|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|172578||458549||2013||9 صفحه PDF||سفارش دهید||دانلود رایگان|
• Aggregation data following lyophilization is presented for 15 proteins each with 5 different excipients.
• Descriptor selection methods were used to select from computational aggregation prediction descriptors and biophysical descriptors.
• Correlations were obtained with good fits to experimental data and high predictive power.
• Descriptors selected varied on an excipient-by-excipient basis.
• Results show that descriptors used for solution can also be useful in lyophilized systems.
Lyophilization can induce aggregation in therapeutic proteins, but the relative importance of protein structure, formulation and processing conditions are poorly understood. To evaluate the contribution of protein structure to lyophilization-induced aggregation, fifteen proteins were co-lyophilized with each of five excipients. Extent of aggregation following lyophilization, measured using size-exclusion chromatography, was correlated with computational and biophysical protein structural descriptors via multiple linear regression. Descriptor selection was performed using exhaustive search and forward selection. The results demonstrate that, for a given excipient, extent of aggregation is highly correlated by eight to twelve structural descriptors. Leave-one-out cross validation showed that the correlations were able to successfully predict the aggregation for a protein “left out” of the data set. Selected descriptors varied with excipient, indicating both protein structure and excipient type contribute to lyophilization-induced aggregation. The results show some descriptors used to predict protein aggregation in solution are useful in predicting lyophilized protein aggregation.
Journal: Computers & Chemical Engineering - Volume 58, 11 November 2013, Pages 369–377