Lyophilization Technology, Inc., 30 Indian Dr., Ivyland, Pennsylvania, USA.
Pharm Res. 2004 Mar;21(3):536-42. doi: 10.1023/B:PHAM.0000019309.23212.d3.
Understanding tubing vial design features that influence sublimation rate provides insight into the development of a more time and cost efficient lyophilization cycle.
A Plackett-Burman screening experiment was initially used in evaluating multiple design features to predict those that have a statistically significant effect on sublimation rate. Sublimation rates of vials with intentional nominal and extreme dimensions were measured and directly correlated to glass vial design features using conservative and aggressive lyophilization parameters to amplify subtle differences in rates. Purified water, USP was used to alleviate the inhibition to mass transfer due to the presence of excipient and drug substances. Further studies quantified the effect of bottom concavity on sublimation rate while using model preparations to illustrate the impact of processing crystalline and amorphous material.
The results from the Plackett-Burman statistical screening experiment indicate that sublimation rate is influenced by glass type, vial diameter, bottom radius, and fill volume. Results from further studies verify that the influence of concavity on sublimation rate is statistically insignificant.
The results from the Plackett-Burman screening experiment reflect that vial diameter has the greatest impact on sublimation rate. Further studies confirm that various bottom concavities do not substantially influence sublimation rate.
了解影响升华速率的管瓶设计特征，有助于开发更省时、更经济的冷冻干燥周期。
最初采用 Plackett-Burman 筛选实验来评估多个设计特征，以预测对升华速率有统计学显著影响的特征。测量了具有故意标称和极端尺寸的小瓶的升华速率，并使用保守和激进的冷冻干燥参数将其与玻璃小瓶设计特征直接相关联，以放大速率的细微差异。使用 USP 纯化水来缓解赋形剂和药物物质存在对质量传递的抑制作用。进一步的研究量化了底部凹陷对升华速率的影响，同时使用模型制剂说明处理结晶和无定形物质的影响。
Plackett-Burman 统计筛选实验的结果表明，升华速率受玻璃类型、小瓶直径、底部半径和填充体积的影响。进一步研究的结果证实，凹陷对升华速率的影响在统计学上并不显著。
Plackett-Burman 筛选实验的结果反映出小瓶直径对升华速率的影响最大。进一步的研究证实，各种底部凹陷不会显著影响升华速率。
