. Similar to other oral immediate- release drug delivery forms in which the dosage form contacts the tongue, taste-masking
plays a critical role in the success of a product's acceptance and is an equally critical component of the film's formulation.
Many of the same taste-masking techniques used to formulate syrups and soft-chew oral dosage medications can be used in OTFs.
Traditional flavor and sweetener combinations, encapsulation or particle coating of the API, and complexation with ion-exchange
resins are some of the techniques that may be successfully applied for masking bitter-tasting or objectionable materials in
OTFs. When possible, taste-masking techniques resulting in discrete particles larger than 250 µm should be avoided, as these
could potentially present uniformity challenges in the finished dosage form (7).
Manufacturing oral thin films
Because OTFs may incorporate APIs with a narrow therapeutic index, tight manufacturing tolerances must be held to deliver
a uniform pharmaceutical product. The manufacturing techniques used for OTFs are built upon the proven liquid-casting techniques
used for decades in the commercial manufacturing of advanced polymers and coatings found in transdermal drug-delivery systems
(4), in vitro diagnostic devices, and other medical devices (see Figure 2).
Casting and drying.
Liquid casting is the preferred manufacturing method over 100% solids extrusion because it avoids exposing APIs to elevated
temperatures that may cause drugs to degrade. Liquid casting also allows for film uniformity and low variability with regard
to mass. A typical relative standard deviation (RSD) for uniformity testing of an oral thin-film batch prepared by liquid
casting is on the order of 1–2% RSD (7).
The casting station transfers a bulk solution from the mixing vessel into a thin film on the surface of a release liner (2)
in widths of typically 30–120 cm. The preferred finished film thickness is typically 12–100 µm, although various thicknesses
are possible to meet API loading and dissolution needs. Multiple casting techniques may be selected on the basis of the fluid
rheology, desired applied mass, and required dosage uniformity. These coating techniques include knife-over-roll, reverse
roll, slot-die, gravure cylinder, and Meyer rod coating.
Drying of the cast bulk liquid is accomplished by passing the coating through an oven or series of ovens to evaporate any
solvent(s) used to prepare the liquid. The dried film is wound into a roll and wrapped in foil packaging to ensure environmental
protection during handling and storage, before being processed into single, pre-measured unit doses (10).
Packaging and converting
. The converting and packaging stage also provides product flexibility to drug manufacturers. The rolled film can be die-cut
into any shape or size or slit into narrower rolls as required for the application. For branding purposes and to meet industry
regulations, converters may choose to print information directly onto the film unit doses before packaging.
Currently, most drug-containing films are packaged by unit in primary packaging. The specific number of unit doses is then
organized within a secondary shelf carton. To provide product stability during the expiration dating period, several packaging
suppliers offer multilayer flexible-film and foil-laminated products with high moisture barriers. Industry packaging standards
vary by product and market, and requirements should be discussed for each product during the design phase. Criteria that may
be taken into consideration include the need for unit-dose packaging, barcode labeling, and the content in instructions for
use, child-resistant seals, and senior-friendly packaging (2).