Weixian Shi, Lynn Dixon-Anderson
Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, NJ
Pharmaceutical tablets, typically packaged in bottles or blisters, must withstand significant physical stress as they undergo the series of transportation steps before reaching patients. Defects in tablets can lead to patient complaints. These defects can originate from a variety of sources, such as a formulation with insufficient compactability, a sharp edge due to a short landing on tablet tooling, or a weak coating layer. While such deficiencies are not always detected by typical mechanical integrity tests (hardness or friability) or downstream processes after compression, prolonged and uncertain exposure to mechanical stresses while being transported in the supply network can prompt the appearance of chips. Therefore, it is important to understand the propensity of chipping for a given tablet product. Current industry standards employ ASTM/ISTA drop tests to assess such risks. While the ASTM/ISTA drop test is indicative, it is normally conducted during late-stage drug product development, as the test requires a large amount of tablets. A failed test will trigger re-evaluation of the formulation and manufacturing process and creates last-minute tension, as the product was deemed as commercial-ready. The present study employs a computer simulation to mimic the ASTM/ISTA drop test along with a newly-developed failure stress test as a means to pre-screen formulation and tablet tooling, enabling the risk of chipping to be assessed earlier in the drug product development process. Preliminary results indicate it can be a powerful tool to guide rational design of formulation and process for pharmaceutical tablets. Select case studies will be highlighted to demonstrate the ability of the model to inform on chipping risks.