Wegmans School of Pharmacy, St. John Fisher University, Rochester NY.
University of Rochester Medical Center, Rochester NY.
Int J Pharm Compd. 2024 Sep-Oct;28(5):364-372.
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.
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.
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.
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.
医疗保健提供者经常需要为无法吞咽整片片剂或胶囊的患者寻找替代方案。许多新批准的即释（IR）固体口服药物在标签上带有一般的“切勿压碎”警告或类似说明，但没有任何解释。Uttaro 等人在 2021 年发表的一篇文章提出了一种用于风险评估的可压碎性分析策略，并展示了其在 ISMP 不压碎名单上一些不确定的 IR 药物中的实用性。本文就该主题进行了更新，并对新批准的 FDA 药物进行了可压碎性分析。
从 FDA 网站上获取 2020-22 年的新药批准信息。从清单中提取 IR 口服片剂和胶囊，并进行可压碎性分析。粉碎活动的范围定义为使用研钵和杵粉碎片剂或胶囊内容物，然后将粉末悬浮在室温下的普通水中，并在 2 小时内给药。可压碎性分析采用了一份清单，其中包含有关特殊剂型设计、危害药物状态、稳定性和药代动力学（PK）、制造商的非官方数据以及替代剂型可用性的问题。分析主要参考 FDA 批准产品的标签。NIOSH 出版物、FDA 橙皮书、专利和科学文献用于选定的药物。
从 2020 年到 2022 年，确定了 52 种新型 IR 口服片剂和胶囊的新药批准。其中，有 2 种产品已停产，有 10 种产品的标签上已经包含了特定的操作说明。其余 40 种产品的标签上要么有一般的“切勿压碎”声明，要么没有关于可压碎性的信息。对这 40 种产品进行可压碎性分析后发现，有 23 种产品压碎风险较低。然而，由于稳定性/PK 方面的考虑，其余 17 种产品不适合压碎。有 4 家制造商提供了与压碎或与液体/软食混合相关的非官方数据，并且没有一种产品有替代的口服液体制剂。
更新了可压碎性分析策略，并将其应用于 2020-22 年 FDA 批准的 40 种 IR 口服片剂和胶囊。总结表和突出的示例为药剂师和其他医疗保健提供者提供了实用资源，以做出有关剂型处理的明智决策，从而便于吞咽固体困难的患者给药。
