The pharmaceutical market is changing rapidly because of recent trends such as increasing generic-drug competition, decreasing patient subpopulations, variable product mixes and batch sizes, and the growing role of contract manufacturers. Drugmakers are forced to respond faster than ever to these market influences. Producers of solid dosage forms are looking toward flexible manufacturing strategies to help them remain competitive and profitable.
Flexibility in manufacturing means, in part, that operators can adapt equipment readily to frequently changing manufacturing requirements. An investment in flexible technology buys a degree of protection against an uncertain future.
Flexibility in tablet coating is achieved when the equipment accommodates the widest possible range of product-load conditions and is versatile enough to handle the gamut of coating processes (i.e., conventional film, functional, modified release, and active-drug layering).
Coaters generally accommodate a specified maximum drum charge of fully coated tablets, which often is referred to as the brim volume. The key to achieving flexibility, however, is the coater’s ability to coat much smaller volumes or short charges. The relationship between brim volume and the allowable minimum charge of cores is the turndown. For example, a coater that accommodates a brim volume of 200 L and successfully coats a charge of 50 L is said to have a 25% turndown. A high degree of manufacturing flexibility can be achieved if the coater is equipped with certain features to provide broad volumetric turndown and accommodate the associated range of tablet-bed configurations.
One factor that influences turndown is the gun-to-bed (GTB) distance, the distance between the spray gun and the bed surface. Adjusting the GTB distance and the angle of spray relative to the bed surface help coaters accommodate the desired range of drum charges.
A drum-charge volume may be defined to minimize the effects of mass on tablet abrasion and erosion. It may also be defined when a lot is divided into several equal charge volumes according to the capacities of upstream equipment. In many processes, the GTB distance and angle remain fixed throughout the entire process. But when the weight gain on the product is high (i.e., more than 20%), operators may need to reposition the gun-support hardware at predetermined intervals during the process as the bed height grows and the GTB distance shrinks.
To provide flexibility, suppliers offer three-axis, indexed positioning mechanisms that typically feature components with drilled holes and alphanumeric match marks. Quick-release pins hold the gun support in position once the desired orientation has been achieved. Adjustments should be easy to make, ideally without tools, and repeatable.
Another factor that affects turndown is the choice of mixing baffles. Having one or more sets of interchangeable baffles with alternate profiles may be desirable. Low profiles may be used when coating shallow beds, and high profiles when coating deep beds. Submerging the baffles in the bed during coating enhances mixing and helps prevent their direct exposure to the spray, which leads to residue buildup. Interchangeable baffles with different sweep angles and height profiles help operators select a profile to achieve good mixing of friable tablets when the drum speed cannot be increased.
When coating shallow drum charges, operators should match the exhaust-air path through the tablet bed to the bed height. When coating shallow beds, it is desirable to block off the upper portion of the mating exhaust-plenum opening to direct air through the bed, not around it. A range of plate sizes is useful in sizing the plenum opening from the top down to match the bed height.
Factors other than the coater also affect flexibility. Turndown of the process air-handling system (i.e., the difference between the maximum and minimum amounts of drying energy that can be supplied to the coater) helps achieve the widest practical range of airflow rate, temperature, and dewpoint conditions needed. Turndown of the solution-delivery system (i.e., the difference between the maximum and minimum solution-delivery rates), along with alternate pump types and interchangeable spray-nozzle setups of various sizes, helps provide flexibility in handling a wide range of solution properties and flow rates.
Flexibility in manufacturing coated tablets is an essential tool that helps drugmakers confront rapid market changes. Coating systems must be readily adaptable to coat today’s evolving array of products under optimal process conditions. A lack of flexibility would place unacceptable limits on products and processes and require manufacturers to accommodate the coater’s limitations.
Edward S. Novit is a former coating-systems product manager at Thomas Engineering, tel. 847.691.2942, [email protected].