Design of a Formulation for Freeze Drying

Jameel, Feroz; Pikal, Mike J.

doi:10.1002/9780470595886.ch18

Cited by 13 publications

(12 citation statements)

References 61 publications

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“…It is well known that biopharmaceuticals can be destabilized during a drying process [14]. Sophisticated chemical formulations and drying protocols have been developed to protect these sensitive compounds during drying by lyophilization and other methods.…”

Section: Introductionmentioning

confidence: 99%

Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles

Choi

Bondy

Yoo

et al. 2013

Journal of Controlled Release

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Immunization using a microneedle patch coated with vaccine offers the promise of simplified vaccination logistics and increased vaccine immunogenicity. This study examined the stability of influenza vaccine during the microneedle coating process, with a focus on the role of coating formulation excipients. Thick, uniform coatings were obtained using coating formulations containing a viscosity enhancer and surfactant, but these formulations retained little functional vaccine hemagglutinin (HA) activity after coating. Vaccine coating in a trehalose-only formulation retained about 40 – 50% of vaccine activity, which is a significant improvement. The partial viral activity loss observed in the trehalose-only formulation was hypothesized to come from osmotic pressure-induced vaccine destabilization. We found that inclusion of a viscosity enhancer, carboxymethyl cellulose, overcame this effect and retained full vaccine activity on both washed and plasma-cleaned titanium surfaces. The addition of polymeric surfactant, Lutrol® micro 68, to the trehalose formulation generated phase transformations of the vaccine coating, such as crystallization and phase separation, which was correlated to additional vaccine activity loss, especially when coating on hydrophilic, plasma-cleaned titanium. Again, the addition of a viscosity enhancer suppressed the surfactant-induced phase transformations during drying, which was confirmed by in vivo assessment of antibody response and survival rate after immunization in mice. We conclude that trehalose and a viscosity enhancer are beneficial coating excipients, but the inclusion of surfactant is detrimental to vaccine stability.

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Section: Introductionmentioning

confidence: 99%

Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles

Choi

Bondy

Yoo

et al. 2013

Journal of Controlled Release

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“…Smaller pores cause higher resistance to water vapor flow, thus decreasing the sublimation rate, increasing the primary drying time and rendering the process less efficient. This phenomenon is also referred to as dried layer resistance [63,67,68,69,70].…”

Section: Key Termmentioning

confidence: 97%

“…Secondary drying reduces the moisture levels to 1-2% or less. The idea underlying this process is that reducing the water content further will improve the storage stability of proteins [63,69]. However, caution must be applied because in secondary drying, while attempting to remove bound water, it is possible that hydrogen bond imbalances can be introduced and/or the native protein conformation disturbed.…”

Section: Key Termmentioning

confidence: 98%

“…Protein formulations are often freeze-dried since it is frequently not possible to prepare stable ready-to-use liquid formulations. Though freezedrying is considered to be an expensive process, it has several advantages in that it does not require a terminal sterilization step, maintains a particle-free state much more easily than other methods, can be relatively easily scaled up and has high recovery yields [63]. Although liquid dosage forms of proteins in ready-to-use syringes are desirable because they avoid the need for reconstitution and are more easy to administer to the patient, currently many proteins in liquid formulations are susceptible to hydrolysis-mediated loss of tertiary structure during storage [27].…”

Section: Freeze-dryingmentioning

confidence: 99%

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Solid-state Protein Formulations

et al. 2015

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When formulated as liquid dosage forms, therapeutic proteins and peptides often show instability during handling as a result of chemical degradation. Solid formulations are frequently required to maintain protein stability during storage, transport and upon administration. Herein we highlight current strategies used to formulate pharmaceutical proteins in the solid form. An overview of the physical instabilities which can arise with proteins is first described. The key solidification techniques of crystallization, freeze-drying and particle forming technologies are then discussed. Examples of current commercial products that are formulated in the solid state are provided and include neutral protamine Hagedorn - insulin crystal suspensions, freeze-dried monoclonal antibodies and leuproride polylactide-co-glycolide microparticles. Finally, future perspectives in solid-state protein formulation are described.

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“…Designing the appropriate manufacturing process is of great importance for the quality of the final drug product. This emerges from the fact that during the fill and finish operations the molecule is subjected to shear forces and air/liquid interfaces which may lead to degradation [ 122 ]. The contact with incompatible solid/liquid interfaces is another potential risk factor during drug product manufacturing.…”

Section: Application Of the Qcm In Drug Product Manufacturing Procmentioning

confidence: 99%

Application of QCM in Peptide and Protein-Based Drug Product Development

2020

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AT-cut quartz crystals vibrating in the thickness-shear mode (TSM), especially quartz crystal resonators (QCRs), are well known as very efficient mass sensitive systems because of their sensitivity, accuracy, and biofunctionalization capacity. They are highly reliable in the measurement of the mass of deposited samples, in both gas and liquid matrices. Moreover, they offer real-time monitoring, as well as relatively low production and operation costs. These features make mass sensitive systems applicable in a wide range of different applications, including studies on protein and peptide primary packaging, formulation, and drug product manufacturing process development. This review summarizes the information on some particular implementations of quartz crystal microbalance (QCM) instruments in protein and peptide drug product development as well as their future prospects.

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Design of a Formulation for Freeze Drying

Cited by 13 publications

References 61 publications

Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles

Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles

Solid-state Protein Formulations

Application of QCM in Peptide and Protein-Based Drug Product Development

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