Nucleation phenomena in amorphous sucrose systems

Scoik, Kurt G. Van; Carstensen, J.T.

doi:10.1016/0378-5173(90)90194-9

Cited by 48 publications

(26 citation statements)

References 11 publications

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“…The inhibition of sucrose crystallization in a condensed phase by the presence of other additives has also been reported. 4,11,22 Zografi and co-workers 4 showed that the inhibition of sucrose crystallization, at least in part, can be due to a change in mobility by increases in T g caused by selected additives. For example, T g increased from 74 to 82°C in dry conditions by adding 50% (w/w) lactose.…”

Section: Resultsmentioning

confidence: 98%

Effects of Bovine Somatotropin (rbSt) Concentration at Different Moisture Levels on the Physical Stability of Sucrose in Freeze-Dried rbSt/Sucrose Mixtures

Sarciaux¹,

Hageman²

1997

Journal of Pharmaceutical Sciences

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The inherent instability of many proteins during freeze-drying and storage necessitates the addition of excipients to protect the proteins. It is emphasized in the literature that lyophilized sugar/protein composites should be stored at temperatures below their glass transition temperature (T(g)) to prevent crystallization of excipients. The influence of bovine somatotropin (rbSt) concentration on inhibition of sucrose crystallization at different relative humidities (RH) was of interest. Thermally modulated differential scanning calorimetry (MDSC) was used to measure T(g) and sucrose crystallization temperatures (T(c)) of the composites. Sorption isotherms of the various sucrose/rbSt mixtures were determined gravimetrically with a controlled atmosphere microbalance (CAM) and verified by Karl Fischer analysis of selected samples. The CAM was also used to determine lag times and sucrose crystal growth rates by monitoring weight losses resulting from water liberation upon crystallization of sucrose at 23 degrees C. Results obtained by MDSC indicate that the T(c) increased linearly from approximately 110 degrees C for pure sucrose to approximately 140 degrees C with 20% rbSt at very low water content (<0.1%). Similarly, at 22% RH (4.4% H2O), T(c) increased from approximately 70 degrees C to 120 degrees C. In neither case was T(g) impacted significantly by increasing protein from 0 to 20%. No T(c) could be noted for samples with > or = 30% rbSt in nonisothermal conditions. Plasticization by water decreased both T(g) and T(c) quite similarly but didn't impact the noted effect of protein on T(c). Induction time for sucrose crystallization (i.e. nucleation) at approximately 45% RH (23 degrees C) increased almost 10-fold by addition of 10% rbSt, whereas rates of water loss due to crystallization decreased by no more than 2-3-fold. The overall results strongly indicate that formulations of higher protein concentration will be more resistant to sucrose crystallization and thus more robust when transiently exposed to storage temperatures above their T(g).

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Section: Resultsmentioning

confidence: 98%

Effects of Bovine Somatotropin (rbSt) Concentration at Different Moisture Levels on the Physical Stability of Sucrose in Freeze-Dried rbSt/Sucrose Mixtures

Sarciaux¹,

Hageman²

1997

Journal of Pharmaceutical Sciences

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“…An amorphous sugar matrix prepared by freeze-drying contains numerous pores that had formerly been occupied by ice crystals (Imamura et al, 2010;van Scoik and Carstensen, 1990). The pores in the freeze-dried sugar matrix were found to be markedly diminished as the result of compression at 443 MPa for 5 min in our previous study (Imamura et al, 2010).…”

Section: Enthalpy Relaxationmentioning

confidence: 97%

Influence of compression on water sorption, glass transition, and enthalpy relaxation behavior of freeze-dried amorphous sugar matrices

Imamura

Kagotani

Nomura

et al. 2011

International Journal of Pharmaceutics

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“…The powder X-ray pattern indicated that the sample was highly crystalline. Water sorption experiments in an automated vapor sorption apparatus (DVS-1000, Surface Measurement Systems, London, UK) did not reveal detectable weight gain over the relative humidity (RH) range of 5 to 35%, indicating that the sample was completely crystalline (12,21,22).…”

Section: Preparation Of Crystalline Sucrosementioning

confidence: 99%

Quantification of Crystallinity in Substantially Amorphous Materials by Synchrotron X-ray Powder Diffractometry

2005

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Purpose. The aim of this study was to develop a highly sensitive powder X-ray diffraction (XRD) technique for quantification of crystallinity in substantially amorphous pharmaceuticals, utilizing synchrotron radiation and a 2-D area detector. Methods. Diffraction data were acquired at the European Synchrotron Radiation Facility (France) using a 2-D charge-coupled device detector. The crystallization of amorphous sucrose was monitored in situ, isothermally at several temperatures in the range of 90 to 160-C. An algorithm was developed for separation of the crystalline and amorphous intensities from the total diffraction pattern. Results. The synchrotron XRD technique allowed powder diffraction patterns to be recorded with a time resolution of 40 ms. The gradual crystallization of sucrose is analogous to a series of physical mixtures with increasing content of the crystalline component. The in situ crystallization approach circumvented the problem of inhomogeneity in mixingVa potentially serious issue at extreme mixture compositions. The estimated limit of detection of crystalline sucrose in an amorphous matrix was 0.2% w/w, a considerable improvement over the reported value of õ1% w/w with a conventional XRD. Conclusion. High-intensity XRD can discern subtle changes in the lattice order of materials. The first evidence of crystallization can serve as an indicator of the potential physical instability of the product.

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Nucleation phenomena in amorphous sucrose systems

Cited by 48 publications

References 11 publications

Effects of Bovine Somatotropin (rbSt) Concentration at Different Moisture Levels on the Physical Stability of Sucrose in Freeze-Dried rbSt/Sucrose Mixtures

Effects of Bovine Somatotropin (rbSt) Concentration at Different Moisture Levels on the Physical Stability of Sucrose in Freeze-Dried rbSt/Sucrose Mixtures

Influence of compression on water sorption, glass transition, and enthalpy relaxation behavior of freeze-dried amorphous sugar matrices

Quantification of Crystallinity in Substantially Amorphous Materials by Synchrotron X-ray Powder Diffractometry

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