Application of a mixture DOE for the prediction of formulation critical temperatures during lyophilisation process optimisation

Gervasi, Valeria; Cullen, Sean P.; McCoy, Timothy R.; Crean, Abina M.; Vučen, Sonja

doi:10.1016/j.ijpharm.2019.118807

Cited by 6 publications

(2 citation statements)

References 43 publications

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“…Freeze-drying is widely used to stabilize labile biological medicines and diagnostics; however, formulation can be critical to ensure maximal preservation of activity and stability ( Hubbard et al, 2007 ). Formulation choices also influence the success of the freeze-drying process and can greatly influence the length and hence affordability of freeze-drying processes ( Gervasi et al, 2019 ; Haueser et al, 2020 ). Many articles have described the selection processes, and general guidelines have been published ( Carpenter et al, 1997 ; Carpenter et al, 2002 ; Coxon et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

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Formulation is critical to successful delivery of lyophilized biologics. We have compared the impact of buffer choice and the addition of sodium chloride (a formulant often viewed as unfavorable for freeze-drying applications) on the outcome of trial lyophilization of an interleukin-6 reference material. While phosphate buffer was a preferred choice and yielded well-formed cakes associated with fair recovery of biological activity, the resultant residual moisture content was high (2–4% w/w). By inclusion of isotonic levels of NaCl, the freeze-dried appearance and process were not impaired, but the residual moisture delivered was considerably reduced to levels <1% w/w. We postulate that this is due to the presence of a more open-cake structure and support this with evidence from thermal analysis and scanning electron microscopy. This work illustrates the importance of wide ranging empirical investigation of formulation options in order to optimize freeze-drying outcomes for biologics.

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Section: Introductionmentioning

confidence: 99%

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

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“…Based on a conducted risk assessment included different formulation related variables (risk assessment table is included in supplementary material ), contents of four excipients (sucrose, sodium starch glycolate, lactose monohydrate and avicel Ph 101) were determined as potential predictor variables for optimization of comparative dissolution profile. A mixture design model ( Gervasi et al, 2019 ) was performed using Design Expert software (Version 10.0.0. Stat-Ease), modifying contents of the selected excipients.…”

Section: Methodsmentioning

confidence: 99%

Industrial application of QbD and NIR chemometric models in quality improvement of immediate release tablets

Ramadan

Basalious

Abdallah

2021

Saudi Pharmaceutical Journal

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Quality by Design (QbD) and chemometric models are different sides of the same coin. While QbD models utilize experimentally designed settings for optimization of some quality attributes, these settings can also be utilized for chemometric prediction of the same attributes. We aimed to synchronize optimization of comparative dissolution results of carvedilol immediate release tablets with chemometric prediction of dissolution profile and content uniformity of the product. As an industrial application, selection of variables for optimization was done by performing risk assessment utilizing the archived product records at the pharmaceutical site. Experimental tablets were produced with 20 different settings with the variables being contents of sucrose, sodium starch glycolate, lactose monohydrate, and avicel Ph 101. Contents of the excipients were modelled with F1 dissimilarity factor and F2 similarity factor in HCL, acetate, and USP dissolution media to determine the design space. We initiatively utilized Partial Least Square based Structural Equation Modelling (PLS-SEM) to explore how the excipients and their NIR records explained dissolution of the product. Finally, the optimized formula was utilized with varied content of carvedilol for chemometric prediction of the content uniformity.

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Stabilizers and their interaction with formulation components in frozen and freeze-dried protein formulations

Thakral

Sonje

Munjal

et al. 2021

Advanced Drug Delivery Reviews

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Application of a mixture DOE for the prediction of formulation critical temperatures during lyophilisation process optimisation

Cited by 6 publications

References 43 publications

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Industrial application of QbD and NIR chemometric models in quality improvement of immediate release tablets

Stabilizers and their interaction with formulation components in frozen and freeze-dried protein formulations

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