A coat of many colours

Dr Jason Teckoe, technical director of BioProgress Technology, describes a new system for coating tablets that can enhance both appearance and toughness.

The coating of tablets serves several purposes, neatly summed up by the words toughness, appearance and function.Coatings protect tablets in transit and improve stability and shelf life; coloured coatings can improve the appearance, identification and consumer appeal of a tablet, and a smooth finish will facilitate ingestion.

Coatings may also mask tablet taste and odour, a necessity for some products such as ibuprofen, or iron or garlic tablets, and they can protect against irritation from medicines that can be corrosive to the mouth or digestive tract. Finally, some coatings will modify or control the timing or site of drug release.

The process of coating pharmaceutical tablets has been established for 150 years. Today, film coating is the most commonly used solution. This method usually involves spraying polymer contained in a solvent into rotating coating pans containing the tablets. Polymers used include hydroxy propyl methyl cellulose (HPMC), hydroxy propyl cellulose (HPC), sodium carboxy methyl cellulose (CMC) and acrylate polymers. Other additives such as plasticisers are used to improve the quality of finish, and colour may also be added at this stage.

The tablets are then dried to remove the solvent, leaving the coating around the tablet core. Film coating adds little to tablet mass and a clear coat retains the colour of the underlying tablet. If required, a sub coat can be applied to improve coverage.

Problems can occur with this film coating process. To ensure uniformity of coating thickness and colour, spray- rates, operating temperature and airflow rates for drying must be carefully controlled. The rotation speed of the coating pan must also be monitored. If too much coating solution is applied or drying speed is not effectively controlled, tablets may become sticky and clump together, and embossed logos may be in-filled. If drying conditions are not optimised then the film coating may crack or the film can dry to a rough texture resembling orange peel.

enteric coatings

Enteric coatings allow tablets to pass from the stomach into the intestine, where an alkaline environment dissolves the coating, allowing the drug to be absorbed through the intestinal wall. Enteric coatings may be applied in a single coat or in two coats, the first application being of the enteric polymer, such as cellulose acetate phthalate (CAP), and the second a water soluble polymer to improve appearance.

Sugar coating is less commonly used today than it was in the past, but it gives an infinitely better tablet appearance and has greater taste and odour masking qualities. Sugar coating is a complex process involving multiple steps: sealing; subcoating; smoothing; colouring and polishing. All these add to the expense of the procedure.

The most common problem associated with this process is uneven coating, which can produce misshapen tablets or variation in the surface colour. In addition, sugar coating can add 30-50% to the tablet weight and, of course, is calorific.

Gelatine coating is most regularly practiced in the US, where malicious tampering of over-the-counter medicines gave rise to the need for tamper-evident tablets. The process traditionally involves dipping tablets into a gelatine solution, but more recently, a method of enrobing a tablet with two layers of elastic gelatine film has been introduced. Whichever method is used, gelatine coating is expensive and has the disadvantage of consumer misgivings, as gelatine is derived mainly from animal renderings.

A new coating method, Tabwrap^TM, which uses pre-formed edible films to overwrap a tablet core, is now being introduced by BioProgress Technology. This company is pioneering the use of edible film technologies in a number of applications for the pharmaceutical and other industries. The first of its technologies to be licensed is called NRobe^TM, a novel dosage form that is being commercialised by the licensee, FMC Biopolymer.

edible films

Other technologies include using edible film strips as a delivery method for vitamins, minerals or supplements and active pharmaceutical ingredients (Soluleaves^TM, Wafertab^TM and Foamburst^TM), and the use of films for making liquid filled capsules (Swollo^TM and Septum^TM). The company develops both the production machines and manufactures the films required in the process. BioProgress has patents covering processes, machine design and film formulation.

Tabwrap was first shown to the industry at the ICSE exhibition in November 2005. It is a patented, high- speed continuous process for tablet coating, and an attractive alternative to traditional coating methods. Dry films are supplied to the manufacturer in rolls. Non animal-derived and GMO-free, they are suitable for patients with particular ethical or religious requirements.

A number of formulations have been developed to meet the requirements of different tablets; however, HPMC, CMC and pectin are most frequently used. These edible films dissolve rapidly, giving fast release of the actives. An enteric film is also in development.

In the Tabwrap process, tablets are introduced into the machine and located into individual cavities. A top film is then applied using a pressure differential to generate a tight fit around the tablet core. Any embossing on the tablet core will be adopted by the film. The top film is cut to shape, the machine then indexes the tablet and a second film is applied and cut. The two films will overlap, forming an effective tamper-evident seal.

This method of individually wrapping a tablet is a dry process. The films are of uniform thickness and colour, and there is no requirement for additional drying; an important advantage in handling formulations with heat-sensitive ingredients. Production speeds in excess of 100,000 tablets per hour are possible; however, since this is a continuous production method and not batch production, small tablet runs remain economical. Production may be carried out in standard manufacturing conditions.

enhanced appearance

An important feature of tablet wrapping is the enhanced appearance. The films are pre-produced and so may be supplied coloured, flavoured or even overprinted. The films have a high gloss finish, producing a tablet with the appearance of sugar or gelatine coating but with a much smaller increase in total tablet weight.

Since the wrapping is done in two stages, it is as easy to produce two-colour tablets as it is to produce single colour ones, simply by using two different coloured films. In addition, if the two film colours are carefully selected, it is possible to produce a tablet with three colour bands, the middle colour being formed at the overlap seam.

Edible films give excellent protection to a tablet whether in transit or in storage, with the film acting both as an effective barrier and as a carrier for flavours and colours. Product stability is usually equal to or better than that achieved by traditional coating methods and the overlapping airtight seal is tamper-evident. Little additional regulatory work is needed to switch from spray coating to edible film wrapping, as stability and dissolution tests are all that is usually required to submit a licence variation.

As the film wraps tightly around the tablet in the Tabwrap process, it does not suffer from the issues associated with traditional methods such as spray coating or sugar coating, which require adhesion to the tablet surface and where failure to adhere can lead to problems in the finished product, but with Tabwrap the risks of coating peeling off the product are minimised.

Modern tumble coating machines handle batches of hundreds of thousands of tablets. If problems occur, such as tablet chipping - damage to the coating on the edges of the tablets through excess pan rates or insufficient or uneven spray application of coating solution - then whole batches can be written off or will need to be manually sorted. Mistakes of this nature can be very costly. Tablet wrapping resolves many of these issues. The film covering will be even, there are no issues of adhesion to the tablet and the machine has relatively few parameters to control.

Particular interest in the possibilities of Tabwrap has come from companies that have recurrent problems with fragile tablets. Not all tablet formulations can be robust, as some ingredients and tableting excipients will not readily bind together.

Frequently, compression operators face the challenge of making tablet cores within exacting hardness parameters. Too much compaction and the tablet will not disintegrate in the body; too little compression and the tablet is in danger of breaking during the process of pan coating and automated packing. Broken tablets within the coating pan are a manufacturer's worst nightmare.

The advantage of the Tabwrap process is the individual handling of the tablets.

During the wrapping operation the tablet is located in its own pocket; once wrapped the fragile tablet is covered and therefore physically protected. This gentle, individual handling can offer substantial cost reductions for problem formulations.

An important additional advantage of this individual tablet handling is that, for the duration of the cycle time, when each tablet is held securely within its pocket in the Tabwrap machine, it is ideally positioned for printing. This use is coming to the fore with the debate on the requirement for 'Track and Trace' procedures, the main thrust of which is coming from the US FDA.

marking solution

A WHO report in 2003 estimated that counterfeit medicines accounted for 5-8% of the global drug supply; the FDA put the proportion closer to 10%, accounting for a staggering US$32bn of lost income for legitimate drug manufacturers. Aside from the cost implications of this problem, it is potentially deadly to patients who are taking vital medication.

The FDA has now issued guidelines for track and trace of cartons and packs. However, it is widely felt that the only solution will be to take identification down to the individual tablet level. Adequate marking methods, including ink-based technologies (often using minute bar codes) and radio frequency identification, already exist. But the more practical problem is how to apply these to the tablets. Tabwrap could provide an elegant and cost-effective solution without multi-stage handling of the products.

Edible film tablet wrapping has many advantages over traditional coating solution systems and is being welcomed by the pharmaceutical industry. It is a simple but effective technology offering many unique features that enhance the virtues of toughness, appearance and function of the finished tablet.