Insights into Thermal Interactions in Frozen Pharmaceutical Vials: Effects on Ice Nucleation Times and Inhibition.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY Pharmaceutical Research Pub Date : 2024-06-01 Epub Date: 2024-05-20 DOI:10.1007/s11095-024-03713-2

Roberto Pisano, Jessica Semeraro, Fiora Artusio, Antonello A Barresi

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Abstract

Purpose: This study investigates the thermal interactions between adjacent vials during freezing and assesses their impact on nucleation times.

Methods: Various loading configurations were analyzed to understand their impact on nucleation times. Configurations involving direct contact between vials and freeze-dryer shelves were studied, along with setups using empty vials between filled ones. Additionally, non-conventional loading configurations and glycol-filled vials were tested. The analysis includes 2R and 20R vials, which are commonly utilized in the freezing and lyophilization of drug products, along with two different fill depths, 1 and 1.4 cm.

Results: The investigation revealed that configurations with direct contact between vials and freeze-dryer shelves led to substantial thermal interactions, resulting in delayed nucleation in adjacent vials and affecting the temperature at which nucleation takes place in a complex way. In another setup, empty vials were placed between filled vials, significantly reducing thermal interactions. Further tests with non-conventional configurations and glycol-filled vials confirmed the presence of thermal interactions with a minimal inhibitory effect.

Conclusions: These findings carry significant implications for the pharmaceutical industry, highlighting the role of thermal interactions among vials during freezing and their impact on the temperature at which ice nucleation occurs.

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洞察冷冻药瓶中的热相互作用：对成冰时间和抑制作用的影响

目的：本研究调查冷冻过程中相邻小瓶之间的热相互作用，并评估其对成核时间的影响：分析了各种装载配置，以了解它们对成核时间的影响。研究了小瓶与冻干机架直接接触的配置，以及在装满的小瓶之间使用空小瓶的设置。此外，还测试了非常规装载配置和乙二醇填充小瓶。分析包括药物产品冷冻和冻干过程中常用的 2R 和 20R 小瓶，以及两种不同的填充深度（1 厘米和 1.4 厘米）：调查显示，小瓶与冻干机搁架直接接触的配置会产生大量的热相互作用，导致相邻小瓶的成核延迟，并以复杂的方式影响成核时的温度。在另一种设置中，空小瓶被放置在已填充的小瓶之间，从而大大减少了热相互作用。使用非常规配置和乙二醇填充小瓶进行的进一步测试证实了热相互作用的存在，但抑制作用很小：这些发现对制药业具有重要意义，突出了冷冻过程中小瓶之间热相互作用的作用及其对冰核形成温度的影响。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.