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 ODFs
One 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.
Table I: Comparison of the solvent-casting and hot-melt extrusion methods for manufacturing orally disintegrating films.
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Solvent-casting method.
The ODF is preferably formulated using the solvent-casting method, whereby the water-soluble ingredients are dissolved to
form a clear, viscous solution. The API and other agents are dissolved in smaller amounts in the solution, and combined with
the bulk drug. This mixture is added to the aqueous, viscous solution. The entrapped air is removed by vacuum. Deaeration
is necessary to obtain uniform film property and thickness. The resulting solution is cast as a film, allowed to dry, and
cut into pieces to the desired size. The properties of the API play a critical role in the selection of a suitable solvent.
The physicochemical properties of the API should be considered. These properties include compatibility of the API with other
film-forming excipients, compatibility with solvents, the polymorphic nature of the API selected, and temperature sensitivity.
Manufacturing and packaging ODFs requires special precaution to be taken to control the effect of moisture. Figure 1 indicates
critical factors involved in ODF manufacture using the solvent-casting method. Stability of the film and its mechanical properties
are significantly affected by the presence of moisture. Another factor requiring strict control is temperature. Controlled
temperature conditions are required for maintaining the viscosity of the solution and temperature sensitivity of the API (4).
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).
