The Challenge for Manufacturers in Tablet Splitting

PTE:What are the problems or risks associated with splitting unscored tablets, especially if they are film-coated or modified-release tablets?

Kettler: A film-coated tablet is coated for a reason: to enhance the patient's ability to swallow the tablet, to allow the tablet to pass through the stomach before disintegration in the small intestine, to mask odor, or to provide strength and stability to the formulation encased by the coating. Splitting a coated tablet will violate the coating and thus minimise the function of the coating. A modified-release tablet should not be split as it may alter the time-release profile of the original formulation and consequently alter the patient's response to the original dosage. Enteric-coated tablets are covered by the same caveat and modification of the coating in any way will compromise both delivery and function of the dose.

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PTE:How different is the tableting process for scored tablets compared with unscored tablets in terms of the technology and equipment involved, quality control and quality assurance protocols?

Kettler: The design of the scored tablet will dictate the compression tooling to be used in the tablet press. The tablet dimensions, hardness, disintegration and content uniformity must meet the critical quality attributes as registered by the manufacturer. Operation of the tablet press is no different for a tablet with a score and one that is not scored. While there is guidance with respect to assessing the quality attributes of tablets that have been split, there is currently only recommended testing of the tablets that result from the splitting of the original tablet.

PTE:To ensure that tablets can be split evenly with good dosage content uniformity, what factors do tablet manufacturers need to take into account?

Kettler: Design of the tablet and ultimately the performance of the dosage form to deliver the availability of the API will dictate the tablet shape and configuration of the score. Considerations for the targeted patient population need to be taken into account; for example, the ability of the targeted patient population to split a tablet should be factored into the design of the scored tablet. Elderly patients or those with limited strength in their hands will require a tablet that is readily split, perhaps at the expense of overall tablet strength. There exists technology that allows for very accurate dosage control for split tablets by scoring the tablet in an area of the tablet that is devoid of any API, thus enhancing the probability that the dosage delivered is as prescribed.

PTE:What are the common challenges involved in the formulation, manufacturing and testing of scored tablets? What key factors must manufacturers take into consideration, especially in ensuring that regulatory requirements are met?

Kettler: This is a quality-by-design opportunity. The challenge is to design a tablet with quality that meets the patient's dosing requirements and control the formulation and tableting processes to the targets required to yield a tablet that provides the patient with the dosage performance that delivers the desired efficacy. Start with good tablet and process designs, and the output should be a tablet that meets requirements regardless of whether it is split or not. Is it easy? No, it is not. Communication among all the parties involved is essential so that one team's assumptions do not impact another team's expectations. It takes experienced, innovative formulators to work with the tooling company to design the tablet and then utilize formulation science to meet the dosage requirements for a presentation that can be packaged to ensure stability and ease of use by the patient. Pharmaceutical engineers, capable of controlling and maintaining the unit operations involved, are key to lot-to-lot comparability and performance of the end product.