US FDA has issued a draft guidance on critical quality attributes that should be assessed during the development of chewable tablets. The regulatory authority has asked the industry to comment on the same and revert before August end.
The recommendations in this guidance apply mainly to new drug applications (NDAs), abbreviated new drug applications (ANDAs), and certain chemistry, manufacturing, and controls (CMC) supplements to these applications.
Chewable tablets are an immediate release (IR) oral dosage form intended to be chewed and then swallowed by the patient rather than swallowed whole. They should be designed to have a pleasant taste and be easily chewed and swallowed. These tablets should be safe and easy to use in a diverse patient population, paediatric, adult, or elderly patients, who are unable or unwilling to swallow intact tablets due to the size of the tablet or difficulty with swallowing. The availability of safe, easy-to-use dosage forms is important in clinical practice. Chewable tablets are available for many over-the-counter (OTC) and prescription drug products.
The United States Pharmacopoeia (USP) recognizes and differentiates between two types of chewable tablets:. One is chewed for ease of administration, and the other crushed before swallowing to avoid choking to ensure the release of the active ingredient. The concepts in this guidance are applicable to both types of chewable tablets, said the regulatory authority.
Adverse events for chewable tablets can include gastrointestinal (GI) obstruction resulting from patients swallowing whole or incompletely chewed tablets, as well as tooth damage and denture breakage resulting from excessive tablet hardness. A related potential adverse event that sponsors should also consider is esophageal irritation from chewable tablets.
A review of numerous approved drug product applications for chewable tablets revealed that in certain cases critical quality attributes such as hardness, disintegration, and dissolution were not given as much consideration as may have been warranted. This was evidenced by instances of incomplete monitoring and a wide variation in analytical procedures.
The regulator note has stated that its latest draft guidance describes the critical quality attributes that should be considered when developing chewable tablets and recommends that the selected acceptance criteria be appropriate and meaningful indicators of product performance throughout the shelf life of the product.
A variety of physical characteristics should be considered in the manufacturing process for chewable tablets. An ideal chewable tablet should be: Easy to chew, palatable, of appropriate size and shape and able to disintegrate readily to minimise aspiration and facilitate dissolution.
Critical quality attributes for chewable tablets should include hardness, disintegration, and dissolution, as well as all factors that may influence drug bioavailability and bioequivalence. In addition, careful attention should be given to tablet size, thickness, and friability, as well as taste, which may impact the ability or willingness of a patient to chew the chewable tablet. No single quality characteristic should be considered sufficient to control the performance of a chewable tablet. Instead, the goal should be to develop the proper combination of these attributes to ensure the performance of the chewable tablet for its intended use.
Even during conduct of pivotal clinical studies, information should be collected on whether the chewable tablets swallowed were intact. If the shape and size of chewable tablet posed a choking or bowel obstruction risk and whether water was used to aid swallowing and its volume. The subject’s sensory experience like taste, mouth feel, and aftertaste needs to be reported, stated the regulatory authority.