1) avoids problems related to gastrointestinal passage and hepatic first-pass metabolism in which absorption in the liver and the gut wall reduces the amount of drug available for systemic delivery; i.e., its bioavailability; 2) offers a controlled, continuous delivery of drugs; 3) provides the option of delivery once or twice weekly; and 4) facilitates easy termination of the drug. In addition to those benefits, companies have used the introduction of transdermal products as a method of extending the life cycle of products originally introduced in another form, such as capsules. Prior to entry of generic competitors into the market, a company can move the revenue base for its product from the original form to a transdermal solution. If patient acceptance is high, a barrier is created for generic products stuck with the original form of delivery. 2010 2011 2012 2013 2014 2015 2016 2017 Pharmaceuticals Using Delivery Technology Fig. 1. Transdermal drug and technology market, 2010–2017. Credit: Kalorama Information 30 Visit our website at March | April 2013 NuPathe’s Zecuity ionotophoretic patch (left) and a Theraject application (right). Credit: NuPathe, Theraject being subject to FDA’s stringent requirements regarding therapeutic effects. Transdermal delivery includes topical products such as gels that deliver drugs systemically, and many topical products are available for dermatological and cosmeceutical purposes. The skin is the common thread that unites systemic transdermal and local dermatological and cosmeceutical development, and many technology companies have sought partnerships with companies in all three fields. The cosmeceutical industry actually developed some of the technologies, and pharmaceutical companies later adopted them. Given the benefits of passive and active technologies for local and systemic delivery, companies will continue to develop pharmaceutical, dermatological, and cosmeceutical products, and both passive and active technologies provide opportunities for development of marketable transdermal drugs. Passive technologies Nanotechnologies Nanotechnologies seem to hold some hope of expanding the transdermal market. In 2010, NewGen BioPharma (Titusville, NJ) bought a transdermal platform, Micellar Nanoparticulates (MNP), from Novavax. That company had developed one transdermal product using MNP, Estrasorb (estradiol), which is currently on the market for treatment of symptoms of menopause. The platform improves the solubility and bioavailability of topically delivered products. Providing an increased residence time for an active pharmaceutical ingredient (API), the technology can reduce the dosage or the number of applications per day. MNP offers a solution for delivery not only of systemic transdermal products but also of topical local, oral, injectable, and ophthalmic products. Navdeep Jaikaria, NewGen’s CEO, indicates that MNP gives NewGen the ability to reformulate 60% of all small-molecule drugs. The company also has a platform for delivery of inhaled products and is developing a technology for largemolecule peptides. These peptides must have a stable conformation that withstands the high pressure under which formulations are produced; Jaikaria adds that only GRAS-listed (Generally Recognized As Safe) additives are used. Jaikaria has indicated that NewGen’s MNP platform holds promise for transdermal technology because it may improve patient acceptance of transdermal products. While common and well accepted in Asia, transdermal products such as patches can cause irritation and itching, and US consumers have not been as tolerant. NewGen’s nanoformulated, medicated lotions are nonirritating and are moisturizing rather than dehydrating, unlike patches in the first instance and gels in the second. NewGen is developing its own pipeline of drugs, currently 20 APIs that it has reformulated using the MNP platform. This year NewGen plans to launch an ophthalmic and a topical drug in India as well as a reformulation of Estrasorb that keeps estrogen in the skin longer. NewGen has used its technology to develop cosmeceutical products as well, one for hair regrowth and an anti-aging cream. The company will work with partners as a contract service provider, developing drugs using the platform. Jaikaria indicates that hormonal (steroidal) conditions, pain, urinary incontinence, erectile dysfunction, and smoking cessation are examples of the types of conditions that drugs using the platform can treat. The technology primarily permits delivery of small-molecule drugs, but Jaikaria says that it also will function with small peptides as long as conformation is not an issue. He says that any drug listed as BCS Class 2 (a measure of drug absorption), or that is poorly water-soluble, is a possibility for delivery. Like NewGen, Particle Sciences, a Bethlehem, PA, contract development and manufacturing organization, sees nanoparticles as a standard drug-delivery option. The company can incorporate APIs into particles using its proprietary technologies, with the possibilities ranging from an emulsion droplet to a nanoparticle of the API itself, from tens of microns down to several nanometers. Particle Sciences also uses an in-licensed technology, LyoCell, which combines a lipid-based approach with nanoparticles, with the particles having unique solubilization properties. Particle Sciences has focused on technologies for passive delivery of smallmolecule drugs but has also developed a proprietary system for targeting large molecules. Rob Lee, VP, says that Particle Sciences has worked on all routes of drug delivery, including transdermal patches,

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Pharmaceutical Commerce - March/April 2013
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Pharmaceutical Commerce - March/April 2013