Orally disintegrating tablets (ODT) and fast dissolving films or dissolvable oral thin films (OTFs) have continued to expand in sales and launched as patient compliant, and convenient products efficiently addressing issues for pharmaceuticals as well as nutraceuticals that have been traditionally administered as oral solid dosages.
Fast-dissolving thin oral films are rapidly gaining interest in the pharmaceutical industry over disintegrating tablet technology because they are handy with patients having difficulties in swallowing or chewing solid dosage forms. In Technology Catalysts' recently-released report on 'orally disintegrating tablet and film technologies' (3rd Edition), the company identified over fifteen companies actively developing OTF delivery technologies that enable the shift from a tablet form to a fast-dissolving and highly water-soluble wafer or film. In addition, the report identifies nine launched OTF pharmaceutical products as well as 47 OTF products in the pipeline being developed by 12 companies. Technology Catalysts forecasted the market for drug products in oral thin film formulations to be valued at $500 million in 2007 and could reach at $2 billion by 2010.
OTFs evolved from the confectionery and oral care markets over past decade in the form of breath strips and became a novel and widely accepted dosage form by consumers for delivering vitamins and personal care products. Companies' expertise in formulating polymer coatings for transdermal drug delivery focused on transitioning this technology to OTF. Today, OTFs are a well proven and globally accepted technology for the systemic delivery of active pharmaceutical ingredients (APIs) for over-the-counter (OTC) medications and are in the early- to mid-development stages for prescription drugs. It consists of thin polymeric films (50-150 microns thick) constituting drug which dissolves rapidly in oral cavity on moist mucosal surfaces or the film rapidly hydrates and adheres onto the site of application.
In contrast to other existing rapid dissolving dosage forms, which consist of lyophilisates, the rapid films can be produced with a manufacturing process that is competitive with the manufacturing costs of conventional tablets. Handling, transportation, and storage problems are also associated with orally disintegrating tablets (ODTs) due to their high porosity, low mechanical strength and low density. Special packaging requirement are necessary for ODTs because of high friability. There is also a major concern regarding the ease of swallowing and even the possibility of choking when using ODTs. But from brighter perspective, films can be produced by easily industrially feasible and scalable solvent cast methods or hot-melt extrusion technologies. It is well known that the solvent cast method suffers from several disadvantages over the hot-melt extrusion method due to the solvent residues within the film and the environmental risks in the case of organic solvent. In addition, extrusion facilities are economic as compared to solvent cast ones. Thus, from commercial point of view fast dissolving films can be utilized further in the life cycle management of existing products.
Fast dissolving films mainly compose of thin polymeric films with plasticizers, surfactants, flavour, colours etc. A typical composition contains the following
Drug 1-25%
Water soluble polymer 40-50%
Plasticizers 0-20%
Fillers, colours, flavours etc. 0-40%
The OTFs have a larger overall surface area because they are typically 25 to 40 mm in length and about 20 to 30 mm in width, and it is this larger surface area combined with thinness of OTFs that allow their rapid dissolution.
OTFs are formulated from combinations of polymers to have ideal film characters. The polymers are usually water soluble grades of cellulose ethers, polysaccharides, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycols etc.
The plasticizer improves flexibility and reduces brittleness of the film. When the plasticizer concentration exceeds its limit, it causes phase separation and physical exclusion of the plasticizer leading to a white residue on edible films which are referred to as "blooming" or "blushing".
In addition other additives incorporated are lubricants, anti-tacking agents to modify adherence of film. Other ingredients like preservatives, colours, and opacifires included at specified levels. Flavouring agents not only have effect on organoleptic perception but also on film strength thus, liquid flavor oils that disperse well in final formulation are generally explored.
Currently, most drug-containing films are packaged by unit in primary packaging. To provide product stability during the expiration dating period, several packaging suppliers offer multilayer flexible-film and foil-laminated products with high moisture barriers. Criteria that may be taken into consideration include the need for unit-dose packaging, barcode labelling, and the content in instructions for use, child-resistant seals, and senior-friendly packaging. The finished products OTFs are then generally subjected to release tests similar to those for typical solid oral dosage forms such as weight, assay, related substances, content uniformity, moisture content, mechanical tests (such as tensile strength and percent elongation), drug release by dissolution and microbial testing.
Currently marketed products
The other technologies developed to explore utilization of mouth dissolving thin films are Soluleaves, Wafertab, Foamburst and Xgel.
The growing success and popularity of OTFs recently in global market is evidence to the need for effective taste masked, "without water" pharmaceutical formulations. Fast dissolving films being a natural evolution of fast dissolving drug delivery systems have prominent advantages over conventional dosage forms and orally disintegrating tablets. Due to their requirement during the emergency cases and high patient compliance, OTFs have emerged to be advanced and consumer friendly dosage forms. Therefore motivation for development and exploration of this dosage form in the public and private sector is the need of the hour in the global movement. These films can be manufactured through non-sophisticated and uncomplicated equipment and procedures. Due to these, fast dissolving films have economically feasible developmental futuristic opportunities.
Authors are faculty, Department of Pharmaceutical Sciences and Technology. Institute of Chemical Technology, Matunga, Mumbai.