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Aptalis Pharmaceutical Technologies: New formulations drive value

Posted on 28 February 2012

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Written and published by partneringNEWS.

By controlling the taste, bioavailability or timed release of drugs, Aptalis Pharmaceutical Technologies can help drug developers recoup the USD 30 billion lost to the industry each year because of patients not refilling—or never filling—their prescriptions. Controlling these factors also may improve compliance, lower dosage amounts, reduce side effects and improve efficacy as well as extend product life and, in some cases, expand the market for a given drug.

Aptalis Pharmaceutical Technologies, the drug delivery division of Aptalis Pharmaceuticals, has developed unique technologies that can be combined or applied singly to small molecules for immediate or custom-release oral dosage forms that combine high product reliability, pleasant taste and excellent mouth-feel. The company has more than 370 patents for its technologies, allowing it to meet very specific customer requirements using technologies that are strongly protected.


Patients frequently say taste is a tablet’s most important attribute, especially if administered without water, but “taste-masking, 80 percent of the time, is done as a life cycle management exercise,” noted Robert Becker, PhD, chief scientific officer. “By making drugs more palatable, taste-masking improves compliance and extends product reach to patients who are more taste-sensitive—including geriatric and pediatric patients—which is a major factor in patient adherence,” he said, as more than 150 aversive tasting drugs exist in the US alone.

The Aptalis technology combines taste-masking with oral disintegrating product technology. AdvaTab® orally disintegrating tablets (ODT), for example, disintegrate in the mouth in less than 30 seconds, without water. It can be combined with Microcaps® taste- and odor-masking and/or Diffucaps® customized release profile technologies. Microcaps uniformly microencapsulates drug particles via a proprietary coacervation technique.

“We have a technology that performs at the level of the drug powder or crystal and protects the actual drug from being dissolved by saliva,” Becker said. Called Liquitard®, it is a powder formulation that patients can sprinkle on food or into liquid from a single-dose sachet or stick pack. It is available in a wide range of flavors and is compatible with Aptalis customized release technologies, thus providing an opportunity to customize formulations to meet many specific needs.

The challenge for drug developers, Becker elaborated, is that “coating a product with a protection layer usually delays the release of the drug in the gastrointestinal tract, where you want quick dissolution to ensure that this formulation is bioequivalent to the reference drug.” Aptalis Pharmaceutical Technology has a history of overcoming that challenge using pharmacokinetics data as proof.

“Aptalis is the only company applying this technology,” Becker noted. “We have a lot of process knowledge behind us, generated over many years. No other company in the world is able to manufacture product as reliably with this process.” And, he added, “the process is highly effective and offers economies of scale.”


Aptalis resolves bioavailability enhancement issues using its Biorise® and Diffucaps® technologies. As Becker elaborated, “For drug developers, the issue is that many molecules are poorly soluble, yet if the drug is not soluble it cannot be absorbed and therefore cannot reach its site of action.” The number of poorly soluble drugs peaked in the 1990s and remains high, he says. That is partially attributable to high throughput screening, which has identified many compounds with high efficacy but poor development properties.

Many companies in this highly competitive area are working to make these drug compounds more soluble. “No approach is broadly applicable, however, and each has its specific advantage,” Becker said.

Biorise improves the rate and extent of drug solubilization in the GI tract, which can speed action, improve bioavailability, lower dosage amounts, and/or improve dosing effectiveness of poorly soluble drug candidates. The Aptalis solubility enhancement factor is in the highest range. “We can increase solubility by at least a factor of 10, allowing pharmaceutical companies to deliver the full efficacy of a given dose without overloading the patient’s system,” Becker said. Diffucaps patented technology is used to formulate products with release profiles designed to eliminate drug fluctuations to more accurately target drug tolerability limits and, therefore, decrease side effects. This technology can be applied to drugs with an extreme pH-dependent solubility profile, as in environments with pH above 8.0, or in physiological fluids.

Through these technologies, drug developers of a New Chemical Entity can advance poorly soluble compounds that otherwise would be discontinued. For already marketed drugs, these technologies can reduce dosage amounts and frequency of administration, enhancing patient safety, compliance and convenience.

Release profiles

Aptalis also is a leader in customized drug release, designing a wide range of release mechanisms and profiles, Becker said. As he explained, “When you swallow a pill, you typically have efficacy during a very short period of time—perhaps three hours—before the drug is eliminated.” A typical drug regimen can require twice- or even thrice-daily dosage, leading to peaks and troughs in the amount of drug available to the body, and several hours of unavailability. Studies, however, indicate better efficacy, safety and compliance rates—and, thus, improved healthcare outcomes—with once-daily dosing versus multiple daily dosings. Therefore, a drug’s formulation can become a competitive advantage.

Customized release profiles can be tailored to optimize a drug’s therapeutic performance and reduce the potential for over medication. For example, a time-modified release profile can be developed for drugs requiring rapid onset of action followed by maintenance of the therapeutic plasma level within a single dosage unit. Alternatively, time pulsatile release may be optimal for compounds needing rapid escalation of physiological drug levels after a defined delay.

In contrast, combination products may require different release profiles for each active ingredient. Other drugs may be part of a combination product that requires different release profiles for each active ingredient. Applying custom release profiles facilitates drug release in a specific region of the GI tract for optimal absorption and efficacy. Aptalis can customize dosage profiles to optimize delivery of each drug.

“Our customized release technology can provide a constant flow of drug over a specific time, so we can release for 10 or even 24 hours in the gut,” Becker said. This improves drug tolerability by avoiding the peak drug concentrations associated with multiple dosings, thereby assuring continuous efficacy.

Modified release products, historically, are developed as second generation products to manage the life cycle and extend patent protection. But, in some cases, it also opens new indications.

Currently, Becker said, “we are collaborating with the University of Genova to develop a highly innovative approach that combines customized release technology with what we call muco-adhesion.” Still in the very early research stage, the goal is to adhere the dosage form to the wall of the gastrointestinal tract and to ensure it remains there for prolonged release. There appear to be multiple advantages, including the ability to treat local diseases in the gut and to divorce dosage from gastro activity. Project details will be presented in July at the Controlled Release Society meeting.


R&D and manufacturing occur in integrated facilities with shared development teams for scale-up and manufacturing. Locations in Europe and the US serve a global market, and are audited regularly by regulatory agencies from the US, Europe, Asia and the Middle East.


“BIO-Europe Spring® is a good opportunity to build relationships and to discuss constantly-emerging technologies,” Becker said. “We have a very extensive exchange on a scientific level with our customers. Each project provides new scientific knowledge and insights, which are applied to the development of new technologies. Our primary goal is to make our technology as flexible as possible through the entire drug development process, offering a modular approach,” Becker concluded.


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