Investigations into the stabilisation of drugs by sugar glasses: II

Investigating variables and mechanisms that influence protein integrity in low water content amorphous carbohydrate matrices

“…Also, the linking of formulation to activity is not common. 5,11,36 There was an obvious change in lytic activity only in those lysozyme samples formulated in pH 6.2 buffer and heated for 24 h at 90 C (Table 2). However, here we have shown that while changes in activity are not always measurable (Table 2), there may be chemical modification to the protein (Table 3) occurring that could potentially lead to changes in the antigenicity of the protein.…”

“…10 Drying is achieved by processes such as spray drying or freeze-drying. The mechanism by which this strategy prevents modification is thought to be the result of vitrification of the protein-carbohydrate mixture which, during freeze-drying, allows the formation of a readily dried open-pored cake 11 and subsequently, during storage, retards molecular motion and arrests chemical reaction on a practical timescale. A further application of the glassy state is protein stabilization during antiviral dry heat treatments.…”

Forced Degradation of Therapeutic Proteins

“…During freezing and thawing, proteins are exposed to a combination of stress factors,62 including interfacial stresses (protein/ice surface),63–66 temperature fluctuations,67 cryoconcentration,64 crystallization of excipients,68–70 phase separation,71,72 and pH shifts 65,73–78. The relative importance of each of these factors with respect to protein instability depends on the protein, the formulation, and the freeze–thaw process, and thus needs to be evaluated on a case‐by‐case basis.…”

Advance Understanding of Buffer Behavior during Lyophilization

“…Similar to histidine, the pH of Tris-HCl buffer increases by one pH unit from 7.4 to 8.5 upon freezing to − 30 °C. However, some pH indicator studies have shown no pH change for 10 mM Tris buffer pH 7.4 up to − 40 °C [13] and moderate decrease in pH during freezing of pH 9.8 [14]. Furthermore, by DSC, Tris buffer crystallization was observed during freezing or warming/annealing [10].…”