Crushability Analysis of Immediate-Release Oral Tablets and Capsules from the 2020-22 FDA Novel Drug Approvals.

Abstract

Purpose: Healthcare providers often need to explore alternative options for patients who are unable to swallow whole tablets or capsules. Many newly approved immediate-release (IR) solid oral drugs carry a general "do-not-crush" warning or similar statements in their labeling without any explanations. A 2021 publication by Uttaro et al. presented a crushability analysis strategy for risk assessment and demonstrated its utility for some uncertain IR drugs on the ISMP do-not-crush list. This article provides an update on the topic and performs the crushability analysis of newly FDA-approved drugs.

Methods: The novel drug approvals from 2020-22 were obtained from the FDA website. The IR oral tablets and capsules were extracted from the lists and subjected to crushability analysis. The scope of crushing activity was defined as crushing the tablets or capsule contents using a mortar and pestle, followed by suspending the powder in plain water at room temperature and administering the dose within 2 hours. The crushability analysis employed a checklist of questions regarding special dosage form design, hazardous drug status, stability & pharmacokinetics (PK), unofficial data from manufacturers, and availability of alternative dosage forms. The FDA-approved product labels were used as the main references for the analysis. NIOSH publications, FDA Orange Book, patents, and scientific literature were used for selected drugs.

Results: From 2020 to 2022, 52 novel drug approvals were identified as IR oral tablets and capsules. Among them, 2 products were discontinued, and 10 already included specific manipulation instructions on their labels. The remaining 40 products had either a general "do-not-crush" statement or no information regarding crushability on the labels. The crushability analysis of these 40 products revealed that 23 products exhibited a low risk for crushing. However, the remaining 17 products were not suitable for crushing due to mostly stability/PK concerns. Four manufacturers had unofficial data related to crushing or mixing with liquids/soft foods, and none of the products had alternative oral liquid dosage forms.

Conclusion: The crushability analysis strategy was updated and applied to 40 IR oral tablets and capsules approved by FDA during 2020-22. The summary table and highlighted examples serve as a practical resource for pharmacists and other healthcare providers to make informed decisions regarding dosage form manipulation to facilitate dose administration in patients with difficulty swallowing solids.