Oral thin films or orally dissolving films (ODFs) provide quick release of an active pharmaceutical ingredient (API) when placed on the tongue. ODFs provide an alternative to orally disintegrating tablets. These dosage forms are placed on a patient's tongue or any oral mucosal tissue. When wet by saliva, the film rapidly hydrates and adheres onto the site of application. It rapidly disintegrates and dissolves to release the medicine for mucosal absorption or, with modifications, allows for oral gastrointestinal absorption with quick-dissolving properties. These films initially were launched as mouth-freshening products containing ingredients such as menthol and thymol. These films are available as breath-freshening products from Johnson & Johnson (New Brunswick, NJ) and Wrigley (Chicago) in the United States and Europe and Boots (Nottingham) in the United Kingdom. Zengen (Woodland Hills, CA) produces a chloraseptic relief strip in the US to deliver benzocaine, a local anaesthetic to treat sore throats.
These ODFs contain film-forming polymers such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), pullulan, carboxymethyl cellulose (CMC), pectin, starch, polyvinyl acetate (PVA), and sodium alginate. Additional ingredients that are incorporated include plasticizers, sweetening and flavoring agents, coloring agents, saliva-stimulating agents, and thickening agents. Suitable uses for rapidly dissolving films are nicotine-replacement transdermal delivery, and as antiulcer and antihistamine drugs. Antipsychotic and sleeping-disorder drugs also are potential candidates for prescription products (1–4). Advantages of ODFs include improved portability, ease of administration, accurate dosing, cost-effectiveness, and improved patient compliance.
Manufacture of ODFsOne or a combination of the following process can be used in the manufacturing of ODFs: solvent casting, semisolid casting, hot-melt extrusion (HME), solid-dispersion extrusion, and rolling (1, 4). The most commonly used methods of film manufacturing are solvent casting and HME.
Specific types of equipment such as rollers are required for pouring the solution on an inert base. The clearance between the roller and the substrate determines the required thickness of the film. The final step, drying the film, removes the solvent and helps to obtain the finished product. Usually, glass, plastic, or teflon plates are used as an inert base for film casting. When the manufacturing technology is transferred from laboratory scale to production scale, several problems can be encountered. These problems can include the casting of the film, obtaining uniform thickness of the film, and proper drying of the sample. The selection of the proper type of dryer is needed in the final step of drying.
Once the films are dried, cutting, stripping, and packaging is done. Suitable size and shapes of films can be cut. The commonly available sizes of films are 3 x 2 cm2 and 2 x 2 cm2. Selection of the packaging container is an equally important parameter for the ODF. The packaging container should provide sufficient mechanical strength to protect the film during shipping and from external factors such as temperature and humidity. Depending upon the characteristics of the film, single-unit containers and multiple-unit dispensers can be selected. The packaged films are inspected before being packed into a secondary packaging container (4).
Hot-melt extrusion . HME is commonly used to prepare granules, sustained-release tablets, and transdermal and transmucosal drug-delivery systems (5). The HME process recently has gained popularity in the pharmaceutical industry. Based on knowledge from the plastics industry, formulators can extrude combinations of drugs, polymers, and plasticizers into various final forms to achieve desired drug-release profiles (5). Processing films by this technique involves shaping a polymer into a film via the heating process rather than through the traditional solvent-casting method (4).