Elsewhere in this issue, GBI research provided an overview of the oral drug delivery market, putting the cumulative annual growth rate at 10.3% for 2010-2017. We spoke to several companies that provide drug delivery services, to get their perspective on the opportunities available in the market.

Said Jeffrey E. Browne, Ph.D., technical director, Pharmaceutical Softgel Business Development at Catalent, “It’s a fact that the majority of compounds in today’s pharma companies’ pipelines are poorly soluble and/or poorly permeable. According to the Biopharmaceutical Classification Systems (BCS), these are BCS II, III and IV compounds. That creates a significant opportunity for companies that have technologies and expertise they can offer for the delivery of these challenging compounds.”

Mark Tomai, business development director at 3M Drug Delivery Systems, commented, “With the pressure traditional pharma companies face regarding the huge patent cliff and generic competition, we have noticed an increase in companies seeking manufacturing partners to not only be the technology providers but also to aid in varying degrees of the product development and regulatory process.”

He added, “To be successful in working with both large and small pharma companies, manufacturing partners must be flexible and continue to adapt business practices to fit with each customer’s needs while still meeting the client’s demand for efficacy, compliance and cost.”

Some companies are pursuing new technologies or niche offerings that can help them help developers with difficult compounds. Gary Wada, executive vice president of CMIC CMO USA, remarked, “We’ve seen an increase in the development of controlled release formulations, especially Wurster and Rotor fluidized bed processes that involve the use of solvents.”

Mr. Wada feels that Rotor-processing is a strong niche for his company. “Rotors can have much larger drug weight gains — up to 900% per batch — than those processed in a Wurster, and significantly faster processes by using powder feed layering,” he noted. “They also can apply controlled release coatings in the same equipment. Having solvent-capable laboratory through production scale rotor processors gives our customers more processing flexibility.”

Mr. Tomai at 3M DDS commented, “Technologies that provide efficient and user-friendly capabilities to meet the needs of regulatory systems, healthcare providers and patients are on the rise in the pharma industry. For example, needle-free drug delivery devices that provide increased patient convenience are becoming more important and offer companies an approach to differentiate their drug product and gain a competitive edge. Additionally, we have observed that the incorporation of patient-friendly features, such as adding a dose counter to metered dose inhaler devices, can have a significant impact on the success of a product, build patient loyalty and be an asset in regulatory approval.”

3M DDS recently added a fill line for its pressurized metered dose inhaler (pMDI) at its Northridge, CA site, creating a development-to-commercialization single-source bridge for that dosage form. Mr. Tomai noted, “Over the years, we have seen a shift by many pharma companies away from R&D efforts, even with the continued expansion of the global marketplace.

This shift in the industry has opened the door for drug delivery manufacturing partners to increase their offerings and serve as an expert in an array of areas, including drug delivery technology development, supply chain management, product development, regulatory navigation and analytical work, to name a few.”

There are plenty of novel delivery technologies in development and scale up, but the softgel is a major dosage form for poorly soluble compounds, and Catalent is the biggest player in the CDMO area for softgels.

Said Dr. Browne, “In softgels, we’re seeing a good deal of business focused on improving absorption and permeability of challenging compounds.” Through legacy companies, Catalent has been making softgels for 77 years, and in February, the company bought out its partner in Germany to solidify its global supply network for the dosage form.

Catalent has the lion’s share of softgels, but other players are trying to get into the market. At INTERPHEX this past May, Patheon launched P-Gels, its new softgel offering. Development and manufacturing work for P-Gels will be conducted at the Barranquilla, Colombia facility of Patheon’s partner Softigel, part of the Procaps Group.

We spoke with with Geoff Glass, Patheon’s executive vice president of global sales and marketing, about the company’s move into softgels. He said, “P-Gels is a softgel offering and related technology that we think is going to add much more value and flexibility to our clients and their patients. It provides an alternative to standard softgels and introduces some new technologies that we think are game-changers.”

One of those is technologies is Unigel, which has the ability to do fixed-dose combinations of multi-actives. Said Mr. Glass, “We can put softgels in softgels, tablets in softgels, granules in softgels, or any combination thereof. It can solve the issue of multiactives that don’t like to be in the same dose as well as tackling multiple solubility issues.” He told us that there are some innovative prototypes, utilizing some of the world’s biggest drugs. “We’ve done stability work on some very interesting tablets in some high-grade fish-oil compounds,” he commented. “Atorvastatin [generic Lipitor] has come off patent, and it’s been prototypes in some Unigel combinations that we think will be very innovative.”

Mr. Glass noted that Softigel’s parent Procaps owns several gelatin manufacturers, giving Softigel unique control over its supply chain. “We think this will be valuable to both generic companies and large pharmas that are looking for alternative, value-based supplies with more flexibility.

Unigel and the other P-Gels technologies will change the game. As we see many more of these BCS Class II to IV compounds coming out of development, emerging drug companies are going to need formulations that are going to solve the problem but also have downstream manufacturing capacity that they can scale in a cost-effective manner. We think it’ll be valuable for all sides of the industry.” Ultimately, said Mr. Glass, “P-Gels is going to offer more value, more flexibility, and more options.”

Dr. Browne at Catalent commented, “Everybody recognizes a lot of uses for softgels, so it’s not surprising that other companies would want to get into it. It’s difficult to do well, but if you look at the track record of the number of FDA products in the softgel area, I think it’s an interesting development.”

Patheon isn’t alone in forming partnerships to enhance its delivery offerings. Catalent recently joined with BASF to collaborate on bioavailability issues. According to a press statement from the companies, the alliance will offer “feasibility studies across multiple technologies, solid state chemistry, consulting and training, expert formulation services, excipients and optimal dose form development, to scale-up and supply.”

At the time of the announcement, Ralf Fink, vice president, Global Marketing at BASF Pharma Ingredients & Services, remarked, “With our broad portfolio of solubilizers and excipients for hot-melt extrusion, coupled with Catalent’s strengths in development, formulation and manufacturing, we are in a unique position to solve the solubility challenge. With this open alliance, we help our customers in the development and commercialization of drugs with poor bioavailability.”

Said Dr. Browne, “We’re excited about other delivery technologies at Catalent, including Zydis and Lyopan ODT tablets, Vegicaps technology (gelatin-free capsules that can expand the range of encapsulatable fill formulations), and OptiDose™. The Optidose technology allows you us to accurately position an inner tablet or pellets within an outer tablet; to include and isolate two incompatible drugs or modify the drug’s release profile by varying the thickness of the outer tablet surrounding the inner core tablet.”

He noted that there are a number of different release profiles achievable utilizing OptiDose. “It would also be a great boon for providing our customers product differentiation for their OTC product. OptiDose really offers something to differentiate your product from the competition, including the design of products which will catch the consumer’s eye in terms of appeal. For Rx, it’s the functional capabilities that Optidose brings such as modulating the release profile
of drugs.”

Mr. Tomai at 3M DDS was sanguine about the state of the business: “When you get down to it, client demands have remained consistent over the years: efficiency and product compliance remain top priorities. This has been emphasized with the expansion of available generic drugs in the marketplace, and it highlights how important it is for companies to have a reliable partner that possesses the resources and expertise to quickly respond in the first-to-file race.”