Today, pharmaceutical companies show heightened interest in reformulating their existing drugs into new dosage forms, and the strategy has many arguments in its favor. One relatively new dosage form is the orally dissolving strip, a thin film formulated with hydrophilic polymers that rapidly dissolves on the tongue. This format is currently used for some therapeutic products such as Novartis’s (Basel) “Triaminic” cold-relief treatment.
The equipment needed to manufacture orally dissolving strips is familiar to the pharmaceutical industry. It includes standard mixing or compounding vessels, coating lines, drying ovens, and packaging equipment such as standard pouching machines.
One common method of producing orally dissolving strips entails solvent casting and film coating. First, a manufacturer mixes a solution of active pharmaceutical ingredients (APIs) and film-forming excipients with volatile solvents. Next, operators cast a thin coat of solvent blend onto a moving, inert substrate. They then move the coated film through a drying oven to evaporate the solvent before die-cutting the dried film into strips.
Manufacturers also can produce orally dissolving strips using hot-melt extrusion (HME). This technique involves melting an API–excipient polymer, then extruding it through a die under molten conditions. Finally, the thin film is cooled to room temperature and die-cut into small strips. Extruders are not common in the pharmaceutical industry, however, and this method would call for many manufacturers to invest in the necessary equipment.
Switching from development-scale to commercial-scale production of orally dissolving strips poses particular challenges. The speeds of the coating and drying operations are the most important direct influences on production, says Albert Manser, chemist at Werner Mathis (Oberhasli, Switzerland). These speeds must be increased to appropriate levels for commercial-scale throughput. The wet-coating thickness and the properties of the coating solution affect production by limiting the product’s drying speed and final dry thickness. These properties can be adjusted to enable efficient commercial-scale production.
Selecting the correct type (e.g., horizontal-nozzle, bow, or hot-flue) and number of dryers also helps operators achieve production capacity for a continuous-coating line, says Manser. Companies are increasingly adopting continuous-coating equipment and corresponding dryers in their research and development departments. “This is a great advantage to scale-up because web-guiding and drive systems, including machine controllers, give perfect basic information for high-capacity manufacturing,” Manser says. Incorporating extra dryers into the line sometimes increases process speed, he adds.
During scale-up, companies must take care that air and moisture do not become incorporated into the orally dissolving strips, says Avani Amin, principal and in-charge director of the Institute of Pharmacy at Nirma University of Science and Technology (Ahmedabad, Gujarat, India). The incorporation of air would produce an uneven film surface, and moisture would change the film’s mechanical properties (e.g., tensile strength, flexibility, and folding endurance), Amin explains. A manufacturer should observe strict humidity and moisture controls in the manufacturing area and use optimal vacuum machines.
Other critical parameters to consider during scale-up generally revolve around the properties of the API, according to Patty Frey, director of operations at ARx (Glen Rock, PA). For example, heat and shear sensitivity, the form in which the API is readily available, and the materials with which the API will react (e.g., solvents) must be evaluated.
“We are fortunate, in that the manufacturing techniques for orally disintegrating films are well understood and lend themselves to holding exceptionally tight tolerances throughout the process,” says Frey. Scale up should be no more challenging for the production of orally dissolving strips than for other common dosage forms.
On the other hand, manufacturers are looking for ways to make these well-understood processes more sophisticated. For example, simultaneous segregated coating (e.g., side-by-side coating or spot coating) could separate APIs that would otherwise interact with or neutralize each other. No pharmaceutical company is producing commercial quantities of orally dissolving strips using these methods, according to Frey. Manufacturers are investigating whether simultaneous segregated coating would be cost-effective or change therapeutic outcomes. And pharmaceutical companies still need to develop an efficient way to integrate these manufacturing strategies.
Pharmaceutical companies that seek new dosage forms for their existing products might find orally dissolving strips to be a format worth considering. The dosage form’s portability and ease of use appeal to patients, and the product can be created using equipment and procedures familiar to the industry. For these reasons, the coming year may see more manufacturers pursue orally dissolving strips.