Water sorption behavior of lyophilized protein–sugar systems and implications for solid-state interactions

Costantino, Henry R.

doi:10.1016/s0378-5173(98)00050-7

Cited by 91 publications

(84 citation statements)

References 21 publications

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“…This discrepancy suggests the potential presence of a drug-excipient interaction similar to that reported by Costantino et al 6 The presence of CNK-20402 likely hinders or delays the recrystallization process of lactose. This hypothesis is confirmed from the vapor sorption curve of colyophilized CNK-20402-lactose (1:10) samples.…”

Section: E47mentioning

confidence: 38%

The protective effect of lactose on lyophilization of CNK-20402

et al. 2005

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The goal of this research was to assess the feasibility of using lyophilization to stabilize an exploratory compound, CNK-20402, with a minimal amount of impurity (CNK-20193) formation. A mixed-level full factorial experimental design was used to screen excipients of glycine, mannitol, lactose monohydrate, and povidone K-12. Cryostage microscopy, powder X-ray diffraction, Karl Fischer titration, HPLC, and water vapor sorption were used to assess the formulationsÕ physicochemical properties and stability. Initial physical characterization from powder X-ray diffraction revealed that the mannitol-and glycine-containing formulations were crystalline with the patterns of the pure excipient, whereas the remaining formulations were amorphous in structure. Chemically, the formulations stored at 50°C for 1 month had 2.36%, 1.05%, 0.81%, 0.79%, and 0.49% CNK-20193 for glycine, mannitol, drug alone, povidone K-12, and lactose formulations, respectively. The formulations containing drug-mannitol, drug alone, and druglactose were selected for accelerated stability study based on statistical analysis. Recovery of CNK-20193 in these formulations was 1.22%, 1.00%, and 0.55%, respectively, when stored at 40°C/75% relative humidity storage conditions for 3 months. Water vapor sorption analysis revealed weight gains of over 7%, 21%, and 24% for the mannitol, lactose, and drug alone formulations, respectively. Testing formulations with different concentrations of lactose by water vapor sorption indicated that CNK-20402 concentrations as low as 10% (wt/wt) could inhibit the recrystallization of lactose. The lactose-containing formulation exhibited the best stability among the formulations tested. The protective mechanism of lactose on the CNK-20402, based on water vapor sorption studies, is believed to be a result of (1) the drug-lactose interaction, and (2) competition between lactose and drug for the residual water in the formulation.

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Section: E47mentioning

confidence: 38%

The protective effect of lactose on lyophilization of CNK-20402

et al. 2005

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“…Pure trehalose crystallized with the formation of trehalose dihydrate [36,42], as can be derived from the constant water content during the desorption phase (Fig. 1).…”

Section: Discussionmentioning

confidence: 87%

“…Several authors have used PVP to stabilize the amorphous state and explained this effect by limiting the molecular mobility in the system due to the addition of high molecular weight molecules [27][28][29]. Proteins have been described to limit the molecular mobility of sugars and prevent crystal nucleation and growth due to strong hydrogen bonds between protein and sugar [24,42,43].…”

Section: Discussionmentioning

confidence: 99%

Spray drying of an attenuated live Newcastle disease vaccine virus intended for respiratory mass vaccination of poultry

Corbanie

Remon

Reeth

et al. 2007

Vaccine

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A powder vaccine intended for aerosol vaccination of poultry was formulated by spray drying a live attenuated Newcastle disease virus with potential stabilizers (mannitol, trehalose, polyvinylpyrrollidone (PVP), bovine serum albumin (BSA)). Thermodynamic properties, water sorption, particle size distribution, nebulization properties, density and morphology of the powders were evaluated and the virus survival during spray drying and storage was determined by incubation in embryonated eggs and subsequent haemagglutination assay. All powders had a narrow size distribution with a median volume diameter of ±30 m (suitable for primary respiratory vaccination of chickens) and good aerosolization characteristics. Four amorphous, hygroscopic formulations were produced (trehalose, trehalose-PVP, trehalose-BSA, trehalose-PVP-BSA), where addition of BSA was beneficial for virus survival during production and storage at 6 and 25 • C. A crystalline, non-hygroscopic powder (mannitol) had a lower stabilizing capacity during production but maintained the remaining virus titre during storage. In conclusion, the study demonstrates that it is possible to produce a dry powder formulation of an attenuated live vaccine for mass vaccination of poultry in a one-step spray drying process.

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“…Costantino et al [6] showed that interaction between proteins and lactose modify lactose crystallization kinetics. In addition, lactose is known to have an efficient cryo-protector due to lactose-protein hydrogen bonds, which could also act to reduce crystallization kinetics [1].…”

Section: Introductionmentioning

confidence: 99%

Study of lactose / β-lactoglobulin interactions during storage

Thomas

Scher

Desobry

2005

Lait

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-The objective of this study was to evaluate the interactions between lactose and β-lactoglobulin in β-lactoglobulin/lactose powders (BL powders) during storage. Model BL powders were produced by co-lyophilization of lactose with increasing quantities of β-lactoglobulin. Lyophilization produced lactose in the amorphous state, which is highly reactive and likely leads to agglomeration of industrial whey powders. The BL powders were stored at 20 ± 1 °C from 0.11 to 0.95 a w and their water sorption behaviour was studied gravimetrically. Before storage, BL powders were amorphous. After storage at high a w , a loss of water was observed on the moisture sorption isotherms of BL powders due to lactose crystals formation, detected by DSC and SEM analysis, and to the structural collapse of the powders. Lactose crystallization occurred at a w = 0.43 in pure lactose samples and at a w = 0.59 in BL powders containing 40% β-lactoglobulin. Moreover, β-lactoglobulin was responsible for a delayed crystallization process in BL powders. Thus, the water sorption behaviour of BL powders was very different from the behaviour of the two compounds mixed after separate lyophilization (B+L powders). These results pointed out interactions between lactose and β-lactoglobulin, which occurred during the lyophilization process and storage. Lactose/β-lactoglobulin interactions stabilized the BL powders against lactose crystallization. In the last part of the work, the nature of the interactions (covalent links, H bonds and hydrophobic links) and the kinetic aspect of the crystallization were studied. whey powder / lactose / β-lactoglobulin / interaction / storage Résumé -Étude des interactions lactose/β-lactoglobuline lors de la conservation. Les poudres obtenues à partir de lactosérum sont très souvent utilisées comme ingrédients alimentaires car elles possèdent d'intéressantes propriétés fonctionnelles (moussantes, gélifiantes…). Lors de la conservation de ces poudres, de nombreuses dégradations biologiques et physico-chimiques altèrent les propriétés fonctionnelles des produits, ainsi que les propriétés physiques et l'aspect des poudres (écoulement, couleur…). La stabilité de ces poudres dépend également fortement de la température de conservation ainsi que de l'activité de l'eau (a w ) et de la composition des produits. Des poudres modèles ont été préparées par co-lyophilisation de lactose avec des quantités croissantes (10 à 40 %) de β-lactoglobuline (poudres BL). Les poudres ont été conservées 3 mois à 20 ± 1 °C, à des activités de l'eau comprises entre 0,11 et 0,95. L'objectif de notre étude a été d'évaluer la présence ou l'absence d'interactions entre lactose et β-lactoglobuline lors de la conservation des poudres, en considérant le comportement de sorption d'eau de ces poudres. Les courbes isothermes de sorption d'eau des poudres BL ont été établies. Elles indiquent que toutes les poudres contenant du lactose libèrent de l'eau, mais à des a w différentes selon la teneur en β-lactoglobuline : à a w = 0,43 pour le lactose, à ...

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Water sorption behavior of lyophilized protein–sugar systems and implications for solid-state interactions

Cited by 91 publications

References 21 publications

The protective effect of lactose on lyophilization of CNK-20402

The protective effect of lactose on lyophilization of CNK-20402

Spray drying of an attenuated live Newcastle disease vaccine virus intended for respiratory mass vaccination of poultry

Study of lactose / β-lactoglobulin interactions during storage

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